European Union | Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Posts Tagged ‘European Union’

Global Alliance for Genomics and Health Issues Guidelines for Data Siloing and Sharing

Posted in Advanced Computing Platform, and Bioethics, Artificial Intelligence - Breakthroughs in Theories and Technologies, Artificial Intelligence Applications in Health Care, Big Data, Bio-Ethics, BioBanking, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biotechnology, Genome Biology, Health Economics and Outcomes Research, Health Law & Patient Safety, Health Law Policy, Intelligent Information Systems, Machine Learning, Personalized and Precision Medicine & Genomic Research, Personalized Medicine Coalition, tagged @science 2_0, Big data, biomedical, Cancer - General, curated database, data networks, data silos, European Union, GA4GH, Genomic data, genomics, NGS, Open data, scientific collaboration on December 14, 2021| Leave a Comment »

Reporter: Stephen J. Williams, Ph.D.

From: Heidi Rheim et al. GA4GH: International policies and standards for data sharing across genomic research and healthcare. (2021): Cell Genomics, Volume 1 Issue 2.

Source: DOI:https://doi.org/10.1016/j.xgen.2021.100029

Highlights

Siloing genomic data in institutions/jurisdictions limits learning and knowledge
GA4GH policy frameworks enable responsible genomic data sharing
GA4GH technical standards ensure interoperability, broad access, and global benefits
Data sharing across research and healthcare will extend the potential of genomics

Summary

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

The GA4GH organization and its strategies for addressing challenges of clinical and genomic #dataSharing https://t.co/a61HVLiKyD pic.twitter.com/ngdwecwEcd
— NCI Genomics (@NCIgenomics) November 17, 2021

In order for genomic and personalized medicine to come to fruition it is imperative that data siloes around the world are broken down, allowing the international collaboration for the collection, storage, transferring, accessing and analying of molecular and health-related data.

We had talked on this site in numerous articles about the problems data siloes produce. By data siloes we are meaning that collection and storage of not only DATA but intellectual thought are being held behind physical, electronic, and intellectual walls and inacessible to other scientisits not belonging either to a particular institituion or even a collaborative network.

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

Standardization and harmonization of data is key to this effort to sharing electronic records. The EU has taken bold action in this matter. The following section is about the General Data Protection Regulation of the EU and can be found at the following link:

https://ec.europa.eu/info/law/law-topic/data-protection/data-protection-eu_en

Fundamental rights

The EU Charter of Fundamental Rights stipulates that EU citizens have the right to protection of their personal data.

Protection of personal data

Legislation

The data protection package adopted in May 2016 aims at making Europe fit for the digital age. More than 90% of Europeans say they want the same data protection rights across the EU and regardless of where their data is processed.

The General Data Protection Regulation (GDPR)

Regulation (EU) 2016/679 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data. This text includes the corrigendum published in the OJEU of 23 May 2018.

The regulation is an essential step to strengthen individuals’ fundamental rights in the digital age and facilitate business by clarifying rules for companies and public bodies in the digital single market. A single law will also do away with the current fragmentation in different national systems and unnecessary administrative burdens.

The regulation entered into force on 24 May 2016 and applies since 25 May 2018. More information for companies and individuals.

Information about the incorporation of the General Data Protection Regulation (GDPR) into the EEA Agreement.

EU Member States notifications to the European Commission under the GDPR

The Data Protection Law Enforcement Directive

Directive (EU) 2016/680 on the protection of natural persons regarding processing of personal data connected with criminal offences or the execution of criminal penalties, and on the free movement of such data.

The directive protects citizens’ fundamental right to data protection whenever personal data is used by criminal law enforcement authorities for law enforcement purposes. It will in particular ensure that the personal data of victims, witnesses, and suspects of crime are duly protected and will facilitate cross-border cooperation in the fight against crime and terrorism.

The directive entered into force on 5 May 2016 and EU countries had to transpose it into their national law by 6 May 2018.

The following paper by the organiztion The Global Alliance for Genomics and Health discusses these types of collaborative efforts to break down data silos in personalized medicine. This organization has over 2000 subscribers in over 90 countries encompassing over 60 organizations.

Enabling responsible genomic data sharing for the benefit of human health

The Global Alliance for Genomics and Health (GA4GH) is a policy-framing and technical standards-setting organization, seeking to enable responsible genomic data sharing within a human rights framework.

he Global Alliance for Genomics and Health (GA4GH) is an international, nonprofit alliance formed in 2013 to accelerate the potential of research and medicine to advance human health. Bringing together 600+ leading organizations working in healthcare, research, patient advocacy, life science, and information technology, the GA4GH community is working together to create frameworks and standards to enable the responsible, voluntary, and secure sharing of genomic and health-related data. All of our work builds upon the Framework for Responsible Sharing of Genomic and Health-Related Data.

GA4GH Connect is a five-year strategic plan that aims to drive uptake of standards and frameworks for genomic data sharing within the research and healthcare communities in order to enable responsible sharing of clinical-grade genomic data by 2022. GA4GH Connect links our Work Streams with Driver Projects—real-world genomic data initiatives that help guide our development efforts and pilot our tools.

From the article on Cell Genomics GA4GH: International policies and standards for data sharing across genomic research and healthcare

Source: Open Access DOI:https://doi.org/10.1016/j.xgen.2021.100029PlumX Metrics

The Global Alliance for Genomics and Health (GA4GH) is a worldwide alliance of genomics researchers, data scientists, healthcare practitioners, and other stakeholders. We are collaborating to establish policy frameworks and technical standards for responsible, international sharing of genomic and other molecular data as well as related health data. Founded in 2013,³ the GA4GH community now consists of more than 1,000 individuals across more than 90 countries working together to enable broad sharing that transcends the boundaries of any single institution or country (see https://www.ga4gh.org).In this perspective, we present the strategic goals of GA4GH and detail current strategies and operational approaches to enable responsible sharing of clinical and genomic data, through both harmonized data aggregation and federated approaches, to advance genomic medicine and research. We describe technical and policy development activities of the eight GA4GH Work Streams and implementation activities across 24 real-world genomic data initiatives (“Driver Projects”). We review how GA4GH is addressing the major areas in which genomics is currently deployed including rare disease, common disease, cancer, and infectious disease. Finally, we describe differences between genomic sequence data that are generated for research versus healthcare purposes, and define strategies for meeting the unique challenges of responsibly enabling access to data acquired in the clinical setting.

GA4GH organization

GA4GH has partnered with 24 real-world genomic data initiatives (Driver Projects) to ensure its standards are fit for purpose and driven by real-world needs. Driver Projects make a commitment to help guide GA4GH development efforts and pilot GA4GH standards (see Table 2). Each Driver Project is expected to dedicate at least two full-time equivalents to GA4GH standards development, which takes place in the context of GA4GH Work Streams (see Figure 1). Work Streams are the key production teams of GA4GH, tackling challenges in eight distinct areas across the data life cycle (see Box 1). Work Streams consist of experts from their respective sub-disciplines and include membership from Driver Projects as well as hundreds of other organizations across the international genomics and health community.

Figure thumbnail gr1 — **Figure 1**Matrix structure of the Global Alliance for Genomics and HealthShow full caption

Box 1GA4GH Work Stream focus areasThe GA4GH Work Streams are the key production teams of the organization. Each tackles a specific area in the data life cycle, as described below (URLs listed in the web resources).

(1)Data use & researcher identities: Develops ontologies and data models to streamline global access to datasets generated in any country^9,10
(2)Genomic knowledge standards: Develops specifications and data models for exchanging genomic variant observations and knowledge¹⁸
(3)Cloud: Develops federated analysis approaches to support the statistical rigor needed to learn from large datasets
(4)Data privacy & security: Develops guidelines and recommendations to ensure identifiable genomic and phenotypic data remain appropriately secure without sacrificing their analytic potential
(5)Regulatory & ethics: Develops policies and recommendations for ensuring individual-level data are interoperable with existing norms and follow core ethical principles
(6)Discovery: Develops data models and APIs to make data findable, accessible, interoperable, and reusable (FAIR)
(7)Clinical & phenotypic data capture & exchange: Develops data models to ensure genomic data is most impactful through rich metadata collected in a standardized way
(8)Large-scale genomics: Develops APIs and file formats to ensure harmonized technological platforms can support large-scale computing

For more articles on Open Access, Science 2.0, and Data Networks for Genomics on this Open Access Scientific Journal see:

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

Icelandic Population Genomic Study Results by deCODE Genetics come to Fruition: Curation of Current genomic studies

eScientific Publishing a Case in Point: Evolution of Platform Architecture Methodologies and of Intellectual Property Development (Content Creation by Curation) Business Model

UK Biobank Makes Available 200,000 whole genomes Open Access

Systems Biology Analysis of Transcription Networks, Artificial Intelligence, and High-End Computing Coming to Fruition in Personalized Oncology

Read Full Post »

Multiple Major Scientific Journals Will Fully Adopt Open Access Under Plan S

Posted in Academic Publishing, Curation, Open Access Journals, Scientific Publishing, tagged #openscience, #science2_0, Academic publishing, European Union, JBC, Journal of Biological Chemistry, National Center for Biotechnology Information, Nature, NCBI, Open access, Open access journal, Open Access Online Scientific Journal, Oxford Journals, plan s, PubMed on September 10, 2020| Leave a Comment »

Multiple Major Scientific Journals Will Fully Adopt Open Access Under Plan S

Curator: Stephen J. Williams, PhD

More university library systems have been pressuring major scientific publishing houses to adopt an open access strategy in order to reduce the library system’s budgetary burdens. In fact some major universities like the California system of universities (University of California and other publicly funded universities in the state as well as Oxford University in the UK, even MIT have decided to become their own publishing houses in a concerted effort to fight back against soaring journal subscription costs as well as the costs burdening individual scientists and laboratories (some of the charges to publish one paper can run as high as $8000.00 USD while the journal still retains all the rights of distribution of the information). Therefore more and more universities, as well as concerted efforts by the European Union and the US government are mandating that scientific literature be published in an open access format.

The results of this pressure are evident now as major journals like Nature, JBC, and others have plans to go fully open access in 2021. Below is a listing and news reports of some of these journals plans to undertake a full Open Access Format.

Nature to join open-access Plan S, publisher says

09 APRIL 2020 UPDATE 14 APRIL 2020

Springer Nature says it commits to offering researchers a route to publishing open access in Nature and most Nature-branded journals from 2021.

Richard Van Noorden

After a change in the rules of the bold open-access (OA) initiative known as Plan S, publisher Springer Nature said on 8 April that many of its non-OA journals — including Nature — were now committed to joining the plan, pending discussion of further technical details.

This means that Nature and other Nature-branded journals that publish original research will now look to offer an immediate OA route after January 2021 to scientists who want it, or whose funders require it, a spokesperson says. (Nature is editorially independent of its publisher, Springer Nature.)

“We are delighted that Springer Nature is committed to transitioning its journals to full OA,” said Robert Kiley, head of open research at the London-based biomedical funder Wellcome, and the interim coordinator for Coalition S, a group of research funders that launched Plan S in 2018.

But Lisa Hinchliffe, a librarian at the University of Illinois at Urbana–Champaign, says the changed rules show that publishers have successfully pushed back against Plan S, softening its guidelines and expectations — in particular in the case of hybrid journals, which publish some content openly and keep other papers behind paywalls. “The coalition continues to take actions that rehabilitate hybrid journals into compliance rather than taking the hard line of unacceptability originally promulgated,” she says.

What is Plan S?

The goal of Plan S is to make scientific and scholarly works free to read as soon as they are published. So far, 17 national funders, mostly in Europe, have joined the initiative, as have the World Health Organization and two of the world’s largest private biomedical funders — the Bill & Melinda Gates Foundation and Wellcome. The European Commission will also implement an OA policy that is aligned with Plan S. Together, this covers around 7% of scientific articles worldwide, according to one estimate. A 2019 report published by the publishing-services firm Clarivate Analytics suggested that 35% of the research content published in Nature in 2017 acknowledged a Plan S funder (see ‘Plan S papers’).

PLAN S PAPERS

Journal	Total papers in 2017	% acknowledging Plan S funder
Nature	290	35%
Science	235	31%
Proc. Natl Acad. Sci. USA	639	20%

Source: The Plan S footprint: Implications for the scholarly publishing landscape (Institute for Scientific Information, 2019)

Source: https://www.nature.com/articles/d41586-020-01066-5

Opening ASBMB publications freely to all

Lila M. Gierasch, Editor-in-Chief, Journal of Biological Chemistry,

Nicholas O. Davidson,

Kerry-Anne Rye, Editors-in-Chief, Journal of Lipid Research and

Alma L. Burlingame, Editor-in-Chief, Molecular and Cellular Proteomics

We are extremely excited to announce on behalf of the American Society for Biochemistry and Molecular Biology (ASBMB) that the Journal of Biological Chemistry (JBC), Molecular & Cellular Proteomics (MCP), and the Journal of Lipid Research (JLR) will be published as fully open-access journals beginning in January 2021. This is a landmark decision that will have huge impact for readers and authors. As many of you know, many researchers have called for journals to become open access to facilitate scientific progress, and many funding agencies across the globe are either already requiring or considering a requirement that all scientific publications based on research they support be published in open-access journals. The ASBMB journals have long supported open access, making the accepted author versions of manuscripts immediately and permanently available, allowing authors to opt in to the immediate open publication of the final version of their paper, and endorsing the goals of the larger open-access movement (1). However, we are no longer satisfied with these measures. To live up to our goals as a scientific society, we want to freely distribute the scientific advances published in JBC, MCP, and JLR as widely and quickly as possible to support the scientific community. How better can we facilitate the dissemination of new information than to make our scientific content freely open to all?

For ASBMB journals and others who have contemplated or made the transition to publishing all content open access, achieving this milestone generally requires new financial mechanisms. In the case of the ASBMB journals, the transition to open access is being made possible by a new partnership with Elsevier, whose established capabilities and economies of scale make the costs associated with open-access publication manageable for the ASBMB (2). However, we want to be clear: The ethos of ASBMB journals will not change as a consequence of this new alliance. The journals remain society journals: The journals are owned by the society, and all scientific oversight for the journals will remain with ASBMB and its chosen editors. Peer review will continue to be done by scientists reviewing the work of scientists, carried out by editorial board members and external referees on behalf of the ASBMB journal leadership. There will be no intervention in this process by the publisher.

Although we will be saying “goodbye” to many years of self-publishing (115 in the case of JBC), we are certain that we are taking this big step for all the right reasons. The goal for JBC, MCP, and JLR has always been and will remain to help scientists advance their work by rapidly and effectively disseminating their results to their colleagues and facilitating the discovery of new findings (1, 3), and open access is only one of many innovations and improvements in science publishing that could help the ASBMB journals achieve this goal. We have been held back from fully exploring these options because of the challenges of “keeping the trains running” with self-publication. In addition to allowing ASBMB to offer all the content in its journals to all readers freely and without barriers, the new partnership with Elsevier opens many doors for ASBMB publications, from new technology for manuscript handling and production, to facilitating reader discovery of content, to deploying powerful analytics to link content within and across publications, to new opportunities to improve our peer review mechanisms. We have all dreamed of implementing these innovations and enhancements (4, 5) but have not had the resources or infrastructure needed.

