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Spark Therapeutics’ $4.8Billion deal Confirmed as Biggest VC-backed Exit in Philadelphia

Posted in Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Institutional Capital Raised by Female Founders, Pharmaceutical Drug Discovery, Regenerative Biology and Medicine, Transformative Technologies in Healthcare, Venture Capital, tagged Ben Franklin Partners, Biotech Investment and Venture Growth: The Franchising of Intellectual Property as a Business Model, Children's Hospital of Philadelphia, gene therapy, Gene Therapy for Inherited Retinal Diseases, PennInovation, philadelphia, Roche, University of Pennsylvania on March 1, 2019| Leave a Comment »

From Technicall.y Philly.com

Reporter: Stephen J. Williams, PhD

Spark Therapeutics’ $4.8B deal confirmed as biggest-ever VC-backed exit in Philly

Quick update on this week’s news: The University City life sciences company’s acquisition by Swiss pharma giant Roche is the biggest acquisition ever of a VC-backed company within city limits, per PitchBook and PACT.

By Roberto Torres/ REPORTER

The eye-popping $4.8 billion sticker price on Spark Therapeutics’acquisition deal with Roche announced on Monday is shaping up to be the largest exit ever within city limits for a venture-backed company, according to data from financial data provider PitchBook and the Philadelphia Alliance for Capital and Technologies (PACT).

“Filtering down to just Philadelphia proper does reveal that Spark Therapeutics, once the deal closes, will be the biggest exit ever for Philly-based venture-backed exits,” the company said in an email, citing data from an upcoming report.

According to the Seattle-based company’s data, the current holder of the largest Philly-proper exit title goes to Avid Radiopharmaceuticals, which in 2010 announced its acquisition by Lilly in a deal valued at up to $800 million.

Founded in 2013, Spark is a publicly traded spinout of Children’s Hospital of Philadelphia (CHOP), which invested $33 million in the company. The Philadelphia Inquirer reports that CHOP stands to reap a total return of $430 million for its minority stake in Spark Therapeutics.

As part of the acquisition deal, the company will remain based out of 3711 Market St., and continue to do business as a standalone Roche company.

“This transaction demonstrates the enormous value that global biotech companies like Roche see in gene therapy, a field in which Philadelphia is the unquestioned leader,” said Saul Behar, senior VP of advancement and strategic initiatives at the University City Science Center, the West Philly research park where Spark began and grew its operations. “[This] further validates Greater Philadelphia’s status as a biotech hub with a very bright future.”

Spark CEO Jeff Marrazzo said the deep pool of resources from Roche, the company plans to “accelerate the development of more gene therapies for more patients for more diseases and further expedite our vision of a world where no life is limited by genetic disease.”

Roche is developing a high-throughput low cost sequencer for NGS

Posted in Bio Instrumentation in Experimental Life Sciences Research, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Clinical Diagnostics, Clinical Genomics, Next Generation Sequencing (NGS), tagged clinical genomics, deep sequencing, genomics, high throughput, highthroughput, next generation sequencing, NGS, Roche, Roche Diagnostics, Roche Institute of Molecular Biology on December 16, 2015| Leave a Comment »

Roche is developing a high-throughput low cost sequencer for NGS

Reporter: Stephen J. Williams, PhD

Reported from Diagnostic World News

Long-Read Sequencing in the Age of Genomic Medicine

By Aaron Krol

December 16, 2015 | This September, Pacific Biosciences announced the creation of the Sequel, a DNA sequencer half the cost and seven times as powerful as its previous RS II instrument. PacBio, with its unique long-read sequencing technology, had already secured a place in high-end research labs, producing finished, highly accurate genomes and helping to explore the genetic “dark matter” that other next-generation sequencing (NGS) instruments miss. Now, in partnership with Roche Diagnostics, PacBio is repositioning itself as a company that can serve hospitals as well.

“Pseudogenes, large structural variants, validation, repeat disorders, polymorphic regions of the genome―all those are categories where you practically need PacBio,” says Bobby Sebra, Director of Technology Development at the Icahn School of Medicine at Mount Sinai. “Those are gaps in the system right now for short-read NGS.”

Mount Sinai’s genetic testing lab owns three RS II sequencers, running almost around the clock, and was the first lab to announce it had bought a Sequel just weeks after the new instruments were launched. (It arrived earlier this month and has been successfully tested.) Sebra’s group uses these sequencers to read parts of the genome that, thanks to their structural complexity, can only be assembled from long, continuous DNA reads.

There are a surprising number of these blind spots in the human genome. “HLA is a huge one,” Sebra says, referring to a highly variable region of the genome involved in the immune system. “It impacts everything from immune response, to pharmacogenomics, to transplant medicine. It’s a pretty important and really hard-to-genotype locus.”

Nonetheless, few clinical organizations are studying PacBio or other long-read technologies. PacBio’s instruments, even the Sequel, come with a relatively high price tag, and research on their value in treating patients is still tentative. Mount Sinai’s confidence in the technology is surely at least partly due to the influence of Sebra―an employee of PacBio for five years before coming to New York―and Genetics Department Chair Eric Schadt, at one time PacBio’s Chief Scientific Officer.

Even here, the sequencers typically can’t be used to help treat patients, as the instruments are sold for research use only. Mount Sinai is still working on a limited number of tests to submit as diagnostics to New York State regulators.