A critical aspect of moving to open access is how this decision impacts the cost to authors. Like most publishers that have made this transition, we have been extremely worried that achieving open-access publishing would place too big a financial burden on our authors. We are pleased to report the article-processing charges (APCs) to publish in ASBMB journals will be on the low end within the range of open-access fees: $2,000 for members and $2,500 for nonmembers. While slightly higher than the cost an author incurs now if the open-access option is not chosen, these APCs are lower than the current charges for open access on our existing platform.

References

1.↵ Gierasch, L. M., Davidson, N. O., Rye, K.-A., and Burlingame, A. L. (2019) For the sake of science. J. Biol. Chem. 294, 2976 FREE Full Text

2.↵ Gierasch, L. M. (2017) On the costs of scientific publishing. J. Biol. Chem. 292, 16395–16396 FREE Full Text

3.↵ Gierasch, L. M. (2020) Faster publication advances your science: The three R’s. J. Biol. Chem. 295, 672 FREE Full Text

4.↵ Gierasch, L. M. (2017) JBC is on a mission to facilitate scientific discovery. J. Biol. Chem. 292, 6853–6854 FREE Full Text

5.↵ Gierasch, L. M. (2017) JBC’s New Year’s resolutions: Check them off! J. Biol. Chem. 292, 21705–21706 FREE Full Text

Source: https://www.jbc.org/content/295/22/7814.short?ssource=mfr&rss=1

Open access publishing under Plan S to start in 2021

BMJ

2019; 365 doi: https://doi.org/10.1136/bmj.l2382 (Published 31 May 2019)Cite this as: BMJ 2019;365:l2382

From 2021, all research funded by public or private grants should be published in open access journals, according to a group of funding agencies called coALition S.1

The plan is the final version of a draft that was put to public consultation last year and attracted 344 responses from institutions, almost half of them from the UK.2 The responses have been considered and some changes made to the new system called Plan S, a briefing at the Science Media Centre in London was told on 29 May.

The main change has been to delay implementation for a year, to 1 January 2021, to allow more time for those involved—researchers, funders, institutions, publishers, and repositories—to make the necessary changes, said John-Arne Røttingen, chief executive of the Research Council of Norway.

“All research contracts signed after that date should include the obligation to publish in an open access journal,” he said. T……

(Please Note in a huge bit of irony this article is NOT Open Access and behind a paywall…. Yes an article about an announcement to go Open Access is not Open Access)

Source: https://www.bmj.com/content/365/bmj.l2382.full

Plan S

From Wikipedia, the free encyclopedia

Jump to navigation Jump to search

Not to be confused with S-Plan.

Plan S is an initiative for open-access science publishing launched in 2018^[1][2] by “cOAlition S”,^[3] a consortium of national research agencies and funders from twelve European countries. The plan requires scientists and researchers who benefit from state-funded research organisations and institutions to publish their work in open repositories or in journals that are available to all by 2021.^[4] The “S” stands for “shock”.^[5]

Principles of the plan[edit]

The plan is structured around ten principles.^[3] The key principle states that by 2021, research funded by public or private grants must be published in open-access journals or platforms, or made immediately available in open access repositories without an embargo. The ten principles are:

authors should retain copyrighton their publications, which must be published under an open license such as Creative Commons;
the members of the coalition should establish robust criteria and requirements for compliant open access journals and platforms;
they should also provide incentives for the creation of compliant open access journals and platforms if they do not yet exist;
publication fees should be covered by the funders or universities, not individual researchers;
such publication fees should be standardized and capped;
universities, research organizations, and libraries should align their policies and strategies;
for books and monographs, the timeline may be extended beyond 2021;
open archives and repositories are acknowledged for their importance;
hybrid open-access journalsare not compliant with the key principle;
members of the coalition should monitor and sanction non-compliance.

Member organisations

Organisations in the coalition behind Plan S include:^[14]

Austria: Austrian Science Fund;
Finland: Academy of Finland;^[15]
France: Agence nationale de la recherche;
Ireland: Science Foundation Ireland;
Italy: Istituto Nazionale di Fisica Nucleare;
Luxembourg: Luxembourger National Research Fund[lb];
Netherlands: Netherlands Organisation for Scientific Research;
Norway: Research Council of Norway;
Poland: National Science Centre;
Slovenia: Slovenian Research Agency[sl];
Sweden: Swedish Research Council for Sustainable Development (Formas)[sv];Swedish Research Council for Health, Working Life and Welfare (Forte);^[14] Vinnova.^[16]
Jordan:^[17]Higher Council for Science and Technology^[18][19]
United Kingdom: United Kingdom Research and Innovation; Wellcome Trust^[20]
United States: Gates Foundation.^[20][21]
Zambia: National Science and Technology Council (NSTC)^[22]

International organizations that are members:

Aligning Science Against Parkinson^[23][24]

Plan S is also supported by:

Real Time Coverage @BIOConvention #BIO2019: Genome Editing and Regulatory Harmonization: Progress and Challenges

Posted in and Bioethics, Biotechnology, Conference Coverage with Social Media, CRISPR applied to Human Germ Line, CRISPR/Cas9 & Gene Editing, FDA, FDA Regulatory Affairs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Gene Editing Impact on Longevity, Gene Therapy & Gene Editing Development, Health Law & Patient Safety, Health Law Policy, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, tagged biosafety and bioethics, CRISPR, CRISPR Biology • Genome Editing • Gene Drives • DNA Repair • Model and Industrial Organisms • Technology Development • Stem Cells/Cancer • Genome-Wide Screens, Duchenne muscular dystrophy, EMA, EUDRA, European Union, FDA, FDA 510(k) clearance, gene editing on June 5, 2019| Leave a Comment »

Real Time Coverage @BIOConvention #BIO2019: Genome Editing and Regulatory Harmonization: Progress and Challenges

Reporter: Stephen J Williams, PhD @StephenJWillia2

Genome editing offers the potential of new and effective treatments for genetic diseases. As companies work to develop these treatments, regulators are focused on ensuring that any such products meet applicable safety and efficacy requirements. This panel will discuss how European Union and United States regulators are approaching therapeutic use of genome editing, issues in harmonization between these two – and other – jurisdictions, challenges faced by industry as regulatory positions evolve, and steps that organizations and companies can take to facilitate approval and continued efforts at harmonization.

Speakers

Emily MardenCounsel Food Drug and Regulatory Life Sciences at Sidley Austin LLP

Gary CharbonneauSenior Vice President of Regulatory Affairs at Sarepta

Dr. Denise GavinActing Gene Therapy Branch Chief, Division of Cell and Gene Therapy at Center for Biologics Evaluation and Research (CBER), FDA

Georgia GavriilidouCounsel, Food, Drug and Medical Device Regulatory Life Sciences at Sidley Austin LLP

Daniel TakefmanSVP and Head of Regulatory Affairs at Spark Therapeutics

CBER: because of the nature of these gene therapies, which are mainly orphan, there is expedited review. Since they started this division in 2015, they have received over 1500 applications.

Spark: Most of the issues were issues with the primary disease not the gene therapy so they had to make new endpoint tests so had talks with FDA before they entered phase III. There has been great collaboration with FDA, now they partnered with Novartis to get approval outside US. You should be willing to partner with EU pharmas to expedite the regulatory process outside US. In China the process is new and Brazil is behind on their gene therapy guidance. However there is the new issue of repeat testing of your manufacturing process, as manufacturing of gene therapies had been small scale before. However he notes that problems with expedited review is tough because you don’t have alot of time to get data together. They were lucky that they had already done a randomized trial.

Sidley Austin: EU regulatory you make application with advance therapy you don’t have a national option, the regulation body assesses a committee to see if has applicability. Then it goes to a safety committee. EU has been quicker to approve these advance therapies. Twenty five percent of their applications are gene therapies. Companies having issues with manufacturing. There can be issues when the final application is formalized after discussions as problems may arise between discussions, preliminary applications, and final applications.

Sarepta: They have a robust gene therapy program. Their lead is a therapy for DMD (Duchenne’s Muscular Dystrophy) where affected males die by 25. Japan and EU have different regulatory applications and although they are similar and data can be transferred there is more paperwork required by EU. The US uses an IND for application. Global feedback is very challenging, they have had multiple meetings around the world and takes a long time preparing a briefing package….. putting a strain on the small biotechs. No company wants to be either just EU centric or US centric they just want to get out to market as fast as possible.

Please follow LIVE on TWITTER using the following @ handles and # hashtags:

@Handles

@pharma_BI

@AVIVA1950

@BIOConvention

# Hashtags

#BIO2019 (official meeting hashtag)

#itstartswithone

#RightMixMatters

Read Full Post »

1:15PM 11/12/2014 – Keynote Speaker – International Genetics Health and Disease @10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

Posted in Academic Publishing, Conference Coverage with Social Media, Personalized and Precision Medicine & Genomic Research, Scientific & Biotech Conferences: Press Coverage, tagged Cancer research, European Union, Health policy, healthcare, healthcare costs, Horizon 2020, Personalized medicine, Spain, Translational Medicine on November 12, 2014| Leave a Comment »

1:15PM 11/12/2014 – 10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

Reporter: Aviva Lev-Ari, PhD, RN

REAL TIME Coverage of this Conference by Dr. Aviva Lev-Ari, PhD, RN – Director and Founder of LEADERS in PHARMACEUTICAL BUSINESS INTELLIGENCE, Boston http://pharmaceuticalintelligence.com

1:15 p.m. – Keynote Speaker – International Genetics Health and Disease

International Genetics Health and Disease

The principles of personalized medicine and how they affect the lives of people acknowledge no national boundaries. Although there are some differences among the diverse populations around the world in terms of their genetic variation, the general principles of personalized medicine apply uniformly across many populations. Dr. Periz will discuss how personalized medicine is viewed across the many European countries with particular emphasis on how Spain is implementing it into its medical care.

Keynote Speaker

Antonio L. Andreu Periz, M.D.
Director, Instituto de Salud Carlos III, Madrid

@insalud_es @CIBER-BBN

Governmental & Public Health National Organization like a combination of CDC and “Hybrid NIH in the US”

Personalized Medicine (PM) in Europe

Europe and Spain — PM is changing Medical Practice, regulations standard of care.

In Europe 28 National systems in Spain alone 17 systems

Implementation of PM in Europe: Hospitals, Regulation,

develop proof of concept
identify mechanisms
bring basic research to clinical
incorporation into a Portfolio of policies on PM

Horizon 2020 in EU – 2016 launch action on PM in various countries in EU

Translational level for all EC members
Coalition of 28 Research Centers in Europe to promote PM
Sharing Databases, Data on HC, infrastructure for Translational research
OMICS
Biomarkers
clinical trials

CSA – Coordination Support Action

PerMed 500,000 Euro for 5 years, 9 operating partners, representatives of Ministry of Health, Israel and Canada Ministry of Health are included
Research Agenda for PM in Europe – SWOT Analysis
Recommendations for UC to start PM in 2016
– basic research
– translation
– ICTs
– Regulatory

SPAIN – Initiatives on PM: Aggregation of Knowledge

One single organization collaborates with 22 Institutions on Biomedical research – Concentration in Barcelona and in Madrid
Projects of Excellence: PhD level Projects – Clinical Practice: Imaging, Endocrinology, genomics, cardiology
2014 — 35 Applicants – not all are on Cancer 25% are in Cancer 75% are in other clinical Fields
12Million Euros will fund 1/4 of the applicants
PhD Thesis on PM – common project 2 yr governmental institute and 2 years in biotech industry

EAPM – Europe Alliance for PM

raise awareness on HOW PM CAN SHAPE Healthcare in Europe: Diagnosis, Treatment,
Specialized Treatment for Europe’s Patient (STEPs) – Five Steps

Global alliances to shape Medical Practice based on PM – Collaboration Industry and Academia

PMC in the US (Personalized Medical Coalition)
PerMEd in Europe (coalition in Europe supporting innovation in personalized medicine)
EAPM (European Alliance for Personalized Medicine)

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx#sthash.qGbGZXXf.dpuf

UPDATED: PLATO Trial on ACS: BRILINTA (ticagrelor) better than Plavix® (clopidogrel bisulfate): Lowering chances of having another heart attack

Posted in Aortic Valve: TAVR, TAVI vs Open Heart Surgery, Cell Biology, Signaling & Cell Circuits, Coagulation Therapy and Internal Bleeding, Disease Biology, Small Molecules in Development of Therapeutic Drugs, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Mitral Valve: Repair and Replacement, Origins of Cardiovascular Disease, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, tagged Adverse effect, American Heart Association, AstraZeneca, Brilinta, Clopidogrel, European Commission, European Union, Food and Drug Administration, myocardial infarction, ST elevation, Ticagrelor on December 28, 2012| 3 Comments »

UPDATED: PLATO Trial on ACS: BRILINTA (ticagrelor) better than Plavix® (clopidogrel bisulfate): Lowering chances of having another heart attack

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 9/1/2019

Extended DAPT with Brilinta: No Benefit for Stable CAD in T2D

Substudy in those with prior PCI might identify group where bleeding tradeoff is worthwhile

PARIS — Ticagrelor (Brilinta) as part of a dual antiplatelet therapy (DAPT) regimen didn’t improve net outcomes for stable coronary artery disease (CAD) among type 2 diabetes patients, except perhaps in the setting of percutaneous coronary intervention (PCI), the THEMIS trial showed.

Adding the potent antiplatelet agent to aspirin reduced cardiovascular (CV) death, myocardial infarction (MI), or stroke (7.7% vs 8.5%, HR 0.90, 95% CI 0.81-0.99), reported Deepak Bhatt, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, at the European Society of Cardiology (ESC) congress and online in the New England Journal of Medicine.

But it also increased

TIMI major bleeding (2.2% vs 1.0%, HR 2.32, 95% CI 1.82-2.94) and

intracranial hemorrhage (0.7% vs 0.5%, HR 1.71, 95% CI 1.18- 2.48) over aspirin alone, albeit

without more fatal bleeding (0.2% vs 0.1%, P=0.11).

The combined effect was neutral for the exploratory composite outcome of “irreversible harm” (death from any cause, MI, stroke, fatal bleeding, or intracranial hemorrhage 10.1% vs 10.8%, HR 0.93, 95% CI 0.86-1.02).

ESC session study discussant Colin Baigent, MD, of Oxford University in England, actually calculated 12 major bleeds for every eight events prevented.

“This is a consistent story: when we add an antiplatelet agent for risk reduction, we increase the risk of bleeding,” noted Richard Kovacs, MD, of Indiana University in Indianapolis and president of the American College of Cardiology.

THEMIS is the final part of a largely-disappointing PARTHENON development program for ticagrelor, he noted. “It hasn’t changed practice. …Will the main THEMIS trial change clinical practice? In my opinion, no.”

Primary Source

New England Journal of Medicine

Source Reference: Steg PG, et al “Ticagrelor in Patients with Stable Coronary Disease and Diabetes” N Engl J Med 2019; DOI: 10.1056/NEJMoa1908077.
Secondary Source

New England Journal of Medicine

Source Reference: Bates ER “Antiplatelet Therapy for Prevention of Cardiovascular Events in Patients with Type-2 Diabetes Mellitus” N Engl J Med 2019; DOI: 10.1056/NEJMe1910813.
Additional Source

The Lancet

Source Reference: Bhatt DL, et al “Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial” Lancet 2019; DOI: 10.1016/S0140-6736(19)31887-2.