Physician Use

Roche Diagnostics, which invested $75 million in the development of the Sequel, wants to change that. The company is planning to release its own, modified version of the instrument in the second half of 2016, specifically for diagnostic use. Roche will initially promote the device for clinical studies, and eventually seek FDA clearance to sell it for routine diagnosis of patients.

In an email to Diagnostics World, Paul Schaffer, Lifecycle Leader for Roche’s sequencing platforms division, wrote that the new device will feature an integrated software pipeline to interpret test results, in support of assays that Roche will design and validate for clinical indications. The instrument will also have at least minor hardware modifications, like near field communication designed to track Roche-branded reagents used during sequencing.

This new version of the Sequel will probably not be the first instrument clinical labs turn to when they decide to start running NGS. Short-read sequencers are sure to outcompete the Roche machine on price, and can offer a pretty useful range of assays, from co-diagnostics in cancer to carrier testing for rare genetic diseases. But Roche can clear away some of the biggest barriers to entry for hospitals that want to pursue long-read sequencing.

Today, institutions like Mount Sinai that use PacBio typically have to write a lot of their own software to interpret the data that comes off the machines. Off-the-shelf analysis, with readable diagnostic reports for doctors, will make it easier for hospitals with less research focus to get on board. To this end, Roche acquired Bina, an NGS analysis company that handles structural variants and other PacBio specialties, in late 2014.

The next question will be whether Roche can design a suite of tests that clinical labs will want to run. Long-read sequencing is beloved by researchers because it can capture nearly complete genomes, finding the correct order and orientation of DNA reads. “The long-read technologies like PacBio’s are going to be, in the future, the showcase that ties it all together,” Sebra says. “You need those long reads as scaffolds to bring it together.”

But that envisions a future in which doctors will want to sequence their patients’ entire genomes. When it comes to specific medical tests, targeting just a small part of the genome connected to disease, Roche will have to content itself with some niche applications where PacBio stands out.

Early Applications

“At this time we are not releasing details regarding the specific assays under development,” Schaffer told Diagnostics World in his email. “However, virology and genetics are a key focus, as they align with other high-priority Roche Diagnostics products.”

Genetic disease is the obvious place to go with any sequencing technology. Rare hereditary disorders are much easier to understand on a genetic level than conditions like diabetes or heart disease; typically, the pathology can be traced back to a single mutation, making it easy to interpret test results.

Some of these mutations are simply intractable for short-read sequencers. A whole class of diseases, the PolyQ disorders and other repeat disorders, develop when a patient has too many copies of a single, repetitive sequence in a gene region. The gene Huntingtin, for example, contains a long stretch of the DNA code CAG; people born with 40 or more CAG repeats in a row will develop Huntington’s disease as they reach early adulthood.

These disorders would be a prime target for Roche’s sequencer. The Sequel’s long reads, spanning thousands of DNA letters at a stretch, can capture the entire repeat region of Huntingtin at a stretch, unlike short-read sequencers that would tend to produce a garbled mess of CAG reads impossible to count or put in order.

Nonetheless, the length of reads is not the only obstacle to understanding these very obstinate diseases. “The entire category of PolyQ disorders, and Fragile X and Huntington’s, is really important,” says Sebra. “But to be frank, they’re the most challenging even with PacBio.” He suggests that, even without venturing into the darkest realms of the genome, a long-read sequencer might actually be useful for diagnosing many of the same genetic diseases routinely covered by other instruments.

That’s because, even when the gene region involved in a disease is well known, there’s rarely only one way for it to go awry. “An example of that is Gaucher’s disease, in a gene called GBA,” Sebra says. “In that gene, there are hundreds of known mutations, some of which you can absolutely genotype using short reads. But others, you would need to phase the entire block to really understand.” Long-read sequencing, which is better at distinguishing maternal from paternal DNA and highlighting complex rearrangements within a gene, can offer a more thorough look at diseases with many genetic permutations, especially when tracking inheritance through a family.

“You can think of long-read sequencing as a really nice way to supplement some of the inherited panels or carrier screening panels,” Sebra says. “You can also use PacBio to verify variants that are called with short-read sequencing.”

Virology is, perhaps, a more surprising focus for Roche. Diagnosing a viral (or bacterial, or fungal) infection with NGS only requires finding a DNA read unique to a particular species or strain, something short-read sequencers are perfectly capable of.

But Mount Sinai, which has used PacBio in pathogen surveillance projects, has seen advantages to getting the full, completely assembled genomes of the organisms it’s tracking. With bacteria, for instance, key genes that confer resistance to antibiotics might be found either in the native genome, or inside plasmids, small packets of DNA that different species of bacteria freely pass between each other. If your sequencer can assemble these plasmids in one piece, it’s easier to tell when there’s a risk of antibiotic resistance spreading through the hospital, jumping from one infectious species to another.

Viruses don’t share their genetic material so freely, but a similar logic can still apply to viral infections, even in a single person. “A virus is really a mixture of different quasi-species,” says Sebra, so a patient with HIV or influenza likely has a whole constellation of subtly different viruses circulating in their body. A test that assembles whole viral genomes—which, given their tiny size, PacBio can often do in a single read—could give physicians a more comprehensive view of what they’re dealing with, and highlight any quasi-species that affect the course of treatment or how the virus is likely to spread.