SOURCE

https://www.medpagetoday.com/meetingcoverage/esc/81925?xid=nl_mpt_ACC_Reporter_2019-09-01&eun=g5099207d2r

UPDATED on 10/4/2016

Soriot’s $3.5B Brilinta dream is dashed by yet another big trial flop for AstraZeneca

by john carroll
October 4, 2016 09:00 AM EDT
Updated: 09:33 AM

Brilinta, the drug failed to demonstrate a benefit over generic Plavix (clopidogrel) for peripheral artery disease. Back in March, the heart drug flopped in a large stroke study, unable to prove that it could beat aspirin. And Soriot can chalk up those expensive studies to proving Brilinta’s serious deficiencies.

“We don’t believe the goal of $3.5 billion is attainable. I think it would be unrealistic to believe that,” Ludovic Helfgott, head of AstraZeneca’s Brilinta business, told Reuters.

Brilinta brought in a total of $619 million last year after disappointing analysts repeatedly with lower-than-expected quarterly revenue.

Heart studies aren’t cheap. AstraZeneca recruited 13,500 patients for the EUCLID study, and it had enrolled close to that number for the earlier SOCRATES trial.

SOURCE

http://endpts.com/soriots-3-5b-brilinta-dream-is-dashed-by-yet-another-big-trial-flop-for-astrazeneca/?utm_medium=email&utm_campaign=75%20Dinner%20with%20Brent&utm_content=75%20Dinner%20with%20Brent+CID_8008d3b4f16d90576238cceef624d211&utm_source=ENDPOINTS%20emails&utm_term=Soriots%2035B%20Brilinta%20dream%20is%20dashed%20by%20yet%20another%20big%20trial%20flop%20for%20AstraZeneca

UPDATED on 9/4/2014

Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction

Gilles Montalescot, M.D., Ph.D., Arnoud W. van ‘t Hof, M.D., Ph.D., Frédéric Lapostolle, M.D., Ph.D., Johanne Silvain, M.D., Ph.D., Jens Flensted Lassen, M.D., Ph.D., Leonardo Bolognese, M.D., Warren J. Cantor, M.D., Ángel Cequier, M.D., Ph.D., Mohamed Chettibi, M.D., Ph.D., Shaun G. Goodman, M.D., Christopher J. Hammett, M.B., Ch.B., M.D., Kurt Huber, M.D., Magnus Janzon, M.D., Ph.D., Béla Merkely, M.D., Ph.D., Robert F. Storey, M.D., D.M., Uwe Zeymer, M.D., Olivier Stibbe, M.D., Patrick Ecollan, M.D., Wim M.J.M. Heutz, M.D., Eva Swahn, M.D., Ph.D., Jean-Philippe Collet, M.D., Ph.D., Frank F. Willems, M.D., Ph.D., Caroline Baradat, M.Sc., Muriel Licour, M.Sc., Anne Tsatsaris, M.D., Eric Vicaut, M.D., Ph.D., and Christian W. Hamm, M.D., Ph.D. for the ATLANTIC Investigators

September 1, 2014DOI: 10.1056/NEJMoa1407024

BACKGROUND

The direct-acting platelet P2Y₁₂ receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown.

Full Text of Background…

METHODS

We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours’ duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days.

Full Text of Methods…

RESULTS

The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used.

Full Text of Results…

CONCLUSIONS

Prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. (Funded by AstraZeneca; ATLANTIC ClinicalTrials.gov number, NCT01347580.)

SOURCE

http://www.nejm.org/doi/full/10.1056/NEJMoa1407024?query=TOC

UPDATED on 2/7/2014

PLATO Controversy Hits the Wall Street Journal

Michael O’Riordan

February 05, 2014

NEW YORK, NY – The controversy surrounding the PLATOtrial of ticagrelor (Brilinta, AstraZeneca) continues unabated, according to a story published in the Wall Street Journal. Specifically, a sealed complaint filed in US district court in the District of Columbia by a researcher contends that the cardiovascular events in the study “may have been manipulated” ^[1].

Dr Victor Serebruany (HeartDrug Research Laboratories, Johns Hopkins University, Towson, MD), who has long been a thorn in the side of AstraZeneca and the PLATO investigators, filed the complaint under the False Claims Act, reports theWall Street Journal. The Journal notes that the US attorney’s office in Washington, DC, has contacted Serebruany and is currently investigating the clinical trial.As reported by heartwirein October 2013, the US Department of Justice issued a civil investigative demand from its civil division “seeking documents and information regarding PLATO.” AstraZeneca is complying with the request.

First reported by heart wirein 2009 , the PLATO trial was a positive study involving more 18 000 patients from 43 countries. PLATO investigators, led by Dr Lars Wallentin (Uppsala Clinical Research Center, Sweden), showed that treating acute coronary syndrome patients with ticagrelor significantly reduced the rate of MI, stroke, and cardiovascular death compared with patients taking clopidogrel. Results were presented at the European Society of Cardiology 2009 Congress and reported in the New England Journal of Medicine.

PLATO has been dogged by questions, including prior to approval. In the sealed complaint, Serebruany takes issue with a number of things, many of which have been reported previously. He alleges that the

number of clinical events among those taking clopidogrel was high compared with other studies, pointing out that the rate of all-cause death was 5.9% among clopidogrel-treated patients—nearly twice as high as earlier studies. In addition,
the sealed complaint documents the geographic discrepancies in the trial, noting there was a trend toward worse outcomes with ticagrelor at North American sites.The complaint also alleges that
an initial count of clinical events suggested the two drugs were equivalent, but adjudication by the Duke Clinical Research Institute attributed another 45 MIs to the clopidogrel group, which tipped the results in favor of ticagrelor. Other questions raised about the study include
site monitoring and timing of clinical events. Serebruany also alleges that
the trial may have unintentionally been unblinded because of the shape of clopidogrel’s “split capsules,” which would have enabled doctors and nurses to know which drug patients received.

AstraZeneca rebutted these issues, telling the Journal that it is cooperating with the government. It said it is confident in the integrity of the trial and noted the overall study showed the superiority of ticagrelor over clopidogrel. There is no evidence the trial was unblinded and researchers used the same standards when qualifying all clinical events, including MIs, they noted. In addition, the company said it is not possible to compare event rates with clopidogrel in PLATO with other studies because the patient populations differ.

The Journal reports that Serebruany became embroiled in the controversy when asked by the FDA‘s Dr Thomas Marciniak to advise the agency about the PLATO data in 2010. Marciniak, who led the FDA’s review of PLATO, called AstraZeneca’s submission on serious adverse events the “worst submission” he ever encountered. According to the submission, he noted, 12 patients reported their own deaths by telephone. Before approving ticagrelor, the FDA requested an additional analysis of PLATO, and it was eventually approved in the US in July 2011. Ticagrelor was approved in Europe in December 2010 and is authorized for use in more than 100 countries.

The Journal called Serebruany an expert in the antiplatelet field but said he is a “controversial figure,” partly because of his financial ties to industry and repeated criticisms of new drug approvals. Through HeartDrug Research, Serebruany has worked on prasugrel (Effient, Lily/Daiichi-Sankyo), a competing antiplatelet agent, but has also done work for AstraZeneca.

REFERENCE

Burton TM. Doctor challenges testing of AstraZeneca’s Brilinta. Wall Street Journal, February 2, 2014. Available here.

SOURCE

http://www.medscape.com/viewarticle/820236?nlid=47583_1984&src=wnl_edit_medn_card&uac=93761AJ&spon=2

UPDATED 3/28/2013

How AstraZeneca Will Use A Diagnostic To Market Its Blood Thinner

by Matthew Harper, Forbes Staff on 3/21/2013

Earlier today I wrote about how AstraZeneca is telling investors that its blood-thinner Brilinta, used to prevent second heart attacks, could be a multi-billion dollar drug, at least twice as big as Wall Street analysts expect. So far the drug has been a disappointment.

I wrote:

Another key data point Astra presented was that blood levels of troponin, a muscle protein released by the heart during a heart attack, predict which patients get the most benefit from Brilinta. This data is not in AstraZeneca’s label, but a spokeswoman said that she believed it would be something the company can market to doctors.

via Can Pascal Soriot Turn Around AstraZeneca? It May Come Down To One Drug – Forbes.

But will the Food and Drug Administration allow Astra to tell doctors that? Stratification using troponin is not in Brilinta’s FDA-approved label, and off-label promotion is illegal. But Ferguson says that communications about troponin will be allowed because all patients with high troponin are patients who would be included in the FDA-approved indication. He confirms that use of troponin testing will be part of the new marketing plan for Brilinta.

SOURCE:

http://www.forbes.com/sites/matthewherper/2013/03/21/how-astrazeneca-will-use-a-diagnostic-to-market-its-blood-thinner/

Can Pascal Soriot Turn Around AstraZeneca? It May Come Down To One Drug

by Matthew Herper, Forbes Staff on 3/21/2013

This morning in New York, new AstraZeneca chief executive Pascal Soriot is telling investors how he is going to turn around the company that has had the absolute worst track record in research and development among any big pharmaceutical firm. The plan is fairly wide-ranging and involves a lot of the steps one might expect:

new layoffs (2,300 jobs);
a re-focusing of research and development on three areas: heart disease and diabetes; oncology; and respiratory and inflammation;
new R&D initiatives involving Moderna, a biotech company, and the Karolinska Instutet;
moving the company’s headquarters to its R&D hub in Cambridge, U.K.;
re-focusing on emerging markets, where AZ already gets $6 billion in sales, especially China.

But the short-term key to delivering on his promises today seems to come down to a single drug: Brilinta, the Plavix competitor thatAstraZeneca introduced in 2011 which has so far disappointed, generating just ~~$324~~ $89 million in global sales last year. This is a medicine to prevent heart attacks and strokes in patients who suffer acute coronary syndrome, the condition that occurs after a heart attack or serious heart-related chest pain. It works by preventing the formation of blood clots.

Plavix was the second biggest drug in the world, with $6 billion in annual sales, but it is now generic. The conventional wisdom is that it will be difficult to compete with cheap generics. Brilinta is actually trailing Effient, a similar medicine from Eli Lilly, in usage. Wall Street consensus currently sees Brilinta growing to become a moderate-sized drug in 2018, with $1.3 billion in annual sales. But AstraZeneca is saying that it thinks Brilinta can be a multi-billion dollar product. Astra has confirmed that this means Brilinta will have to surpass Effient. The newer drugs also cause more bleeding than Plavix.

What is the company’s argument? In his presentation today, Paul Hudson, Astra’s Executive Vice President, North America, said that the key would be focusing on one key fact: Brilinta reduced cardiovascular deaths by 21% compared to Plavix in a big clinical trial. That would mean that if everyone eligible for Brilinta got it, 100,000 lives would be saved.

But the reality is that doctors have been skeptical of that data because in the part of that trial that was run in North America, the benefit was less clear. AstraZeneca says that this may have been due to an interaction of Brilinta and aspirin and that, according to current cardiovascular guidelines, doctors should be prescribing less aspirin anyway.

Another key data point Astra presented was that blood levels of troponin, a muscle protein released by the heart during a heart attack, predict which patients get the most benefit from Brilinta. This data is not in AstraZeneca’s label, but a spokeswoman said that she believed it would be something the company can market to doctors.

A lot of what Astra will do in the short term on Brilinta will be blocking and tackling. It needs to pay bigger rebates to insurers to make sure that patients can get cheap access to the drug. (This is how discounts happen in the American insurance system: the patient pays a co-payment and the insurer pays full price for the drug, but then the drug maker gives the insurer money back to make the end cost cheaper.) It will also be doing a lot of medical marketing, involving its internal experts or paid, external doctors, to get the word out about the benefits of Brilinta.

Brilinta has other advantages (it stops acting quickly) and disadvantages (it must be given twice a day). But the other big question for expanding results is whether large clinical trials that are now ongoing will show that it works in a broader array of heart patients. Astra is starting a big trial to show Brilinta prevents strokes. These trials are risky and expensive, but there will be a big payoff if they work.

Astra has some other commercial levers to point to. It’s diabetes pill Onglyza, which is sold with Bristol-Myers Squibb, will have results in a big study of its efficacy in preventing heart disease before a similar study of Merck’s top-selling Januvia, which started first. Soriot has smart ideas about which drugs to advance into later testing. But Brilinta is going to be the biggest single indicator of whether Soriot’s new strategies are paying off.

SOURCE:

http://www.forbes.com/sites/matthewherper/2013/03/21/can-pascal-soriot-turn-around-astrazeneca-it-may-come-down-to-one-drug/

BRILINTA is an antiplatelet medication

Taking BRILINTA is a first step in the treatment your physician has chosen for you. At BRILINTA.com, you will find helpful information and useful learning tools to help you complete your course of BRILINTA therapy. Make sure you and your loved ones read through all of the sections.

What is BRILINTA?

BRILINTA is a type of prescription antiplatelet medication for people who have had a recent heart attack or severe chest pain that happened because their heart wasn’t getting enough oxygen and who are being treated with medicines or procedures to open blocked arteries in the heart. BRILINTA is used with aspirin to stop platelets from sticking together and forming a blood clot that could block blood flow to the heart and cause another, possibly fatal, heart attack. Platelets are small cells in the blood that help with normal blood clotting.

Take BRILINTA and aspirin exactly as instructed by your doctor: BRILINTA twice a day, plus one 81-mg aspirin tablet once a day. You should not take a dose of aspirin higher than 100 mg each day because it can affect how well BRILINTA works. Tell your doctor about any medicines you are taking that contain aspirin. Do not take any new medicines that contain aspirin.

Why BRILINTA?

BRILINTA used with aspirin lowers your chance of having another serious problem with your heart or blood vessels such as heart attack, stroke, or blood clots in your stent if you received one. These can be fatal. In fact, in a large clinical study BRILINTA was even better than Plavix^® (clopidogrel bisulfate) tablets at lowering your chances of having another heart attack.

BRILINTA is used to lower your chance of having another heart attack or dying from a heart attack, but BRILINTA (and similar drugs) can cause bleeding that can be serious and sometimes lead to death.

Taking BRILINTA

Complete the
Course Program

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA

BRILINTA is used to lower your chance of having another heart attack or dying from a heart attack or stroke, but BRILINTA (and similar drugs) can cause bleeding that can be serious and sometimes lead to death. Instances of serious bleeding, such as internal bleeding, may require blood transfusions or surgery. While you take BRILINTA, you may bruise and bleed more easily and be more likely to have nosebleeds. Bleeding will also take longer than usual to stop.

Call your doctor right away if you have any signs or symptoms of bleeding while taking BRILINTA, including: severe, uncontrollable bleeding; pink, red, or brown urine; vomit that is bloody or looks like coffee grounds; red or black stool; or if you cough up blood or blood clots.

Do not stop taking BRILINTA without talking to the doctor who prescribes it for you. People who are treated with a stent, and stop taking BRILINTA too soon, have a higher risk of getting a blood clot in the stent, having a heart attack, or dying. If you stop BRILINTA because of bleeding, or for other reasons, your risk of a heart attack or stroke may increase. Tell all your doctors and dentists that you are taking BRILINTA. To decrease your risk of bleeding, your doctor may instruct you to stop taking BRILINTA 5 days before you have elective surgery. Your doctor should tell you when to start taking BRILINTA again, as soon as possible after surgery.

Take BRILINTA and aspirin exactly as instructed by your doctor. You should not take a dose of aspirin higher than 100 mg daily because it can affect how well BRILINTA works. Tell your doctor if you take other medicines that contain aspirin. Do not take new medicines that contain aspirin.

Do not take BRILINTA if you are bleeding now, especially from your stomach or intestine (ulcer), have a history of bleeding in the brain, or have severe liver problems.

BRILINTA can cause serious side effects, including bleeding and shortness of breath. Call your doctor if you have new or unexpected shortness of breath or any side effect that bothers you or that does not go away. Your doctor can decide what treatment is needed.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. BRILINTA may affect the way other medicines work, and other medicines may affect how BRILINTA works.

Approved uses
BRILINTA is a prescription medicine for people who have had a recent heart attack or severe chest pain that happened because their heart wasn’t getting enough oxygen and who are being treated with medicines or procedures to open blocked arteries in the heart.

BRILINTA is used with aspirin to lower your chance of having another serious problem with your heart or blood vessels such as heart attack, stroke, or blood clots in your stent if you received one. These can be fatal.

Please read Prescribing Information, including Boxed WARNINGS.

Please read Medication Guide.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you are without prescription coverage and cannot afford your medication, AstraZeneca may be able to help. For more information, please visit www.AstraZeneca.com.

This product information is intended for US consumers only.

BRILINTA is a trademark of the AstraZeneca group of companies.

Plavix® is a registered trademark of sanofi-aventis.

SOURCE:

http://www.brilinta.com/antiplatelet-prescription-medication.aspx#au

http://www1.astrazeneca-us.com/pi/brilinta.pdf

BRILINTA (ticagrelor)

Ticagrelor (trade name Brilinta in the US, Brilique and Possia in the EU) is a platelet aggregation inhibitor produced by AstraZeneca. The drug was approved for use in the European Union by the European Commission on December 3, 2010.^[1]^[2] The drug was approved by the US Food and Drug Administrationon July 20, 2011.^[3]

Indications

Ticagrelor is indicated for the prevention of thrombotic events (for example stroke or heart attack) in patients with acute coronary syndrome or myocardial infarction with ST elevation. The drug is combined with acetylsalicylic acid unless the latter is contraindicated.^[4] Treatment of acute coronary syndrome with ticagrelor as compared with clopidogrel significantly reduces the rate of death.^[5]

Contraindications

Contraindications for ticagrelor are: active pathological bleeding and a history of intracranial bleeding, as well as reduced liver function and combination with drugs that strongly influence activity of the liver enzymeCYP3A4, because the drug is metabolized via CYP3A4 and excreted via the liver.^[4]

Adverse effects

The most common side effects are shortness of breath (dyspnea, 14%)^[6] and various types of bleeding, such as hematoma, nosebleed, gastrointestinal, subcutaneous or dermal bleeding. Allergic skin reactions such as rash and itching have been observed in less than 1% of patients.^[4]

Physical and chemical properties

Ticagrelor is a nucleoside analogue: the cyclopentane ring is similar to the sugar ribose, and the nitrogen rich aromatic ring system resembles the nucleobase purine, giving the molecule an overall similarity toadenosine. The substance has low solubility and low permeability under the Biopharmaceutics Classification System.^[1]

Ticagrelor as a nucleoside analogue

The nucleoside adenosinefor comparison

Pharmacokinetics

Ticagrelor is absorbed quickly from the gut, the bioavailability being 36%, and reaches its peak concentration after about 1.5 hours. The main metabolite, AR-C124910XX, is formed quickly via CYP3A4 by de-hydroxyethylation at position 5 of the cyclopentane ring.^[7] It peaks after about 2.5 hours. Both ticagrelor and AR-C124910XX are bound to plasma proteins (>99.7%), and both are pharmacologically active. Blood plasma concentrations are linearly dependent on the dose up to 1260 mg (the sevenfold daily dose). The metabolite reaches 30–40% of ticagrelor’s plasma concentrations. Drug and metabolite are mainly excreted via bile and feces.

Plasma concentrations of ticagrelor are slightly increased (12–23%) in elderly patients, women, patients of Asian ethnicity, and patients with mild hepatic impairment. They are decreased in patients that described themselves as ‘coloured’ and such with severe renal impairment. These differences are considered clinically irrelevant. In Japanese people, concentrations are 40% higher than in Caucasians, or 20% after body weight correction. The drug has not been tested in patients with severe hepatic impairment.^[4]

Mechanism of action

Like the thienopyridines prasugrel, clopidogrel and ticlopidine, ticagrelor blocks adenosine diphosphate (ADP) receptors of subtype P2Y₁₂. In contrast to the other antiplatelet drugs, ticagrelor has a binding site different from ADP, making it an allosteric antagonist, and the blockage is reversible.^[8] Moreover, the drug does not need hepatic activation, which might work better for patients with genetic variants regarding the enzyme CYP2C19 (although it is not certain whether clopidogrel is significantly influenced by such variants).^[9]^[10]^[11]

Comparison with clopidogrel

The PLATO trial, funded by AstraZeneca, in mid-2009 found that ticagrelor had better mortality rates than clopidogrel (9.8% vs. 11.7%, p<0.001) in treating patients with acute coronary syndrome. Patients given ticagrelor were less likely to die from vascular causes, heart attack, or stroke but had greater chances of non-lethal bleeding (16.1% vs. 14.6%, p=0.0084), higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding. Rates of major bleeding were not different. Discontinuation of the study drug due to adverse events occurred more frequently with ticagrelor than with clopidogrel (in 7.4% of patients vs. 6.0%, P<0.001)^[5] The PLATO trial showed a statistically insignificant trend toward worse outcomes with ticagrelor versus clopidogrel among US patients in the study – who comprised 1800 of the total 18,624 patients. The HR actually reversed for the composite end point cardiovascular (death, MI, or stroke): 12.6% for patients given ticagrelor and 10.1% for patients given clopidogrel (HR = 1.27). Some believe the results could be due to differences in aspirin maintenance doses, which are higher in the United States.^[12] Others state that the central adjudicating committees found an extra 45 MIs in the clopidogrel (comparator) arm but none in the ticagrelor arm, which improved the MI outcomes with ticagrelor. Without this adjudication the trials’ primary efficacy outcomes should not be significant^[13]

Consistently with its reversible mode of action, ticagrelor is known to act faster and shorter than clopidogrel.^[14] This means it has to be taken twice instead of once a day which is a disadvantage in respect of compliance, but its effects are more quickly reversible which can be useful before surgery or if side effects occur.^[4]^[15]

Interactions

Inhibitors of the liver enzyme CYP3A4, such as ketoconazole and possibly grapefruit juice, increase blood plasma levels and consequently can lead to bleeding and other adverse effects. Conversely, drugs that are metabolized by CYP3A4, for example simvastatin, show increased plasma levels and more side effects if combined with ticagrelor. CYP3A4 inductors, for example rifampicin and possibly St. John’s wort, can reduce the effectiveness of ticagrelor. There is no evidence for interactions via CYP2C9.

The drug also inhibits P-glycoprotein (P-gp), leading to increased plasma levels of digoxin, ciclosporin and other P-gp substrates. Ticagrelor and AR-C124910XX levels are not significantly influenced by P-gp inhibitors.^[4]

In the US a boxed warning states that use of ticagrelor with aspirin doses exceeding 100 mg/day decreases the effectiveness of the medication.^[16]

References

^ ^a ^b “Assessment Report for Brilique”. European Medicines Agency. January 2011.
^ European Public Assessment Report Possia
^ “FDA approves blood-thinning drug Brilinta to treat acute coronary syndromes”. FDA. 20 July 2011.
^ ^a ^b ^c ^d ^e ^f Haberfeld, H, ed. (2010) (in German). Austria-Codex (2010/2011 ed.). Vienna: Österreichischer Apothekerverlag.
^ ^a ^b Wallentin, Lars; Becker, RC; Budaj, A; Cannon, CP; Emanuelsson, H; Held, C; Horrow, J; Husted, S et al. (August 30, 2009). “Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes”. NEJM 361 (11): 1045–57. doi:10.1056/NEJMoa0904327. PMID 19717846.
^ Brilinta: Highlights of prescribing information
^ Teng, R; Oliver, S; Hayes, MA; Butler, K (2010). “Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects”. Drug metabolism and disposition: the biological fate of chemicals 38 (9): 1514–21. doi:10.1124/dmd.110.032250. PMID 20551239.
^ Birkeland, Kade; Parra, David; Rosenstein, Robert (2010). “Antiplatelet therapy in acute coronary syndromes: focus on ticagrelor”. Journal of Blood Medicine 1: 197–219.
^ H. Spreitzer (February 4, 2008). “Neue Wirkstoffe – AZD6140” (in German). Österreichische Apothekerzeitung (3/2008): 135.
^ Owen, RT, Serradell, N, Bolos, J (2007). “AZD6140”. Drugs of the Future 32 (10): 845–853. doi:10.1358/dof.2007.032.10.1133832.
^ Tantry, Udaya S; Bliden, Kevin P (2010). “First Analysis of the Relation Between CYP2C19 Genotype and Pharmacodynamics in Patients Treated With Ticagrelor Versus Clopidogrel”. Circulation: Cardiovascular Genetics 3: 556–566. doi:10.1161/CIRCGENETICS.110.958561.
^ Bernardo Lombo, José G Díez. Ticagrelor: the evidence for its clinical potential as an oral antiplatelet treatment for the reduction of major adverse cardiac events in patients with acute coronary syndromes Core Evid. 2011; 6: 31–42. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065559/
^ Serebruany VL, Atar D. Viewpoint: Central adjudication of myocardial infarction in outcome-driven clinical trials—Common patterns in TRITON, RECORD, and PLATO? Thromb Haemost 2012; DOI: 10.1160/TH12-04-0251. http://www.theheart.org/article/1433145/print.do
^ Miller, R (24 February 2010). “Is there too much excitement for ticagrelor?”. TheHeart.org.
^ H. Spreitzer (17 January 2011). “Neue Wirkstoffe – Elinogrel” (in German). Österreichische Apothekerzeitung (2/2011): 10.
^ July 20, 2011 AstraZeneca: Ticagrelor (Brilinta) Gains FDA Approval Larry Husten cardiobrief.org/2011/07/20/astrazeneca-ticagrelor-brilinta-gains-fda-approval/

SOURCE:

http://en.wikipedia.org/wiki/Ticagrelor

Read Full Post »

Sequencing the exomes of 1,100 patients with neurodegenerative and neuromuscular diseases: A consortium of 18 European and Australian institutions

Posted in Alzheimer's Disease, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Bone Disease and Musculoskeletal Disease, Cell Biology, Signaling & Cell Circuits, Cerebrovascular and Neurodegenerative Diseases, Chemical Genetics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, Genomic Testing: Methodology for Diagnosis, Innovations in Neurophysiology & Neuropsychology, Medical and Population Genetics, Molecular Genetics & Pharmaceutical, tagged Agilent Technologies, Decode Genetics, European Union, Motor neurone disease, Neurology, Neuromuscular disease, University of Tübingen on December 3, 2012| 1 Comment »

Reporter: Aviva Lev-Ari, PhD, RN

With $15.5M Grant, EU Consortium to Sequence 1,100 Exomes to Develop Diagnostics for Neurologic Diseases

November 28, 2012

By Molika Ashford

A consortium of 18 European and Australian institutions and industry partners will spend five years sequencing the exomes of 1,100 patients with neurodegenerative and neuromuscular diseases to create diagnostic panels and uncover novel therapeutic targets.

The group, known as the Neuromics Consortium, is funded with €12 million ($15.5 million) under the European Union’s seventh framework program.

Headed by the University of Tübingen, the project will involve collaboration between 12 academic centers. Iceland’s Decode Genetics will do the sequencing and will support analysis and return of results to participants. The group also plans to work with Agilent Technologies to develop and validate targeted sequencing-based diagnostic panels for specific neurologic diseases, including ataxia/paraplegias, spinal muscular atrophies and lower motor neuron diseases, and neuromuscular diseases, according to Tübingen’s Holm Graessner, the manager of the consortium.

Graessner told Clinical Sequencing News in an email that the Neuromics Consortium hopes its work will yield better diagnostic panels that can increase the diagnosis rate for ten main neurodegenerative and neuromuscular disease types — including ataxia, spastic paraplegia, Huntington’s disease, muscular dystrophy and spinal muscular atrophy — as well as provide information on genes and pathways that could inform new treatments.

According to the consortium, 30 percent to 80 percent of patients with these diseases are still undiagnosed by current single-gene tests or gene panels, and cohorts for each individual disorder are small. By combining patient groups and data from many centers and looking for commonality between some of these diseases, the consortium hopes to create diagnostics that cover a greater range of causative mutations.

While each specific disorder the group will study is relatively rare, many have overlapping manifestations, which suggest similarities in disease pathways pointing to common therapeutic strategies, according to the group.

Graessner said that the project’s whole-exome sequencing component will take place mostly in the first two years. According to the consortium’s plan, Decode Genetics — which expanded last year from array-based SNP genotyping research to a next-gen sequencing approach (CSN 11/9/2011) — will use its Illumina HiSeqs to sequence at least 1,100 subjects. The group expects this to increase the percentage of disease genes known for some of the more heterogeneous diseases in the set from about 50 percent to 80 percent.

According to Graessner, RNA sequencing is also part of the plan, as well as proteomic and other ‘omic analyses, especially as the researchers move from sequencing toward diagnostic panel development and therapeutic target research.

“We plan to [do whole-exome sequencing for] 1,100 subjects for gene identification … equally distributed over 10 disease areas,” Graessner wrote. “[This] will be done mainly in the first two years. However, for some of the diseases, such as ataxia/paraplegias, we have diagnostic panels already and in that case we [will] do the panels first and send the still unclear families for WES or WGS,” he wrote.

Graessner said that the group is just now shipping its first sample package to Decode. When this is finished the group will hold a workshop to discuss and train all the participating academic centers in the use of the Decode database for analysis of the results.

He said the team plans to work with the Halo Genomics division of Agilent, to validate diagnostic panels for ataxia, spinal muscular atrophies, lower motor neuron disease, and neuromuscular diseases. Halo was acquired by Agilent last year, and had developed an enrichment technology dubbed HaloPlex that it said was especially suited for targeted gene panels less than one megabase in size (IS 12/6/2011).

The group’s bioinformatics partner, Ariadne Genomics, will also analyze data to support the diagnostics research, as well as research on potential novel therapeutic targets, according to Graessner.

In a document describing the project, the consortium wrote that at the end of the funding period, it expects “to have elucidated the genetic basis for [more than] 80 [percent] of investigated patient groups.”

According to the group, the new genes will be added to existing databases and used to develop the first overlapping gene panel that can be used to diagnose several of these individual diseases, “overcoming time consuming and costly single gene analysis.”

Molika Ashford is a GenomeWeb contributing editor and covers personalized medicine and molecular diagnostics. E-mail her here.

Know How We ALL, Knowingly or Unknowingly, Consume Antibiotics and How it Effects Our Health

Posted in Infectious Disease & New Antibiotic Targets, tagged Antibacterial, bacteria, Copenhagen, European Union, Salmonella, United States, University College Cork, University of Copenhagen on August 29, 2012| 3 Comments »

Curated and Reported by: Dr. Venkat S. Karra, Ph.D.

Know How We ALL Knowingly or Unknowingly Consume Antibiotics and How it Effects Our Health

Billions of microbial cells live in the guts of humans and other animals. Research on these vast bacterial populations, called microbiomes, is just getting started, but scientists already know that some microbial boarders play a crucial role in breaking down nutrients in our diet. Some have also suspected that low-dose antibiotics, given to farm animals to make them grow bigger, could work by altering the gut microbiome.