The Broader View

These applications are well suited to the diagnostic instrument Roche is building. A test panel for rare genetic diseases can offer clear-cut answers, pointing physicians to any specific variants linked to a disorder, and offering follow-up information on the evidence that backs up that call.

That kind of report fits well into the workflows of smaller hospital labs, and is relatively painless to submit to the FDA for approval. It doesn’t require geneticists to puzzle over ambiguous results. As Schaffer says of his company’s overall NGS efforts, “In the past two years, Roche has been actively engaged in more than 25 partnerships, collaborations and acquisitions with the goal of enabling us to achieve our vision of sample in to results out.”

But some of the biggest ways medicine could benefit from long-read sequencing will continue to require the personal touch of labs like Mount Sinai’s.

Take cancer, for example, a field in which complex gene fusions and genetic rearrangements have been studied for decades. Tumors contain multitudes of cells with unique patchworks of mutations, and while long-read sequencing can pick up structural variants that may play a role in prognosis and treatment, many of these variants are rarely seen, little documented, and hard to boil down into a physician-friendly answer.

An ideal way to unravel a unique cancer case would be to sequence the RNA molecules produced in the tumor, creating an atlas of the “transcriptome” that shows which genes are hyperactive, which are being silenced, and which have been fused together. “When you run something like IsoSeq on PacBio and you can see truly the whole transcriptome, you’re going to figure out all possible fusions, all possible splicing events, and the true atlas of reads,” says Sebra. “Cancer is so diverse that it’s important to do that on an individual level.”

Occasionally, looking at the whole transcriptome, and seeing how a mutation in one gene affects an entire network of related genes, can reveal an unexpected treatment option―repurposing a drug usually reserved for other cancer types. But that takes a level of attention and expertise that is hard to condense into a mass-market assay.

And, Sebra suggests, there’s another reason for medical centers not to lean too heavily on off-the-shelf tests from vendors like Roche.

Devoted as he is to his onetime employer, Sebra is also a fan of other technologies now emerging to capture some of the same long-range, structural information on the genome. “You’ve now got 10X Genomics, BioNano, and Oxford Nanopore,” he says. “Often, any two or even three of those technologies, when you merge them together, can get you a much more comprehensive story, sometimes faster and sometimes cheaper.” At Mount Sinai, for example, combining BioNano and PacBio data has produced a whole human genome much more comprehensive than either platform can achieve on its own.

The same is almost certainly true of complex cases like cancer. Yet, while companies like Roche might succeed in bringing NGS diagnostics to a much larger number of patients, they have few incentives to make their assays work with competing technologies the way a research-heavy institute like Mount Sinai does.

“It actually drives the commercialization of software packages against the ability to integrate the data,” Sebra says.

Still, he’s hopeful that the Sequel can lead the industry to pay more attention to long-read sequencing in the clinic. “The RS II does a great job of long-read sequencing, but the throughput for the Sequel is so much higher that you can start to achieve large genomes faster,” he says. “It makes it more accessible for people who don’t own the RS II to get going.” And while the need for highly specialized genetics labs won’t be falling off anytime soon, most patients don’t have the luxury of being treated in a hospital with the resources of Mount Sinai. NGS companies increasingly see physicians as some of their most important customers, and as our doctors start checking into the health of our genomes, it would be a shame if ubiquitous short-read sequencing left them with blind spots.

Source: http://diagnosticsworldnews.com/2015/12/16/long-read-sequencing-age-genomic-medicine.aspx

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Integrated R&D Informatics & Knowledge Management, February 10-12, 2014 | Moscone North Convention Center | San Francisco, CA

Posted in Computational Biology/Systems and Bioinformatics, Technology Transfer: Biotech and Pharmaceutical, Translational Science, tagged AstraZeneca, Big data, Biogen Idec, Research & Development, Roche on December 9, 2013| Leave a Comment »

Cambridge Healthtech Institute’s Sixth Annual

Integrated R&D Informatics & Knowledge Management

Supporting Collaboration, Externalization, Globalization & Translational Research

February 10-12, 2014 | Moscone North Convention Center | San Francisco, CA

Reporter: Aviva Lev-Ari, PhD, RN

For the past five years, Integrated R&D Informatics & Knowledge Management has brought together senior executives and leaders in R&D informatics from pharma, large biotech and their partners to discuss the latest ways to manage the integration of data from disparate sources to create valuable knowledge for their organizations. This year’s conference will focus on addressing how informatics teams are enabling and supporting internal collaboration along with externalization of data, helping deal with pre-competitive activities, as well as continuing to support translational research, all directed at the overall goal of improving productivity and efficiency in a cost-effective manner.

Day 1 | Day 2 | Day 3 | Download Brochure

Monday, February 10

10:30 am Conference Program Registration

EXTERNAL COLLABORATION BEST PRACTICES: GETTING VALUE OUT OF DATA WITH YOUR COLLABORATORS

11:50 Chairperson’s Opening Remarks

Martin Leach, Vice President, Research & Development IT, Biogen Idec

12:00 pm Roche’s Translational and Clinical Research Center (TCRC): How Our Big Data and Externalization Strategy Impacts Drug Discovery

Juergen Hammer, Ph.D., MBA, Pharma Research and Early Development Informatics (pREDi), pREDi Center Head; Global Head, Disease & Translational Informatics, Roche Translational Clinical Research Center

Pharmaceutical companies increasingly embed their research and early development organizations into vibrant academic hubs to enhance innovation and asset finding. Roche has recently opened “TCRC, Inc.”, soon to be located in New York City. The presentation will focus on our Big Data and Externalization approaches to support the TCRC, and will exemplify how we impact drug development decisions using informatics.