To test this hypothesis, a team led by microbiologist Martin Blaser of the New York University School of Medicine in New York City added antibiotics to the drinking water of mice that had just been weaned. The medicine—either penicillin, vancomycin, a combination of the two, or chlortetracycline—was given at doses comparable to those approved by the U.S. Food and Drug Administration as growth promoters in farm animals. After 7 weeks, the group of mice on antibiotics had significantly more fat than a control group drinking plain water, the team reports online today in Nature. “This confirms what farmers have shown for 60 years, that low-dose antibiotics cause their animals to grow bigger,” Blaser says.

Patient Access to Medical Devices — A Comparison of U.S. and European Review Processes

Posted in Aortic Valve: TAVR, TAVI vs Open Heart Surgery, Cardiac & Vascular Repair Tools Subsegment, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, Massachusetts Niche Suppliers and National Leaders, Medical Devices R&D and Inventions, Mitral Valve: Repair and Replacement, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Stents & Tools, Valves & Tools, tagged CE mark, European Union, FDA, Food and Drug Administration, Health Technology Assessment, Medical device, United States on August 9, 2012| 1 Comment »

Patient Access to Medical Devices — A Comparison of U.S. and European Review Processes

Reporter: Aviva Lev-Ari, PhD, RN

Saptarshi Basu, M.P.A., and John C. Hassenplug, M.Sc.

N Engl J Med 2012; 367:485-488 August 9, 2012

The U.S. process for approving innovative, high-risk medical devices has been criticized for taking longer than the European approval process.1 This contention is often used to support the argument that the Food and Drug Administration (FDA) should lower its standards for approving medical devices, since a slow approval process is delaying Americans’ access to innovative and lifesaving technology. But a review of the data, using appropriate end points, suggests instead that it takes the same amount of time or less for patients to gain access to innovative, high-risk medical devices in the United States as it does in the four largest European markets (Germany, France, Italy, and Britain)2 — largely because patient access is generally delayed until reimbursement decisions are made, which often takes substantially longer in Europe than in the United States.

To compare the United States and Europe fairly on this front, three criteria must be considered: the level of device innovation, equivalent start and end points, and patient access as defined by time to reimbursement. First, we focused on innovative, high-risk devices because in the United States such devices require the strongest evidence of clinical benefit and are the subject of most debates about the relative effectiveness of approval processes in different countries. Furthermore, previous studies have shown that lower-risk devices achieve market access in a similar amount of time in the United States and in Europe.

Second, an accurate comparison of time to market access requires measurement of the total time that elapses between application submission and market access. Previous studies have compared the chronologic dates of application submission and market access, but the date an application is submitted varies from country to country.

Third, patient access should be equated with the availability of reimbursement rather than with device approval, because broad patient access to a new device doesn’t occur until reimbursement by a national or third-party payer is available. Previous comparisons of the U.S. and European systems have used the approval date to measure process duration, but innovative, high-risk devices don’t reach a market where most patients can benefit from them immediately after gaining regulatory approval, though they may be accessible to patients who can afford to pay out of pocket. Rather, there is a second level of review through which public or private insurers decide whether and at what price they will pay for a device. Generally, public systems take longer than private insurers to make reimbursement decisions, and significantly more Europeans than Americans have public insurance. Two thirds of the U.S. population is covered by private health insurance, whereas only a fifth receives publicly funded reimbursement, primarily administered by the Centers for Medicare and Medicaid Services (CMS).

For both private and public systems in the United States, the pathway to patient access to a device starts with the submission of an application to the FDA. The FDA reviews innovative, high-risk devices for safety and effectiveness (clinical benefit) under the premarket approval (PMA) process, and information on the duration of reviews is publicly available. In fiscal year 2011, the FDA approved 40 applications for PMA. The average review time was 13.1 months, with 8.4 months attributed to FDA review time, and 4.7 months to the time the agency waits for the sponsor to address deficiencies in the application (“sponsor time”).3 CMS provides reimbursement for the majority of devices when they earn FDA approval. For a limited number of devices each year, however, CMS conducts a national coverage determination in response to external requests for validation or for devices that have limited or conflicting evidence of clinical benefit. This process averaged 8.6 months over the past 5 fiscal years.4 Although it is difficult to obtain data on how long private insurers take to make coverage decisions, anecdotal information from private insurers suggests that decisions are made within a few weeks to a few months after FDA approval, depending on the amount and quality of evidence of clinical benefit.

In Europe, by contrast, most of the 27 member countries of the European Union (EU) have publicly financed health care systems; such systems cover approximately four fifths of the populations of the four largest device markets. All EU countries require devices to first obtain a Conformité Européenne (CE) marking, which refers to a symbol shown on products that indicates market approval throughout the EU. The CE marking process is conducted by for-profit, third-party “notified bodies” that have been accredited by a member country to assess device safety and performance but do not evaluate effectiveness (which requires more clinical data). Although publicly available data are limited, anecdotal information from notified bodies suggests that the process takes 1 to 3 months, excluding sponsor time.

Most European patients do not have access to innovative, high-risk devices as soon as the devices receive a CE marking. Each country must first make a decision about reimbursement, a process that varies substantially among countries.5 Though a CE marking can be granted on the basis of fewer clinical data than are required for FDA approval, European standards for reimbursement are often similar to or higher than those that the FDA imposes for device approval. European countries may require additional data on the device’s safety and effectiveness, as well as on cost-effectiveness.

In France, a centralized body makes reimbursement decisions after assessing the safety and effectiveness of individual devices. Reimbursement decisions in Italy are devolved to the various regions, and Britain and Germany conduct broader assessments of device types or procedures, rather than of individual devices. Typically, innovative devices not covered under an existing diagnosis-related group (DRG) require review under the lengthier Health Technology Assessment process, which assesses safety, clinical benefit, and cost-effectiveness. Government-provided information on time to reimbursement varies by country. Estimated time frames are an average of 71.3 months in Germany, a range of 36.0 to 48.0 months in France, a range of 16.4 to 26.3 months in Italy, and an estimated 18 months in Britain.

Using this information, we determined that the time it takes to bring innovative, high-risk devices to patients in the United States is similar to or shorter than that in the top four European markets (seefigure Comparison of Time to Market in Premarket Approval and Reimbursement Processes.). The public (CMS) process in the United States takes approximately as long as those in Italy and Britain, approximately half as long as that in France, and less than a third as long as that in Germany. The difference in time to market access is even greater when it comes to private insurers (covering the majority of the U.S. population), which often make reimbursement decisions within a few months after FDA approval.

To further illustrate this point, we compared the time to approval for five innovative, high-risk medical devices available in France, Italy, and the United States (see table Comparison of Time to Market Access for Five Innovative Devices in France, Italy, and the United States.). These case studies indicate that the average time to market access for these devices was 26.3 months in France, 30.8 months in Italy, and 15.3 months in the United States.

These numbers may not fully capture the reasons why a device reaches the market more quickly in one country than in another and do not reflect experiences with all innovative, high-risk devices. However, unless one uses equivalent standards in terms of the level of risk, the start and end points of the process, and the key end point of market access, accurate comparisons cannot be made.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on August 1, 2012, at NEJM.org.

SOURCE INFORMATION

From the Office of Planning, Office of the Commissioner, Food and Drug Administration, White Oak, MD.

Read Full Post »

BEYOND THE “MALE MODEL”: AN ALTERNATIVE FEMALE MODEL OF SCIENCE, TECHNOLOGY AND INNOVATION

Posted in International Global Work in Pharmaceutical, Pharmaceutical Industry Competitive Intelligence, Scientist: Career considerations, Statistical Methods for Research Evaluation, Technology Transfer: Biotech and Pharmaceutical, tagged Careers in Life Sciences, Doctor of Philosophy, European Union, National Science Foundation, research, Technology Transfer, Thomas Hunt Morgan on August 1, 2012| 3 Comments »

Reporter: Aviva Lev-Ari, PhD, RN

This post addresses related issues On the Career of the Life Sciences Scientist and compliments the following two posts on this Scientific Web Site:

August 1, 2012 — Introducing Career Streams into Academic Research

http://pharmaceuticalintelligence.com/2012/08/01/introducing-career-streams-into-academic-research/

June 27, 2012 — Picturing US-Trained PhDs’ Paths and Pharmaceutical Industry’s Crisis of Productivity: Partnerships between Industry and Academia

http://pharmaceuticalintelligence.com/2012/06/27/picturing-us-trained-phds-paths-pharmaceutical-industrys-crisis-of-productivity-partnerships-between-industry-and-academia/

BEYOND THE “MALE MODEL”: AN ALTERNATIVE FEMALE MODEL OF SCIENCE, TECHNOLOGY AND INNOVATION

THE TRIPLE HELIX ASSOCIATION NEWSLETTER, VOLUME 1 ISSUE 3 JULY 2012

Hélice www.triplehelixassociation.org Triple Helix X, 2012, Bandung, Indonesia . . . www.th2012.org

by Professor Henry Etzkowitz, President of the Triple Helix Association, Senior Researcher, H-STAR Institute, Stanford University, Visiting Professor, Birkbeck, London University and Edinburgh University Business School

henry.etzkowitz@stanford.edu

Professor Henry Etzkowitz paper is based on his Keynote Address to the FemTalent Conference, Barcelona, Spain 2011

I am often asked: why is a man studying women in science? The answer to that question is: my mother. She graduated with high honors in Geology from Hunter College, a public women’s college in New York City during the 1930’s depression. I had long thought that the reason why she didn’t pursue a career in geology was

because of the depression, that there were simply no jobs. However, on a research trip to the University of Texas at Austin, I visited the Engineering School which had a “wall of recognition” at the main entrance, including the names of many distinguished professors and practitioners, all of them men, who had graduated during the 1930’s depression and pursued careers in Geology. Perhaps the reason why a woman did not pursue a career in geological science at the time, might be found in the gender dynamics of science and technology. The broader question is how the best results may be attained from societal investment in human capital formation.

Firstly, we will consider the implications of findings from a study done in the 1990s, in the United States, sponsored by the National Science Foundation, of women’s experience in academic science (Etzkowitz, Kemelgor and Uzzi, 2000) including over 400 in-depth qualitative interviews conducted in a dozen leading research universities in five disciplines: biology, physics, chemistry and computer science:

1. One of the lessons from this study is that in Europe and other countries, there is a move to introduce the American system of higher education, including tenure procedures, which put a very strong emphasis on early achievement which, as we shall see, has deleterious consequences for women. Higher education policy makers in Europe and other parts of the world may want to look more closely at its effects before introducing this system, which is now taken as the gold standard in higher education. The introduction of the tenure system is driven by

international ranking procedures which drive movement from a system of relatively equal universities. Before abandoning values of equality, it should be seriously asked if introducing extreme inequalities will overall advance or inhibit quality academic research, teaching, and innovation.

2. Secondly, I discuss the Vanish Box model, derived from a four country study, sponsored by the European Union, DG Research, on Women and Technology Transfer (Ranga, et. al. 2008). During interviews with women in US academic science on Athena Unbound study, some of them would talk about colleagues who were no longer in the department, they were now in jobs elsewhere. I interviewed some of these women leaving academic science, and found that they were taking up careers in science-related professions such as science journalism, technology transfer, museology. etc. They were using their scientific training in translating science into use and spreading the results of science to a broader public. Rather than being “lost to science” as presumed by the “Leaky pipeline” thesis of science career loss; they were pursuing work-life balance in their new careers. This finding inspired the study sponsored by the European Union on Women and Technology Transfer.

3. Third, I outline a four phase model of women’s experience in science, technology, and innovation, “the Vanish Box”: after the magic trick of the “disappearance of re-appearance of a woman”. “The vanish box” model shows the dynamics of the historical experience of women in science, and questions the taken for granted “male model” of science that does not work for women or men who seek work-life balance.

4. Finally, we address the question of whether the Gender Revolution in science and technology is stalled or moving forward.

Gender Inequalities in Academic Careers

The historical relationship between status and gender provides a clue to understanding the underlying dynamics of women and men’s careers in science. Typically, there is strong participation of women in the early stages of development of a new discipline, but as the new area becomes prestigious and rewards increase, women disappear. As fields attain recognition and fruition, and the Nobel and other prizes are awarded, it is men who are there to receive them. There were a significant number of women working in “the fly room,” the drosophila genetics lab headed by Thomas Hunt Morgan at Colombia University, but as the field became prestigious, women virtually disappeared from classical genetics (Kohler, 1994).

Does this historical relationship between gender and science still hold today or has it changed? The most important finding from all the specific instances that we came across was that the most important thing holding back women’s advance in academic science was “inflexibility” of rules and procedures. It didn’t matter what the specific procedure was. For example, in the US it’s expected that that you should pursue your PhD at a different University than your undergraduate degree. This is the highest route to achievement. If a woman has a relationship, and the man moves will she leave the relationship to seek her competitive advantage?

On the other hand, if the man in the relationship moves, and the woman goes along, she may then have to move to a school that is not as good as the one which she otherwise might have gotten into with a broader range of selection. Thus, this informal rule of exogamy, mandating leaving the previous school or worksite at each point of progression, from undergraduate degree to PhD to entry level position, works against women’s advancement.

On the other hand, in Sweden the rule is the opposite. Instead of saying that you should move from one university to another, the rule is that you should stay at your own University; that if you are a highly successful junior scholar you will be kept within that University. A Swedish professor said, “why would I send my best

graduate student away? He is going to replace me when I retire.” So the rule in Sweden is endogamy that you stay within one university. Again, if a woman’s partner moves, and she moves with him, it will hurt her career, because she has left her university of origin. So which ever way the rule is, it is an inflexible rule, it has more negative consequences for women than for men. The gender policy implication is to increase flexibility in the system.

A female model of science, balancing work and family life, has been invented but it is a subsidiary and undervalued format that needs to be brought to the forefront and institutionalized. However, this would necessitate re-thinking aspects of the academic system, especially the US model, that unintentionally yet systematically works against women’s inclusion in the higher level of academic science. The US model of academic hierarchy, front loading in the academic career with a strong emphasis on youth and achievement

in the early years, is partly based on a mistaken idea that youth are more productive in science than people who are of an older age. That finding was documented in a study done by Merton and Zuckerman of “Aging and Age Structure” (1973). They found that “productivity was as high or even higher at the later stages of a scientific career”, and that makes sense. When you are more advanced in your career you have more access to resources, more

graduate students, more research associates, more people working with you. Co-authorship arises from having members of your research group being highly productive. Nevertheless, there is a strong belief that youth makes disproportionate scientific advances, and this has been the basis of a system in which there is a strong emphasis on early achievement during the first years of your career. There is a race to accumulate publications and research grants in order to be given a permanent position in a high status American University.

In Europe, the tradition has been once you are hired there is a probationary period and then you continue to be promoted or not. But in the United States there is a very sharp dividing line: an “up or out” system. The implications for women’s advancement in science, includes the contradiction between the “tenure clock”, typically of seven years, and the “biological clock”, the time when is possible to have children, and these coincide. Thus, women have to make the choice to postpone having children to after tenure, which then becomes their middle or late 30s. There were some women who didn’t want to postpone, and some of them rethought

their commitment to academic science and left for that reason. Occasionally, in some universities there has been some reform of these procedures to try to accommodate women by extending the clock. i.e. you can apply for a year extension to reduce your time in the workplace and/or take a break in order to have more time for one’s young children. Even this attempt to ameliorate the male model of science and make it more amenable to women’s

participation contains a contradiction: women are concerned that if they apply for this privilege that it will be held against them in the final review. The academic system requires a demonstration of full commitment to racing the clock, otherwise you will be viewed as insufficiently competitive. Moderating the conditions will be held against you, or at least that is the fear. The attempted reform has its dangers since many women feel that they may be given points off for taking advantage of the attempt to change the rules. The contradiction between the tenure clock and the biological clock encourages some women in academic science to seek an alternative career path.

An American professor talked about a leading female student who stayed in the same city and took a job at a local teaching college. But an exception was made for her because she was such an outstanding scholar that she was then brought back to the leading University in the same city where she had received her PhD and allowed to pursue a career at that university. The rule was counterproductive to the best use of talent, but this case was an

unusual exception. However, it is one that can be more regularly made if we are thinking of how to revise the system that works against women by following an implicit male model of science. Another negative factor is the “two out of three” time bind. In interviews in the US and Mexico, it was found that if you are trying to do three things, most women usually find it was too much, they could do advanced research in a highly productive way, and manage their family relationship, but that didn’t leave time for spending time in local politicking and talking with people, which is the way towards advancing within the academic system. So they could advance in their research career, but not in the career that would lead to becoming a chair person or administrator within academia. So this is the two out of three time bind.

Traditionally there has been a gendered division of labor where men worked with men and women with women, in gendered occupations. Some think that this occurred as a basis of naturally occurring gender divisions. But historically we can see that these gendered occupations change over time. I did my masters thesis on the male nurse, titled “the Precarious Identity of the Male Nurse” (Etzkowitz, 1971). The nursing profession in the

nineteenth century was entirely male, and began to change over to a female profession by the end of the nineteenth century, and by the middle of the twentieth century it was virtually entirely female. Thus, gendered professions can change over time and are subject to revision.

From “Leaky Pipeline” to the “Vanish Box”

The pipeline model has been based upon the movement from schooling into higher education and into careers; the premise that there should be an unimpeded flow. Over a period of twenty years, at maximum, women should be at the highest level of any occupation. Recruitment has taken place: young women now make up equal numbers in bachelor’s degrees, and the numbers are moving up in the PhDs. But they have not moved up at the same rate to the associate and full professor levels. The pipeline has not worked by filling it at one end, and expecting a changed result at the other. We need to make changes in the system to make the pipeline work. A gender neutral occupation would be one with flexibility in the role, and with balance between on-site and off-site work, and the possibility of equal participation of both genders in the occupation. What happens to women who, for one reason or another, don’t continue in an academic career in science? This was the question that we posed in: “Women in Science and Technology”(WIST) sponsored by the European Union. We identified that women who had left academic science, were reappearing in science related professions, using their scientific, networking and social skills in these new professions. In the UK, when opportunities opened up in the mid 1990s, female PhDs entered this career, following the States where women had risen to the top of their profession as heads of offices at major universities. From this study of women disappearing and reappearing from academia to science related professions, we developed a concept that we called the “vanish box” model (Etzkowitz and Ranga, 2011), that takes place in four stages:

1. The first is the disappearance of women: the disappearance that we found in the Athena Unbound study, the exclusionary practices, or the taken for granted male model of science which did not take account of women’s needs, of women’s life chances and lifestyles. They weren’t found at the highest levels of academic science to the extent that would be expected if the pipeline was working as it was supposed to, with women flowing in and being promoted up over a period of time. So disappearance.

2. The disappeared women are in the reserve army: at home or in part time positions unemployed or underemployed. The reserve army is called back when there is an emergency or a shortage. For example, during World War ll women PhD’s who had been unemployed or working as volunteers in their husband’s laboratory were called into full-time positions in the Manhattan Project and other Labs. After the War, some began to get academic positions and rose to the highest level after having been in the reserve army for many years.

3. The third phase of the model is the creation of new opportunities; either by emergency situations, or by the creation of new professions that require people with scientific training. An example of this was the Technology Transfer profession that we studied: a new profession that required people with scientific training and background and business training, and typically people with a scientific background would learn the business skills, take courses or even a master’s degrees in business. This provided opportunities, but there are still limitations: the new profession wasn’t as prestigious as the old one, and it had both advantages and disadvantages: working in a technology transfer office gives more of an opportunity for a work life balance, but the prestige of the profession isn’t that high and the opportunities for advancement are limited.

4. On the other hand, as the knowledge society advances, professions that translate knowledge into use become more prestigious and the profession also rises in status and prestige over time. That is what has been happening with technology transfer. The question that arises is, will it follow the same model of classical genetics, or will it lead to a new model of a gender neutral profession, with men and women working at the highest levels in a situation that allows for work-life balance? There is some evidence that this may be happening in small biotech firms. A recent study found that women recruited into these firms were taken seriously in their work, they were being promoted, and so the start-up biotechnology firm has offered evidence that there may be a changing relationship between gender and career advancement and new possibilities available in this area.

Beyond the “Male Model”: An Alternative Female Model

The American sociologist Cecilia Ridgeway has set forth the thesis of a stalled revolution, in the 1970’s large numbers of women entered professions in law and medicine but more recently advancement of women has halted. Pay differentials continue to exist. Women have not risen to positions in board of directors of firms to the same extent that might be expected. On the other hand, women now make up a majority of bachelor’s degrees recipients – over fifty percent in some places and as high as sixty percent in others. Forty years ago the percentage of women at MIT could be counted on the fingers of one hand. Today half of the undergraduate students at MIT are female. Once you get to the level of twenty percent social relations within organizations start to change; but they really transform at the fifty percent level. Typically in women’s entrepreneurship the service occupations make up the majority; but in Catalonia, there is a major change going on as the majority of the women in a program to support

entrepreneurship were in science and technology related occupations. The woman running this program said that the key issue is working with these entrepreneurs is how to grow their firms and still retain a work life balance. So the revolution is moving here. Academia is still resistant to change, but business has been moving faster, and Academia has to learn from industry. That is the next stage in making the gender revolution in science and technology.

To this end, the relationship between career structure and life cycle needs to be rethought (Etzkowitz and Stein, 1978). The current taken-for-granted career path is based on implicit male assumptions that do not take into account women’s greater responsibilities for family maintenance and societal reproduction that persist, even given good faith efforts on the part of men to play a greater role in child care (Kayyem, 2012). In the male model,

imposed on women as well, significant early achievement, typically involving a high time commitment, is the prerequisite for subsequent high-level positions. It is hypothesized that women’s difficulties in conforming to this model explains at least part of the variance in the paucity of women in high-level positions even as their participation rates increase.

An alternative female model, with a higher time commitment after child-rearing years, may be discerned. A Rockefeller University Professor, who started on her PhD at a later than usual age, and US Secretary of State Hilary Clinton, exemplify this alternative model that needs to be legitimized as an alternative path to high achievement. The current offering of a relaxed early career path in law firms is stigmatized as a “mommy track”

and reified into a permanent blockage to later high flying. When an alternative “female model” is available for women and men, gender democracy in science, technology and innovation, as well as in the larger society, will be a reality.

REFERENCES

Etzkowitz, H (1971), The Male Nurse: Sexual Separation of Labor in Society, Journal of Marriage and the Family.

Etzkowitz, H, and P. Stein. (1978) The Life Spiral: Human Needs and Adult Roles Journal of Economic and Family Issues. 1:4: 434-446

Etzkowitz, H, Kemelgor, C and Uzzi, B (2000), Athena Unbound: The Advancement of Women in Science and Technology Cambridge University Press.

Etzkowitz, H and Ranga, M (2011), Gender Dynamics in Science and Technology: From the “Leaky Pipeline” to the Vanish Box, Brussels Economic Review, 54:2/3.

Kayyem, J. (2012) The working moms debate International Herald Tribune June 27 Wednesday p.8.

Kohler, R. (1994) Lords of the Fly: Drosophila Genetics and the Experimental Life. Chicago: University of Chicago Press

Ranga, M et al (2008), Gender Patterns in Technology Transfer: Social innovation in the making?, Research Global, 4-5.

Ridgeway, C (2011), Framed by Gender: How Gender Inequality Persists in the Modern World, Oxford: Oxford University Press.

Zuckerman, H and Merton R (1972), Age, Ageing and Age Structure in Science. In Ageing and Society, Riley, M, Johnson, M and Foner, A, eds, Vol 3. New York: Russell Sage Foundation.

Read Full Post »

Biosimilars: Financials 2012 vs. 2008

Curator: Aviva Lev-Ari, PhD, RN

For IP and Legal aspects of Biosimilars, go to:

Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers

http://pharmaceuticalintelligence.com/2012/07/30/biosimilars-intellectual-property-creation-and-protection-by-pioneer-and-by-biosimilar-manufacturers/

For CMC and Regulatory Affairs of Biosimilars, go to:

Biosimilars: CMC Issues and Regulatory Requirements

http://pharmaceuticalintelligence.com/2012/07/29/biosimilars-cmc-issues-and-regulatory-requirements/

The patent provisions of the Biosimilar Act, 2009 establish demanding and time-sensitive disclosure requirements. ObamaCare upheld by the Supreme Court is a victory for future development of pathways for biosimilar regulatory approval and eventually biosimilar generic drugs.

With the upheld ObamaCare, critical parts of the PPACA constitutional, and with it the BPCIA giving the FDA authority to approve biosimilars.

Had the PPACA been stricken in part or in its entirety, it would have presented obstacles to the BPCIA surviving in its present form. The US government has been critical of the 12-year data exclusivity period for Pioneer Innovators, calling for it to be shortened to 7 years (12 years is favorable to Pioneer Innovators and less favorable for Biosimilar manufacturers). The upheld ObamaCare, PPACA and BPCIA, constitutional, has prevented a multiyear delay in biosimilar approval. Thus, it was the best scenario for the biologics industry.

Thus, projection of Sales for Biosmilars as % of top 100 U.S. Pharmaceutical will receive a special meaning and an expected enhanced market share for 2012 year end and beyond 2012.

Biosimilars are occupying the Following ranking in the U.S. Pharmacuetical Sales – 2012: Top 100 Drugs for Q1 2012 by Sales: 10, 11, 12 13, 15, 24, 27, 29, 33, 35, 39, 57, 58, 62, 65, 70, 72, 74, 90, 98, 99. In addition the following biosimilars did not make the Top 100 list:

Biosimilar Drugs by US Sales – not included in the Top 100 Drug List

Recombinate $2.9 1998 — Antihemophilic Factor VIII (Recombinant) by Baxter 5.7 Billion in 2012

Cerezyme $1.5 1994 — Gaucher disease and Fabrazyme for Fabry disease by Genzyme 200 millions in sales

TYSABRI(R) (natalizumab) revenues were $280 million, in-line with the second quarter of 2011 by Elan and Biogen

NovoSeven $1.4 1999 — Anti-fibrinolytics by Novo Nordisk – $1.5Billion

Synagis $1.3 1998 — Generic Name: palivizumab Anti-virals by AstraZeneca $570 millions

Humulin $1.1 1992 Insulin Human by Eli Lilly $ 1.2 Billion

Kogenate FS $1.1 1993 — octocog alfa Anti-fibrinolytics By Bayer $1.4 billion

U.S. Pharmacuetical Sales – 2012: Top 100 Drugs for Q1 2012 by Sales – Small Molecule Drugs (in green) and Biosimilars (in red)

The following is a list of the top 100 pharmaceutical drugs by retail sales in 2012, listed by U.S. sales value and drug name. Last updated: July 2012 (updated quarterly)

http://www.drugs.com/stats/top100/sales

Rank	Drug	Sales ($000)
1	PlavixBristol-Myers Squibb Company	1,620,790	Stats
2	NexiumAstraZeneca Pharmaceuticals	1,395,981	Stats
3	AbilifyOtsuka Pharmaceutical Co.	1,340,200	Stats
4	SingulairMerck & Co., Inc.	1,238,134	Stats
5	SeroquelAstraZeneca Pharmaceuticals	1,161,141	Stats
6	Advair DiskusGlaxoSmithKline	1,139,182	Stats
7	CrestorAstraZeneca Pharmaceuticals	1,117,904	Stats
8	CymbaltaEli Lilly and Company	1,029,262	Stats
9	atorvastatinGeneric Drug	952,407	Stats
10	HumiraAbbott Laboratories	928,124	Stats
11	RemicadeCentocor Ortho Biotech, Inc	899,453	Stats
12	EnbrelAmgen Inc.	890,135	Stats
13	NeulastaAmgen Inc.	849,971	Stats
14	LipitorPfizer Inc	840,715	Stats
15	RituxanGenentech, Inc	756,875	Stats
16	CopaxoneTeva Pharmaceuticals	748,585	Stats
17	AtriplaGilead Sciences, Inc.	694,901	Stats
18	OxyContin	662,876	Stats
19	SpirivaBoehringer Ingelheim Pharmaceuticals, Inc	659,818	Stats
20	AvastinGenentech, Inc	632,183	Stats
21	ActosTakeda Pharmaceuticals North America, Inc	630,970	Stats
22	JanuviaMerck & Co., Inc.	583,603	Stats
23	TruvadaGilead Sciences, Inc.	546,098	Stats
24	LantusSanofi-Aventis	520,584	Stats
25	DiovanNovartis Corporation	509,615	Stats
26	LexaproForest Pharmaceuticals, Inc	491,053	Stats
27	EpogenAmgen Inc.	489,570	Stats
28	LyricaPfizer Inc	458,171	Stats
29	Lantus SolostarSanofi-Aventis	448,388	Stats
30	enoxaparinGeneric Drug	442,263	Stats
31	EloxatinSanofi-Aventis	431,928	Stats
32	CelebrexPfizer Inc	430,993	Stats
33	HerceptinGenentech, Inc	425,687	Stats
34	Diovan HCTNovartis Corporation	415,475	Stats
35	LucentisGenentech, Inc	409,547	Stats
36	SynagisMedImmune, Inc	396,556	Stats
37	NamendaForest Pharmaceuticals, Inc	391,638	Stats
38	GleevecNovartis Corporation	391,072	Stats
39	AvonexBiogen Idec	388,623	Stats
40	VyvanseShire US Inc	387,167	Stats
41	olanzapineGeneric Drug	385,867	Stats
42	IncivekVertex Pharmaceuticals	371,349	Stats
43	One Touch Ultra	366,294	Stats
44	SuboxoneReckitt Benckiser Pharmaceuticals Inc.	338,840	Stats
45	methylphenidateGeneric Drug	337,211	Stats
46	ZetiaMerck & Co., Inc.	328,653	Stats
47	AndroGelAbbott Laboratories	311,850	Stats
48	ProvigilCephalon, Inc.	303,029	Stats
49	LidodermEndo Pharmaceuticals	301,354	Stats
50	TriCorAbbott Laboratories	298,834	Stats
51	SymbicortAstraZeneca Pharmaceuticals	290,669	Stats
52	CombiventBoehringer Ingelheim Pharmaceuticals, Inc	285,487	Stats
53	ProAir HFATeva Pharmaceuticals	284,647	Stats
54	Seroquel XRAstraZeneca Pharmaceuticals	282,416	Stats
55	amphetamine/dextroamphetamineGeneric Drug	275,447	Stats
56	NasonexMerck & Co., Inc.	274,748	Stats
57	NovologNovo Nordisk Inc.	266,305	Stats
58	ProcritJanssen Pharmaceuticals, Inc	264,190	Stats
59	AlimtaEli Lilly and Company	263,024	Stats
60	ViagraPfizer Inc	260,678	Stats
61	GeodonPfizer Inc	260,514	Stats
62	Rebif	258,088	Stats
63	budesonideGeneric Drug	257,243	Stats
64	NiaspanAbbott Laboratories	255,383	Stats
65	HumalogEli Lilly and Company	244,587	Stats
66	Flovent HFAGlaxoSmithKline	241,552	Stats
67	LovazaGlaxoSmithKline	239,845	Stats
68	LevemirNovo Nordisk Inc.	239,576	Stats
69	Adderall XRShire US Inc	239,097	Stats
70	NeupogenAmgen Inc.	238,427	Stats
71	ReyatazBristol-Myers Squibb Company	238,151	Stats
72	AranespAmgen Inc.	231,643	Stats
73	metoprololGeneric Drug	231,395	Stats
74	NovoLog FlexPenNovo Nordisk Inc.	227,228	Stats
75	VytorinMerck & Co., Inc.	218,215	Stats
76	JanumetMerck & Co., Inc.	212,596	Stats
77	IsentressMerck & Co., Inc.	211,526	Stats
78	escitalopramGeneric Drug	210,171	Stats
79	CialisEli Lilly and Company	206,996	Stats
80	AciphexEisai Corporation	203,097	Stats
81	PradaxaBoehringer Ingelheim Pharmaceuticals, Inc	201,065	Stats
82	SolodynMedicis Pharmaceutical Corporation	198,909	Stats
83	fentanylGeneric Drug	197,350	Stats
84	ZyprexaEli Lilly and Company	194,460	Stats
85	VelcadeTakeda Pharmaceuticals North America, Inc	188,583	Stats
86	RestasisAllergan, Inc	188,501	Stats
87	LunestaSunovion Pharmaceuticals Inc.	187,941	Stats
88	acetaminophen/hydrocodoneGeneric Drug	185,374	Stats
89	PrezistaJanssen Pharmaceuticals, Inc	182,859	Stats
90	PegasysGenentech, Inc	181,693	Stats
91	ZyvoxPfizer Inc	179,523	Stats
92	Prevnar 13Wyeth	179,085	Stats
93	LovenoxSanofi-Aventis	178,957	Stats
94	BenicarDaiichi Sankyo	174,619	Stats
95	VESIcareAstellas Pharma US	174,524	Stats
96	Ventolin HFAGlaxoSmithKline	172,707	Stats
97	OrenciaBristol-Myers Squibb Company	172,202	Stats
98	BetaseronBayer Healthcare Pharmaceuticals	172,143	Stats
99	ErbituxBristol-Myers Squibb Company	171,513	Stats
100	DexilantTakeda Pharmaceuticals North America, Inc	171,179	Stats