12:30 The Lilly Open Innovation Drug Discovery Program (OIDD)

Daniel H. Robertson, Ph.D., Senior Director, LRL IT Research, Eli Lilly and Company

Through OIDD, Lilly has established a network of top global research talent at academic and biotech institutions to provide them access to proprietary, in vitro phenotypic, and target-based assays (PD2 and TargetD2). In addition to supplying data that may lead to potential collaborations, Lilly has recently been partnering to deploy additional design tools for OIDD investigators to assist in designing compounds submitted to the assays through this collaboration.

1:00 Session Break

Sponsored by

1:15 Luncheon Presentation I: Building and Linking Disease and Drug Target Profiles Using Semantic Search Technologiesnt

Maria Shkrob, Ph.D.,Senior Bioinformatics Scientist, Elsevier

Researchers face a growing challenge in managing vast quantities of unstructured data to find relevant information that can guide their research. A new semantic search engine that incorporates text-mining capability along with customizable dictionaries and taxonomies rapidly finds facts and provides summary tables from multiple sources, including scientific abstracts and full-texts, grant applications, and in-house documents. This ability to accurately retrieve and summarize information significantly increases researcher productivity compared to traditional keyword search.

1:45 Luncheon Presentation II (Sponsorship Opportunity Available)

2:15 Session Break

2:30 Chairperson’s Remarks

Martin Leach, Vice President, Research & Development IT, Biogen Idec

2:35 Building an Informatics Ecosystem for Externalized R&D

Sándor Szalma, Ph.D., Head, External Innovation, R&D IT, Janssen Research & Development, LLC

Pharma companies have historically been involved in many partnerships fueling their discovery engines, supported with non-optimal IT systems. With recent wide-spread adaptation of hosted solutions and cloud computing, there is an opportunity now to implement informatics solutions such that collaborative exploration of the data generated in partnerships becomes possible. We also discuss the opportunities to build parts of the ecosystem in a pre-competitive manner and our experience in deploying open source tools.

3:05 Cloud Solutions Spanning Applications across R&D, Development, G&A, and Compliance Functions

John Reynders, CIO, Moderna Therapeutics; former Vice President, Research & Development Information, AstraZeneca

This presentation will overview Moderna’s aggressive push into cloud solutions spanning applications across R&D, development, G&A, and compliance functions. Moderna’s cloud-based informatics workflows for the design, development, screening, and delivery of messenger RNA therapeutics will be shared along with associated challenges of Big Data, cloud security, collaboration, and cross-cloud integration.

3:35 PANEL DISCUSSION: Approaches and Lessons Learned to Build a Comprehensive R&D Search Capability

Martin Leach, Vice President, Research & Development IT, Biogen Idec

The accessibility of information within any R&D organization is key to the successful collaboration and development of a research pipeline. The holy grail for most research organizations is the one-stop search (aka. Google-like search for R&D). In this panel we will discuss the approaches a number of research organizations have taken, successes, failures and lessons learned.

Panelists:

John Koch, Director, Scientific Information Architecture & Search, Merck

Hongmei Huang, Ph.D., Director, NIBR IT, Novartis

Sponsored by

4:05 Efficient Data Mining for Precision Medicine
Sirimon O’Charoen, Ph.D., Manager, Translational Medicine, Life Sciences Professional Services, Thomson Reuters

4:35 Refreshment Break and Transition to Plenary Keynote

5:00 Plenary Keynote Session (Click Here For More Details)

6:15 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:45 Close of Day

Tuesday, February 11

7:00 am Registration and Morning Coffee

8:00 Plenary Keynote Session (Click Here For More Details)

Sponsored by

9:15 Refreshment Break in the Exhibit Hall with Poster Viewing

REGISTRATION SYSTEMS

10:25 Chairperson’s Remarks

Arturo J. Morales, Ph.D., Global Lead, Biology Platform Informatics, Novartis Institutes for Biomedical Research

10:30 Registration Systems: Applications or Data Stores?

Arturo J. Morales, Ph.D., Global Lead, Biology Platform Informatics, Novartis Institutes for Biomedical Research

Registration systems are not applications that usually stand on their own. Their value comes from the enablement of downstream data analysis and sample tracking through proper management of concept and sample metadata. As such, most registration systems offer little intrinsic value to those that use it directly and user compliance can be a challenge. Thus, it is important to adapt to workflows, as opposed to making users adapt to them.

11:00 Development of a LIMS Platform to Manage Biological Therapeutics

David M. Sedlock, Ph.D., Senior Director, Research & Development Systems, Takeda Cambridge US

The management of biological samples for testing as biotherapeutic agents requires a unique type of LIMS to handle both workflows and sample registration. We are currently engaged in a couple of projects at Takeda to create a working solution for both research and preclinical development samples to be managed across multiple R&D sites. The project status and business impact will be reviewed.

11:30 An Enhanced Electronic Laboratory Notebook to Support Biologics Research and Development

Beth Basham, Ph.D., Director, Account Management, Biologics Discovery & IT Site Lead, Merck

Merck is evolving our electronic lab notebook from a straightforward paper notebook replacement to a platform that structures data and results, provides basic LIMS-like capabilities and enables powerful search and analytics. We will share our experiences in providing a solution to support some of the stages of biologics research and development.