Source: IMS Health (Midas).

Biosimilars Drugs by US Sales – not included in the Top 100 Drug List

Recombinate $2.9 1998 — Antihemophilic Factor VIII (Recombinant) by Baxter 5.7 Billion in 2012

Cerezyme $1.5 1994 — Gaucher disease and Fabrazyme for Fabry disease by Genzyme 200 millions in sales

TYSABRI(R) (natalizumab) revenues were $280 million, in-line with the second quarter of 2011 by Elan and Biogen

NovoSeven $1.4 1999 — Anti-fibrinolytics by Novo Nordisk – $1.5Billion

Synagis $1.3 1998 — Generic Name: palivizumab Anti-virals by AstraZeneca $570 millions

Humulin $1.1 1992 Insulin Human by Eli Lilly $ 1.2 Billion

Kogenate FS $1.1 1993 — octocog alfa Anti-fibrinolytics By Bayer $1.4 billion

2011 US Sales vs. 2008 US Sales (in Billions) for Top Selling Biologics

Source for 2008 Sales

http://www.tbiweb.org/tbi/file_dir/TBI2009/Bao-lu%20Chen.pdf

Source for 20011, Q1 2012 Sales

http://www.drugs.com/stats/top100/sales

Drug Name, 2008 Sales, Year approved , Indication

[i.e. Drug Name Enbrel, 2008 Sales $8.0B, Year approved 1998 , Indication RA]

Enbrel $8.0 1998 — RA, psoriatic arthritis, or ankylosing spondylitis indication

Q1 2012	12 (1)	$890,135	1.92%	823	-4.63%
Q4 2011	11 (1)	$873,343	1.67%	863	1.77%
Q3 2011	12 (1)	$858,997	1.27%	848	-2.97%
Q2 2011	13 (2)	$848,230	3.77%	874	3.19%
Q1 2011	11	$817,401		847

http://www.drugs.com/stats/enbrel

Remicade $7.9 1998 — RA & Chron’s Disease

Q1 2012	11 (2)	$899,453	10.04%	1,556	10.04%
Q4 2011	13 (3)	$817,365	-7.02%	1,414	-9.82%
Q3 2011	10	$879,054	1.52%	1,568	1.03%
Q2 2011	10 (2)	$865,903	7.61%	1,552	7.11%
Q1 2011	12	$804,699		1,449

http://www.drugs.com/stats/remicade

Humira $7.3 2002 — treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis

Q1 2012	10	$928,124	2.50%	546	-2.85%
Q4 2011	10 (1)	$905,527	3.18%	562	2.55%
Q3 2011	11 (3)	$877,641	3.95%	548	3.01%
Q2 2011	14	$844,296	6.32%	532	2.31%
Q1 2011	14	$794,076		520

http://www.drugs.com/stats/humira

Rituxan $7.3 1997 — cancer medicines to treat non-Hodgkin’s lymphoma or chronic lymphocytic leukemia.

Q1 2012	15 (1)	$756,875	-1.91%	547	-0.91%
Q4 2011	14 (2)	$771,622	6.96%	552	4.74%
Q3 2011	16	$721,408	-1.77%	527	-1.86%
Q2 2011	16 (4)	$734,378	7.26%	537	5.09%
Q1 2011	20	$684,666

http://www.drugs.com/stats/rituxan

Second Quarter 2012 Highlights: RITUXAN(R) (rituximab) revenues from our unconsolidated joint business arrangement were $285 million for the quarter, an increase of 31% year-over-year. As previously disclosed, during the second quarter of 2011 our share of RITUXAN revenues from unconsolidated joint business was reduced by approximately $50 million to reflect our share of damages and interest that might be awarded in relation to an intermediate decision in Genentech, Inc.’s ongoing arbitration with Hoechst GmbH

http://www.marketwatch.com/story/correcting-and-replacing-biogen-idec-increases-revenue-18-to-14-billion-in-the-second-quarter-2012-07-24

Herceptin $5.7 1998 — treat metastatic breast cancer that has progressed after treatment with other chemotherapy

Q1 2012	33	$425,687	-0.06%	155
Q4 2011	33 (2)	$425,931	7.61%	155	4.73%
Q3 2011	31 (1)	$395,804	-0.64%	148	-0.67%
Q2 2011	32 (4)	$398,348	3.62%	149	1.36%
Q1 2011	36	$384,428		147

http://www.drugs.com/stats/herceptin

Lantus $5.1 2000 — long-acting form of the hormone insulin.

Q1 2012	29 (5)	$448,388	9.81%	3,737	7.32%
Q4 2011	34	$408,336	8.54%	3,482	7.07%
Q3 2011	34 (2)	$376,208	4.53%	3,252	6.00%
Q2 2011	36 (5)	$359,907	7.80%	3,068	8.30%
Q1 2011	41	$333,878		2,833

http://www.drugs.com/stats/lantus-solostar

Epogen/Procrit $5.1 1989 — Anemia, low RBC

Worldwide, sales of the two drugs – sold under the brand names Epogen, Procrit and Aranesp – exceeded $9 billion in 2005 for Amgen and Johnson & Johnson, their makers. Johnson & Johnson, which sells epoetin under the brand names Procrit in the United States and Eprex everywhere else, reported sales of $2.4 billion in the first nine months of 2006, down slightly from 2005.

Amgen Recalls Anemia Medications for Glass Fragments

09/24/2010 – Drug-makers Amgen (AMGN) and Johnson & Johnson (JNJ) are voluntarily recalling two brandsof an injectable anemia medication because vials containing the drug may have tiny glass flakes. The drug, Epoetin alfa, is marketed under the brand names Epogen and Procrit.Known as lamellae, the glass fragments are created by the interaction of the drug with glass vials during storage, Amgen said in a statement announcing the recall. The recall is being conducted in cooperation with the Food and Drug Administration, Amgen said.

http://www.dailyfinance.com/2010/09/24/amgen-recalls-epogen-procrit-glass-anemia-drugs/

http://healthfully.org/dnd/id9.html

Latest study shows anemia drugs Epogen, Aranesp and Procrit cause strokes, says FDA

Posted on January 7, 2010

Anemia drugs sold by Amgen and Johnson & Johnson have been reported to cause strokes when prescribed in high doses, according to an article from the FDA, recently published in the The New England Journal of Medicine. The law firm of Aylstock, Witkin, Kreis & Overholtz is investigating the FDA’s recent announcement.

The FDA commentary said the latest study and previous studies “raise major concerns” about the use of these drugs to treat anemia caused by kidney disease. The drugs are also used to treat anemia caused by chemotherapy. Studies over the past several years have revealed a link between the drugs and heart attacks, strokes, and other problems.

Amgen’s anemia drugs include Epogen and Aranesp. Johnson & Johnson sells anemia drug Procrit, which is produced by Amgen. The drugs are designed to raise red blood cell levels, to promote delivery of oxygen to body tissues.

http://www.awkolaw.com/news/heart-attacks/anemia-drugs-epogen-aranesp-procrit-cause-strokes-says-fda/

Epogen / Procrit / Aranesp: The July 2012 News Report Which Tells Story Of Big Pharma Profits Over Patient Safety And Drug Efficacy

Once The FDA Started Paying Attention The Writing On The Wall Became Apparent, Albeit Too Late For Some

(Posted by Tom Lamb at DrugInjuryWatch.com)

This lengthy and well-presented news report, “Anemia drugs made billions, but at what cost?”, written by Peter Whoriskey and published July 19, 2012 by The Washington Post (free registration required), is a must-read for anyone with a concern or interest in how larger pharmaceutical companies might put corporate profits ahead of patient safety and drug efficacy.

Here is an excerpt from this Washington Post article which will give you a sense of what went on that, in hindsight, is so disturbing:

For years, a trio of anemia drugs known as Epogen, Procrit and Aranesp ranked among the best-selling prescription drugs in the United States, generating more than $8 billion a year for two companies, Amgen and Johnson & Johnson. Even compared with other pharmaceutical successes, they were superstars. For several years, Epogen ranked as the single costliest medicine under Medicare: U.S. taxpayers put up as much as $3 billion a year for the drugs.

The trouble, as a growing body of research has shown, is that for about two decades, the benefits of the drug — including “life satisfaction and happiness” according to the FDA-approved label — were wildly overstated, and potentially lethal side effects, such as cancer and strokes, were overlooked.

Last year, Medicare researchers issued an 84-page study declaring that among most kidney patients, the original and largest market for the drugs, there was no solid evidence that they made people feel better, improved their survival or had any “clinical benefit” besides elevating a statistic for red blood cell count.

As for some of the key events which led up to this revelation of sorts, we start with a June 24, 2011 FDA press release, “FDA modifies dosing recommendations for Erythropoiesis-Stimulating Agents — Cites increased risk of cardiovascular events when used to treat chronic kidney disease”, which included the following:

The U.S. Food and Drug Administration today recommended more conservative dosing guidelines for Erythropoiesis-Stimulating Agents (ESAs) when used to treat anemia in patients with chronic kidney disease (CKD) because of the increased risks of cardiovascular events such as stroke, thrombosis, and death….

http://www.drug-injury.com/druginjurycom/2012/07/epogen-procrit-aranesp-stroke-thrombosis-death-side-effects-safety-risks-benefits-efficacy-fda.html

Procrit — (epoetin alfa) is a man-made form of a protein that helps your body produce red blood cells

Q1 2012	58 (3)	$264,190	-2.13%	295	-4.22%
Q4 2011	55 (2)	$269,937	3.58%	308	3.01%
Q3 2011	53 (12)	$260,610	-21.61%	299	-21.32%
Q2 2011	41 (7)	$332,466	7.04%	380	5.56%
Q1 2011	48	$310,606		360

http://www.drugs.com/stats/procrit

Epogen — (epoetin alfa) is a man-made form of a protein that helps your body produce red blood cells

Q1 2012	27 (7)	$489,570	-24.54%	555	-17.04%
Q4 2011	20 (2)	$648,794	4.67%	669	3.40%
Q3 2011	22 (2)	$619,828	-13.96%	647	-18.41%
Q2 2011	20 (1)	$720,376	3.32%	793	4.48%
Q1 2011	19	$697,224		759

http://www.drugs.com/stats/epogen

Neulasta $4.2 2002 — used to prevent neutropenia, a lack of certain white blood cells caused by receiving chemotherapy. stimulates the bone marrow and promotes the growth of white blood cells called neutrophils

Q1 2012	13 (1)	$849,971	3.33%	331	1.53%
Q4 2011	12 (2)	$822,578	4.59%	326	3.49%
Q3 2011	14 (1)	$786,464	-3.86%	315	-5.69%
Q2 2011	15	$818,068	4.04%	334	3.41%
Q1 2011	15	$786,288		323

http://www.drugs.com/stats/neulasta

Novolog $3.7 2000 — Insulin aspart is a fast-acting form of insulin. NovoLog is used to treat type 1 (insulin-dependent) diabetes in adults and children who are at least 2 years old. It is usually given together with a long-acting insulin.

Q1 2012	57 (6)	$266,305	5.67%	2,980	3.72%
Q4 2011	63 (3)	$252,015	0.97%	2,873	-0.48%
Q3 2011	60 (1)	$249,591	-0.96%	2,887	-2.66%
Q2 2011	61 (5)	$252,010	3.16%	2,966	-0.70%
Q1 2011	66	$244,297		2,987

http://www.drugs.com/stats/novolog

Erbitux $3.6 2004 — used to treat cancers of the colon and rectum. It is also used to treat head and neck cancer.

Q1 2012	99 (2)	$171,513	2.30%	266	3.91%
Q4 2011	97 (7)	$167,657	-0.15%	256	0.79%
Q3 2011	90 (3)	$167,909	-2.48%	254	-1.93%
Q2 2011	93 (2)	$172,185	-0.89%	259	-0.38%
Q1 2011	95	$173,735		260

http://www.drugs.com/stats/erbitux

Aranesp $3.2 2001 — Anemia, low RBC, (darbepoetin alfa) is a man-made form of a protein that helps your body produce red blood cells.