12:00 pm Biological Registration Systems at UCB and How They Integrate into the Discovery Workflow

David Lee, Ph.D., Principal Scientist, Informatics, UCB

The benefits of informatics-driven data management systems are well known in the small molecule therapeutics arena. Extending these systems to supporting biotherapeutics presents a number of challenges. We present a novel data management system, BioQuest, integrating bespoke and best in class software systems designed to capture and integrate NBE data at UCB. We will focus on registration systems, in particular on the antibody and non-antibody protein registration system based on the Genedata Biologics platform.

12:30 Session Break

Sponsored by

12:40 Luncheon Presentation I

Speaker to be Announced

1:10 Luncheon Presentation II (Sponsorship Opportunity Available)

1:40 Refreshment Break in the Exhibit Hall with Poster Viewing

PRE-COMPETITIVE COLLABORATION & SUPPORTING PUBLIC-PRIVATE PARTNERSHIPS

2:15 Chairperson’s Remarks

Barry Bunin, Ph.D., CEO, Collaborative Drug Discovery (CDD, Inc.)

Sponsored by

2:20 Modern Drug Research Informatics Applications to CNS, Infectious, Neglected, Rare, and Commercial Diseases

Barry Bunin, Ph.D., CEO, Collaborative Drug Discovery (CDD, Inc.)

There are currently hundreds of commodity technologies for handling scientific information – each with its own scope and limitations. The application of collaborative technologies to interrogate potency, selectively, and therapeutic windows of small molecule structure activity relationship (SAR) data will be presented in 5 case studies. Given external (public and collaborative) data grows faster than internal data, novel collaborative technologies to gracefully manage combined external and private data provide an ever-increasing competitive advantage.

2:50 tranSMART: Use Cases from Deployments Highlighting Emerging Models for Pre-Competitive Collaboration and Open Source Sustainability

Dan Housman, CTO, Translational Research, Recombinant By Deloitte

The tranSMART open source translational research knowledge management software continues to make forward progress since the initial release in 2012. Specific use cases from a variety of projects incorporating tranSMART will be walked through to highlight emerging pre-competitive collaboration models including opportunities, new capabilities, and unresolved challenges. The current state of open project sustainability and approaches taken by Recombinant and other groups to ensure the software increases in value for adopters will be explored.

3:20 The Innovative Medicines Initiative: Collaborating around Knowledge Management

Anthony Rowe, Ph.D., Principal Scientist, External Innovation, Johnson & Johnson

The Innovative Medicines Initiative (IMI) is a public-private partnership between the European Federation of Pharmaceutical Industry and Associates (EFPIA) and the European Union. It is dedicated to overcoming key bottlenecks in pharmaceutical research by enabling pre-competitive collaboration between industry and academic scientists. In this talk we will review the Knowledge Management activities undertaken by the IMI and how they are delivering new services and capabilities that can enhance pharmaceutical R&D.

Sponsored by

3:50 Bringing Scientific Data to Life: Agile Data Access and Analysis from Discovery to Development

Jonathan Feldmann, Vice President, Scientific Informatics, Certara

4:20 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing

5:20 Breakout Discussions in the Exhibit Hall

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Collaboration, Externalization and Privacy

Micahel H. Elliott, CEO, Atrium Research & Consulting

At what extent is data exchange required in the era of R&D virtualization?
How do we balance ollaboration with security risk?
What tools are required to enable virtualization? Will these be vendor supplied or custom?

Biological Registration Systems

Arturo J. Morales, Ph.D., Global Lead, Biology Platform Informatics, Novartis Institutes for Biomedical Research

How do we implement systems that users want to use?
What are some good practices?
Where are data standards making a difference?

Data Integration Today

Ajay Shah, Ph.D., Director, Research Informatics, City of Hope National Medical Center

Building extensible software platform for integrating basic, clinical and translational research data – technology, data and cultural challenges
Integrating deeper analysis and natural language processing tools to leverage the platform for translational research
Case studies from participants and discussion

Translational Informatics

Shoibal Datta, Director, Data Sciences, Biogen Idec

What does the perfect translational informatics platform look like and how do we get there?
Where does translation stop?
What does the Affordable Care Act mean to the future of Real World Evidence

6:30 Close of Day

Wednesday, February 12

7:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Plenary Keynote Session (Click Here For More Details)

9:45 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

DATA INTEGRATION & SHARING: TOOLS AND POLICIES FOR VISUALIZATION AND ANALYSIS

10:35 Chairperson’s Remarks

Larry Hunter, Ph.D., Director, Center for Computational Pharmacology & Computational Bioscience Program, Professor, Pharmacology, University of Colorado

10:40 Knowledge-Based Analysis at Genomic Scale

Larry Hunter, Ph.D., Director, Center for Computational Pharmacology & Computational Bioscience Program, Professor, Pharmacology, University of Colorado

High-throughput instruments and the explosion of new results in the scientific literature is both a blessing and a curse to the bench researcher. Effective design and implementation of computational tools that genuinely facilitate the generation of novel and significant scientific insights remains poorly understood. This talk presents efforts that combine natural language processing for information extraction, graphical network models for semantic data integration, and some novel user interface approaches into a system that has facilitated several significant discoveries.

11:00 Combining Visual Analytics and Parallel Computing for Data-Driven Analysis Pipeline Selection and Optimization to Support the Big Data to Knowledge Transformation

Richard Scheuermann, Director, Informatics, J. Craig Venter Institute

This presentation describes our efforts at the J. Craig Venter Institute (JCVI) in collaboration with the Texas Advanced Computing Center (TACC) in the development of a high performance cyber-infrastructure that combines visual analytics and parallel computing for data-driven selection and optimization of analytical pipelines based on objective performance metrics. We demonstrate the application of these principles and infrastructure for the analysis of genome-wide gene expression and high-throughput, high dimensional flow cytometry data in clinical and translational research settings.

11:20 Real World Evidence for Pharma: Improving Traditional Research by Enhancing Real World Data Environment

Arpit Davé, Director, IT, Bristol-Myers Squibb

Life sciences organizations have started to change the way they discover, develop, and commercialize medicines to address patient, regulators and payer needs at every stage of the product lifecycle. Real world data (longitudinal and integrated patient information) is the key to answering complex questions in R&D and product commercialization. In order to access patient data across boundaries, companies and regulators are experimenting with various data and analytics collaboration models. This talk presents key lessons learned.

11:40 Spotfire Templates for Analysis & Visualization of Project Data

Sandhya Sreepathy, PMP, Head of Operations, Global Discovery Chemistry, Novartis

There has been a significant increase in the usage of Spotfire by project teams in Emeryville for visualization and analysis of data. To help streamline development activity and support the needs of project teams with data analysis and visualization, NIBR-IT in collaboration with computational chemistry group in Emeryville developed project based Spotfire templates. Templates were built leveraging existing technologies for retrieval/import of data and incorporated common elements of analysis and visualization(scaffold assignment, ligand, lipophilic efficiency, activity ratios, r-group decomposition etc). Predefined visualizations and filters helped accelerate project team decision making.

12:10 pm Session Break

12:20 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:00 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing

HOW BIG DATA WILL DRIVE RESEARCH FORWARD

1:40 Chairperson’s Remarks

Michael H. Elliott, CEO, Atrium Research & Consulting LLC

1:45 Harnessing Big Data to Accelerate Drug Development

Vinod Kumar, Ph.D., Senior Investigator, Computational Biology, GlaxoSmithKline Pharmaceuticals

With the rapid development of high-throughput technologies and ever-increasing accumulation of whole genome-level datasets, an increasing number of diseases and drugs can be comprehensively characterized by the changes they induce in gene expression, protein, metabolites and phenotypes. Integrating and querying such large volumes of data, often spanning domains and residing in diverse sources, constitutes a significant obstacle. This talk presents two distinct approaches that utilize these data types to systematically evaluate and suggest new disease indications for new and existing drugs.

2:15 Drug Process Design Improvement based on Data Management and Analysis

Valérie Vermylen, Knowledge Management, Director, GPS, UCB

Most of the scientific process data generated are not free to access, even if managed in databases. At UCB, data was recently made available including its context. It allows process developers to draw easily designed space and define critical parameters. To support investigation studies as impact analysis, manufacturing dashboards and trends are automatically published. An example of correlation between process data and patients’ clinical responses will be presented as an illustration of advanced data analysis.

2:45 The Library of Integrated Network-based Cellular Signatures (LINCS) Information FramEwork (LIFE)

Stephan C. Schürer, Ph.D., Associate Professor, Pharmacology, Center for Computational Science at Miller School of Medicine, University of Miami

The NIH-funded LINCS consortium is producing an extensive dataset of cellular response signatures to a variety of small molecule and genetic perturbations. We have been developing the LINCS Information FramEwork (LIFE) – a specialized knowledge-driven search system for LINCS data.

Sponsored by

3:15 An Enhanced Molecular Design Platform That Fosters Ideation, Knowledge Transfer, and Collaboration

John Conway, Enterprise Informatics, Schrödinger, Inc.

Drug discovery is the ultimate team sport. Schrödinger is developing a collaborative and knowledge engineered platform—LiveDesign—to help scientists not only capture their ideas and best practices, but to exploit and share these with select team members. Above and beyond the aggregation of 2D data, this platform will allow users to bring together 3D data with its associated annotations. LiveDesign will ultimately lead to better patient outcomes, promoting better scientific communication by exposing data, ideas, and colleague feedback during the design and redesign phases of molecular discovery.

3:45 Refreshment Break

FROM BIG DATA TO TRANSLATIONAL INFORMATICS

4:00 Chairperson’s Remarks

Shoibal Datta, Ph.D., Director, Data Sciences, Biogen Idec

4:05 Designing and Building a Data Sciences Capability to Support R&D and Corporate Big Data Needs

Shoibal Datta, Ph.D., Director, Data Sciences, Biogen Idec

To achieve Biogen Idec’s strategic goals, we have built a cross-disciplinary team to focus on key areas of interest and the required capabilities. To provide a reusable set of IT services we have broken down our platform to focus on the Ingestion, Digestion, Extraction and Analysis of data. In this presentation, we will outline how we brought focus and prioritization to our data sciences needs, our data sciences architecture, lessons learned and our future direction.