Q1 2012	72 (6)	$231,643	-5.86%	293	-7.86%
Q4 2011	66 (15)	$246,056	-6.07%	318	-3.64%
Q3 2011	51 (3)	$261,967	-10.25%	330	-11.29%
Q2 2011	48 (3)	$291,873	-1.03%	372	-1.33%
Q1 2011	51	$294,912		377

http://www.drugs.com/stats/aranesp

The article reports on the decline of worldwide sales of Aranesp drug from Thousand Oaks, California-based Amgen Inc. as of the second quarter of 2007. According to Amgen, the 10% decrease of Aranesp worldwide sales was due to the reimbursement issues related to the anemia drug and the drop of U.S. demand for drug, in which the U.S. Aranesp reported sales in the second quarter of 2007 was only $578 million from $713 million in 2006.

http://connection.ebscohost.com/c/articles/26375335/amgen-posts-lower-aranesp-sales

1/24/2011, Amgen boosts prices to offset Aranesp sales

Amgen is hiking prices to make up for the shrinking sales volume of its anemia drug Aranesp. Bloomberg reports that Amgen raised the price tag on Aranesp itself by 4.4 percent, but also marked up the white-blood-cell-boosting meds Neulasta and Neupogen by 2.9 percent.

http://www.fiercepharma.com/story/amgen-boosts-prices-offset-aranesp-sales/2011-01-24

Recombinate $2.9 1998 — Antihemophilic Factor VIII (Recombinant)

BioScience core franchises include: Hemophilia, Biotherapeutics, BioSurgery and Vaccines. BioScience products represent approximately 45 percent of Baxter’s annual sales, totaling $5.7 billion in 2010.

2007 Outlook – Sales within Baxter’s BioScience business totaled $1.2 billion, an increase of 18 percent from the same period last year. This growth was driven by record sales of ADVATE, Antihemophilic Factor (Recombinant), Plasma/Albumin Free Method (rAHF-PFM) for the treatment of hemophilia A, antibody therapy products, including GAMMAGARD LIQUID(TM) [Immune Globulin Intravenous (Human)] (IVIG) 10% Solution for the treatment of primary immunodeficiencies, specialty plasma therapeutics and biosurgery products. Medication Delivery sales increased 7 percent to $1.0 billion, with increased sales of infusion systems, intraveneous solutions and parenteral nutrition products, along with accelerated growth in the company’s drug delivery business. Renal sales increased 6 percent to $537 million reflecting accelerating gains in peritoneal dialysis patients globally.

http://www.drugs.com/news/baxter-s-fourth-quarter-financial-results-exceed-expectations-5128.html

Lucentis $2.7 2006 intraocular injection. (ranibizumab injection) is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A).

Date Range	Sales Rank	Sales ($000)		Units (000)
Q1 2012	35 (5)	$409,547	-6.89%	224	-5.88%
Q4 2011	30 (2)	$439,867	2.44%	238	2.59%
Q3 2011	28 (2)	$429,393	1.13%	232	0.87%
Q2 2011	30 (3)	$424,611	0.95%	230	1.32%
Q1 2011	33	$420,635		227

http://www.drugs.com/stats/lucentis

http://www.gene.com/gene/about/ir/historical/product-sales/lucentis.html

Lucentis brought in $1.7 billion for Roche last year, according to data compiled by Bloomberg.Alimera Sciences Inc. (ALIM), based in Alpharetta, Georgia, and Psivida Corp. (PSDV) also are developing a diabetic macular edema treatment known as Iluvien. The FDA has twice rejected Iluvien, most recently in November.

The FDA pooled results from two Roche clinical trials and found 39 percent of patients who used the 0.3 milligram dose were able to read three additional lines of letters on an eye chart after two years compared to 41 percent who had the same effect on the 0.5 milligram dose, according to an FDA staff report released July 24.

Genentech recommended approval of the 0.3 milligram dose in its application to the FDA since there isn’t evidence of additional benefit of the higher dose, Terence Hurley, a spokesman for the company, said in an e-mail.

Patients who received the monthly injection also were significantly more likely than those who received fake doses of the drug to achieve 20/40 vision, enough eyesight to drive.

http://www.bloomberg.com/news/2012-07-26/roche-s-lucentis-backed-by-fda-panel-for-diabetic-blindness-1-.html

Avonex $2.6 1996 — Multiple Sclerosis, a form of protein called beta interferon that occurs naturally in the body. Interferons help the body fight viral infections. Avonex is used to treat patients with relapsing forms of multiple sclerosis to slow the accumulation of physical disability. This medication will not cure MS, it will only decrease the frequency of relapse symptoms.

Q1 2012	39 (1)	$388,623	2.22%	130	-3.70%
Q4 2011	38 (5)	$380,189	0.19%	135	-2.17%
Q3 2011	33	$379,457	-0.05%	138	-1.43%
Q2 2011	33 (4)	$379,639	2.45%	140	-1.41%
Q1 2011	37	$370,570		142

http://www.drugs.com/stats/avonex

Second-quarter net income surged 34 percent to $386.8 million, or $1.61 a share, from $288 million, or $1.18, a year earlier, the Weston, Massachusetts-based company said today in a statement. Earnings excluding some items of $1.82 topped by 26 cents the average of 21 analysts’ estimates (BIIB) compiled by Bloomberg. Revenue beat estimates by about $90 million.

Biogen said profit this year is expected to be more than $6.20 a share, 5 cents higher than its May 1 forecast (BIIB). The company has been increasing sales of Avonex, Rituxan and Tysabri, another MS therapy, while developing new medicines to introduce to the market.

http://www.businessweek.com/news/2012-07-24/biogen-second-quarter-profit-rises-as-avonex-sales-increase

AVONEX(R) (interferon beta-1a) revenues increased 16% year-over-year to $762 million.

http://www.marketwatch.com/story/correcting-and-replacing-biogen-idec-increases-revenue-18-to-14-billion-in-the-second-quarter-2012-07-24

Novolin $2.5 1991 — Novolin R (insulin regular) is a short-acting form of human insulin, Diabetes, Type 1 Type 2

Date Range	Sales Rank	Sales ($000)		Units (000)
Q1 2012	74 (2)	$227,228	8.96%	2,489	13.81%
Q4 2011	76 (4)	$208,552	10.19%	2,187	6.73%
Q3 2011	80 (6)	$189,267	4.15%	2,049	4.92%
Q2 2011	86 (7)	$181,733	3.71%	1,953	29.60%
Q1 2011	93	$175,235		1,507

http://www.drugs.com/stats/novolog-flexpen

Novo Nordisk launches iPhone app Posted 17th September 2010, 15:11:54

An iPhone app has been launched by Novo Nordisk in the US which lets healthcare staff check dosage guidelines for diabetes patients.

Novo Dose provides product-specific data for the company’s insulin analog agents Levemir (insulin detemir), NovoLog (insulin aspart) and NovoLog Mix (insulin aspart protamine/insulin aspart injectable).

Combined sales of the three medications increased by 24% last year, feeding a double-digit growth in Novo Nordisk sales and profits.

Novo Dose, the second diabetes app created by the industry, tells professionals when and how to dose the drugs, how to titrate and provides information on the blood glucose goals of patients.

Commenting on the new technology, Anup Kumar Sabharwal, an endocrinologist at the University of Miami Clinics’ Diabetes Research Institute, said: “This is where modern medicine is headed.”

Humalog $2.2 1996 Humalog is used to treat type 1 (insulin-dependent) diabetes in adults. Insulin lispro is a fast-acting form of insulin. It is usually given together with another long-acting insulin. It works by lowering levels of glucose in the blood. Humalog is also used together with oral (taken by mouth) medications to treat type 2 (non insulin-dependent) diabetes in adults.

Q1 2012	65	$244,587	-2.70%	2,570	-3.85%
Q4 2011	65 (2)	$251,367	3.78%	2,673	2.81%
Q3 2011	63 (4)	$242,208	-0.75%	2,600	-1.78%
Q2 2011	67 (5)	$244,050	4.83%	2,647	1.15%
Q1 2011	72	$232,809		2,617

http://www.drugs.com/stats/humalog

Pegasys $2.0 2002 — (peginterferon alfa-2a) is made from human proteins that help the body fight viral infections. Pegasys is used to treat chronic hepatitis B or C. It is often used together with another medication called ribavirin (Copegus, Rebetol, RibaPak, Ribasphere, RibaTab).

Q1 2012	90 (1)	$181,693	3.92%	87	3.57%
Q4 2011	91 ()	$174,833		84

http://www.drugs.com/stats/pegasys

Rebif $1.7 2002 — (interferon beta-1a) is a protein identical to one found in the body. Interferon beta-1a is made from human proteins. Interferons help the body fight viral infections. Rebif is used to treat relapsing multiple sclerosis (MS). This medication will not cure MS, it will only decrease the frequency of relapse symptoms.

Q1 2012	62 (1)	$258,088	-0.21%	540	-9.09%
Q4 2011	61 (7)	$258,643	0.43%	594	-0.34%
Q3 2011	54 (5)	$257,535	1.48%	596	-1.49%
Q2 2011	59 (2)	$253,780	0.25%	605	-0.66%
Q1 2011	61	$253,143		609

http://www.drugs.com/stats/rebif

Cerezyme $1.5 1994 — Gaucher disease and Fabrazyme for Fabry disease.

Last year Genzyme was forced to temporarily close its manufacturing plant in Boston due to a viral contamination. The interruption lead to shortages of two key drugs: Cerezyme for Gaucher disease and Fabrazyme for Fabry disease.

That crisis sent the company’s stock price plummeting from nearly $84 in 2008 to a low earlier this year of $45.39. Sanofi’s offer to acquire the company for $18.5 billion, or $69 a share — along with a 14 percent rise in the NYSE Arca Biotech Index since late July — have helped the shares rebound.

But Genzyme is now on a mission to prove to shareholders that it is worth more than Sanofi is offering, and executives told investors on a conference call that the third quarter marks the beginning of its financial turnaround.

Third-quarter sales of Cerezyme, the company’s top drug, rose to $179.8 million from $93.6 million a year earlier, beating analysts’ average forecast of $175 million.

“In the third quarter we saw our financial recovery start to take effect, and we expect that this will accelerate during the fourth quarter as Cerezyme patients are able to return to normal dosing levels and we begin to increase shipments of Fabrazyme,” Genzyme CEO Henri Termeer said in a statement.

http://www.reuters.com/article/2010/10/20/us-genzyme-idUSTRE69J2S520101020

Cerezyme is the principal drug for Gaucher patients. In the first quarter of 2012 Genzyme (now part of Sanofi (SNY))reported Cerezyme sales of 149 million euros (approx. $194 million), up 5.8% from the same quarter of the previous year. The other supplier Shire (SHPGY) reported $72 million in Vpriv sales, up 22%. There is now a third supplier, Pfizer (PFE), teamed up with the Israeli company Protalix Biotherapeutics (PLX), whose product was approved by the FDA in May 2012. Elelyso (taliglucerase alfa) is now available in the US.

http://seekingalpha.com/article/694801-gaucher-disease-the-fight-for-market-share

Product	Cerezyme
	2009	2010	2011
Total	793	720	885
Ann. Growth Total		-9%	23%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=15461&componentID=1002

Tysabri $1.4 2004 — Multiple Sclerosis by Elan and Biogen

Global in-market sales of TYSABRI in the second quarter of 2012 were $395 million, an increase of 2% over the second quarter of 2011. The total was comprised of $211 million in U.S. sales and $184 million in sales outside the U.S.

http://www.marketwatch.com/story/correcting-and-replacing-biogen-idec-increases-revenue-18-to-14-billion-in-the-second-quarter-2012-07-24

TYSABRI(R) (natalizumab) revenues were $280 million, in-line with the second quarter of 2011.

http://www.marketwatch.com/story/correcting-and-replacing-biogen-idec-increases-revenue-18-to-14-billion-in-the-second-quarter-2012-07-24

ITALIAN DISPUTE

Elan derives its revenue almost exclusively from Tysabri and it reported total sales for the three months to June 30 of $288 million, up 6 percent on a year ago once sales from its since-divested drug delivery business are omitted.

That compared to the $299 million forecast by four analysts surveyed by Reuters and was driven by in-market sales of Tysabri that rose 2 percent year-on-year to $395 million, also shy of the $419 million expected by analysts.

Biogen, which detailed the sales numbers when it reported second quarter results on Tuesday, attributed the softer-than-expected Tysabri sales to a dispute with the Italian government over pricing.

The number of patients on Tysabri rose 4 percent to 69,100, maintaining Elan and Biogen’s 10 to 12 percent share of the MS drug market in the face of competition from Swiss drugmaker Novartis AG’s Gilenya treatment, the first multiple sclerosis pill to come on the market.

The average addition of 185 new patients per week was the highest quarterly run-rate since the fourth quarter of 2009.

http://in.reuters.com/article/2012/07/25/elan-idINL6E8IP1VV20120725

NovoSeven $1.4 1999 — Anti-fibrinolytics by Novo Nordisk —

Generic Name:

eptacog alfa

Product	NovoSeven
	2009	2010	2011
Total	1,324	1,431	1,559
Ann. Growth Total		8%	9%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&id=13483&lType=modData&componentID=1002

Synagis $1.3 1998 — Generic Name: palivizumab Anti-virals by AstraZeneca

Product	Synagis
	2009	2010	2011
Total	1,042	906	570
Ann. Growth Total		-13%	-37%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=91&componentID=1002

Neupogen $1.3 1991 — (filgrastim) is a man-made form of a protein that stimulates the growth of whiteblood cells in your body. White blood cells help your body fight against infection. Neupogen is used to treat neutropenia, a lack of certain white blood cells caused by cancer,bone marrow transplant, receiving chemotherapy, or by other conditions.

Q1 2012	70	$238,427	0.06%	170	-2.86%
Q4 2011	70 (5)	$238,289	0.16%	175	10.76%
Q3 2011	65 (5)	$237,915	0.69%	158	0.64%
Q2 2011	70 (4)	$236,294	2.51%	157	0.64%
Q1 2011	74	$230,515		156

http://www.drugs.com/stats/neupogen

Betaseron $1.2 1993 — (interferon) is made from human proteins. Interferons help the body fight viral infections. Betaseron is used to treat relapsing multiple sclerosis (MS). Betaseron will not cure MS, it will only decrease the frequency of relapse symptoms.

Q1 2012	98 (1)	$172,143	2.93%	67	-10.67%
Q4 2011	99 (12)	$167,236	-3.76%	75	-5.06%
Q3 2011	87 (2)	$173,769	-2.89%	79	-2.47%
Q2 2011	89 (4)	$178,938	-2.17%	81	-7.95%
Q1 2011	85	$182,908		88

http://www.drugs.com/stats/betaseron

Humulin $1.1 1992 Insulin Human by Eli Lilly

Product	Humulin R
	2009	2010	2011
Total	1,022	1,089	1,249
Ann. Growth Total		7%	15%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=12399&componentID=1002

Kogenate FS $1.1 1993 — octocog alfa Anti-fibrinolytics By Bayer

Product	Kogenate
	2009	2010	2011
Total	1,238	1,332	1,496
Ann. Growth Total		8%	12%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=11681&componentID=1002

Conclusion

Biosimilars are defined as biological products similar, but not identical, to the reference biological products that are submitted for separate marketing approval following patent expiration of the reference biological products. As one of the ICH members, the US needs to catch up with the EU and Japan as those two countries have already issued regulatory guidelines for biosimilars.

Once Congress establishes a legal framework, FDA is expected to set up a biosimilar approval pathway which will be similar to those in the EU and Japan and harmonized under ICH. The biosimilar will need a full CMC development package plus demonstration of comparable quality attributes and comparable efficacy and safety to the innovator’s product. Table 5 provides a comparison summary between small-molecule generics and biosimilars. It will take a much bigger effort to develop a biosimilar than a generic drug. Automatic substitution between the innovator product and a biosimilar is not appropriate as a biosimilar is not a generic version of the innovator product and is approved based on comparability to the innovator product.