4:35 Translational Informatics: Decomposing to Singularity

John Shon, M.D., Head, Translational Informatics IT, Johnson & Johnson

There has been an explosion of data across discovery, development, and beyond and all informatics groups are struggling with major challenges in computation, storage and analysis. In a large pharmaceutical environment, the value propositions of informatics lie primarily in three dimensions which I describe. In the larger hyperdynamic environments of research technologies, information technologies, and modern science, interdisciplinary and collaborative approaches become imperative to execute translational strategies effectively.

5:05 Integrating Translational Research Tools

Erik Bierwagen, Ph.D., Principal Programmer Analyst, Department of Bioinformatics, Genentech, Inc.

This talk will cover our efforts at creating an integrated informatics system for animal studies from birth to death and beyond. Our efforts span many different disciplines and groups, but share the common effort of integrating data seamlessly.

5:35 Close of Conference Program

SOURCE

http://www.triconference.com/Discovery-Informatics/

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Non-small Cell Lung Cancer drugs – where does the Future lie?

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, FDA Regulatory Affairs, International Global Work in Pharmaceutical, Medical and Population Genetics, Pharmaceutical Analytics, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Uncategorized, tagged adenocarcinoma, advance therapy, Alimta, American Cancer Society, angiogenesis, avastin, Bevacizumab, Carboplatin, Chemotherapy, Cisplatin, dacomoitinib, EGFR, EGFr kinase, epidermal growth factor, erlotinib, FDA, first-line maintenance therapy, Genentech, KRAS, large cell carcinoma, Lung cancer, lymph nodes, metastasis, Methotrexate, Non-small cell lung cancer, Non-small-cell lung carcinoma, NSCLC, OSI pharmaceutical, PF-00299804, Pfizer, PFS, progression-free survival, quinazoline, Roche, SJC pharmaceutical, Squamous-cell carcinoma, tarceva on November 6, 2012| 21 Comments »

Non-small Cell Lung Cancer drugs – where does the Future lie?

In focus: Tarceva, Avastin and Dacomitinib

UPDATED on July 5, 2013

(from reports published in New England Journal of Medicine on drug, crizotinib)

Curator: Ritu Saxena, Ph.D.

Introduction

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and usually grows and spreads more slowly than small cell lung cancer.

There are three common forms of NSCLC:

Adenocarcinomas are often found in an outer area of the lung.
Squamous cell carcinomas are usually found in the center of the lung next to an air tube (bronchus).
Large cell carcinomas can occur in any part of the lung. They tend to grow and spread faster than the other two types.

Lung cancer is by far the leading cause of cancer death among both men and women. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. The American Cancer Society’s most recent estimates for lung cancer in the United States for 2012 reveal that about 226,160 new cases of lung cancer will be diagnosed (116,470 in men and 109,690 in women), and there will be an estimated 160,340 deaths from lung cancer (87,750 in men and 72,590 among women), accounting for about 28% of all cancer deaths.

Treatment

Different types of treatments are available for non-small cell lung cancer. Treatment depends on the stage of the cancer. For patients in whom the cancer has not spread to nearby lymph nodes are recommended surgery. Surgeon may remove- one of the lobes (lobectomy), only a small portion of the lung (wedge removal), or the entire lung (pneumonectomy). Some patients require chemotherapy that uses drugs to kill cancer cells and stop new cells from growing.

FDA approved drugs for NSCLC

Abitrexate (Methotrexate)
Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation)
Alimta (Pemetrexed Disodium)
Avastin (Bevacizumab)
Bevacizumab
Carboplatin
Cisplatin
Crizotinib
Erlotinib Hydrochloride
Folex (Methotrexate)
Folex PFS (Methotrexate)
Gefitinib
Gemcitabine Hydrochloride
Gemzar (Gemcitabine Hydrochloride)
Iressa (Gefitinib)
Methotrexate
Methotrexate LPF (Methotrexate)
Mexate (Methotrexate)
Mexate-AQ (Methotrexate)
Paclitaxel
Paclitaxel Albumin-stabilized Nanoparticle Formulation
Paraplat (Carboplatin)
Paraplatin (Carboplatin)
Pemetrexed Disodium
Platinol (Cisplatin)
Platinol-AQ (Cisplatin)
Tarceva (Erlotinib Hydrochloride)
Taxol (Paclitaxel)
Xalkori (Crizotinib)

On the basis of target, the drugs have been classified as follows:

NSCLC Drug Market Analysis

NSCLC drug market expected to grow from $4.2 billion in 2010 to $5.4 billion in 2020

Although, a whole list of agents is available for the treatment of NSCLC, the market for NSCLC drugs is expected to expand from $4.2 billion in 2010 to $5.4 billion in 2020 in the United States, France, Germany, Italy, Spain, the United Kingdom and Japan.

However, drug sales for metastatic/advanced squamous cell non-small-cell lung cancer, which comprises only a small fraction of the market, will decrease from nearly 17 percent in 2010 to approximately 13 percent in 2020. According to surveyed U.S. oncologists and MCO pharmacy directors, increasing overall survival is one of the greatest unmet needs in first-line advanced squamous non-small-cell lung cancer.

In 2009, antimetabolites dominated the NSCLC market, with Eli Lilly’s Alimta (Pemetrexed) accounting for nearly three-quarters of sales within this drug class. Since then, Alimta has faced tough competition from a number of similar drugs and from emerging therapies. It was speculated that the antimetabolites market share would reduce significantly making it the second-largest drug class in NSCLC, while the epidermal growth factor receptor (EGFR) inhibitor class will garner the top market share by 2019.

Genentech/OSI Pharmaceuticals/Roche/Chugai Pharmaceutical’s Tarceva belongs to the EGFR inhibitor class, and has been prescribed principally along with Eli Lilly’s Alimta, to NSCLC patients.Both these drugs have dominated the NSCLC market till 2010, however, their market hold is expected to weaken from 2015-2020, as claimed by Decision Resources Analyst Karen Pomeranz, Ph.D. Decision Resources is a research and advisory firms for pharmaceutical and healthcare issues.

Tarceva (Erlotinib)

Generic Name: Erlotinib, Brand Name: Tarceva

Other Designation: CP 358774, OSI-774, R1415, RG1415, NSC 718781

Mechanism of Action: Tarceva, a small molecule quinazoline, directly and reversibly inhibits the epidermal growth factor receptor (EGFr) tyrosine kinase. Detailed information on how it works could be found at the Macmillian Cancer support website.

Tarceva has been approved for different cancers and several indications have been filed-

non-small cell lung cancer (nsclc), locally advanced or metastatic, second line, after failure of at least one prior chemotherapy regimen (2004)
pancreatic cancer, locally advanced or metastatic, in combination with gemcitabine, first line (2005)
non-small cell lung cancer (nsclc), advanced, maintenance therapy in responders following first line treatment with platinum-based chemotherapy (2010)
non-small cell lung cancer (nsclc) harboring epidermal growth factor (EGFr)-activating mutations, first line treatment in advanced disease

Sales of Tarceva

May, 2012 sales of Tarceva in the US have been reported to be around $564.2 million.

In a recent article published by Vergnenègre et al in the Clinicoeconomic Outcomes Research journal (2012), cross-market cost-effectiveness of Erlotinib was analyzed. The study aimed at estimating the incremental cost-effectiveness of Erlotinib (150 mg/day) versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease.

It was determined that treatment with erlotinib in first-line maintenance resulted in a mean life expectancy of 1.39 years in all countries, compared with a mean 1.11 years with best supportive care, which represents 0.28 life-years (3.4 life-months) gained with erlotinib versus best supportive care.

According to the authors analysis, there was a gain in the costs per-life year as $50,882, $60,025, and $35,669 in France, Germany, and Italy, respectively. Hence, on the basis of the study it was concluded that Erlotinib is a cost-effective treatment option when used as first-line maintenance therapy for locally advanced or metastatic NSCLC.

Avastin (Bevacizumab)

Generic Name: Avastin, Brand Name: Bevacizumab

Other Designation: rhuMAb-VEGF, NSC-704865, R435, RG435

Mechanism of Action

Bevacizumab is a recombinant humanized Mab antagonist of vascular endothelial growth factor A (VEGFA) acting as an angiogenesis inhibitor.

Targets

Vascular endothelial growth factor (VEGF, VEGF-A, VEGFA)

Avastin is the only currently approved VEGF inhibitor that selectively targets VEGF-A.

Three other approved oral drugs, pazopanib (Votrient; GlaxoSmithKline), sunitinib (Sutent; Pfizer) and sorafenib (Nexavar; Onyx Pharmaceuticals) are orally available multi-targeted receptor tyrosine kinase inhibitors that include VEGF receptors among their targets.

Avastin has been approved for different cancers and several indications have been filed:

colorectal cancer, advanced, metastatic, first line, in combination with a 5-FU based chemotherapy regimen
colorectal cancer, relapsed, metastatic, second line, in combintion with 5-FU-based chemotherapy (2004)
non-small cell lung cancer (nsclc), non-squamous, inoperable, locally advanced, recurrent or metastatic, in combination with carboplatin and paclitaxel chemotherapy, first line (2006)
breast cancer, chemotherapy naive, first line, locally recurrent or metastatic, in combination with taxane chemotherapy (2008, revoked in 2011)
non-small cell lung cancer (nsclc), non-squamous, inoperable, locally advanced, recurrent or metastatic, in combination with platinum-based chemotherapy, first line
renal cell carcinoma (RCC), metastatic, in combination with interferon (IFN) alpha, first line (2009)
glioblastoma multiforme (GBM), relapsed after first line chemoradiotherapy
breast cancer, chemotherapy naive, first line, locally recurrent or metastatic, HEr2 negative, in combination with capecitabine (2009)
ovarian cancer, in combination with standard chemotherapy (carboplatin and paclitaxel) as a first line treatment following surgery for women with advanced (Stage IIIb/c or Stage IV) epithelial ovarian, primary peritoneal or fallopian tube cancer
ovarian cancer, in combination with carboplatin and gemcitabine as a treatment for women with recurrent, platinum-sensitive ovarian cancer

SOURCE:

New medicine Oncology Knowledge Base

Sales of Avastin

As of May, 2012, sales of Avastin in the US have been reported to be around $2.66 billion.

It attracted a lot of attention over the past few years after its use as a breast cancer treatment. Avastin was approved by the FDA under its fast-track program. However, the data released by the FDA from follow-up studies led to questioning the use of Avastin as a breast cancer drug. Infact, Genentech pulled the indication from Avastin’s label. Henceforth, the FDA did cancel that approval in late 2011. Doctors, however, can still prescribe it off-label. Potential adverse effects of Avastin that came under scrutiny along with unfavorable cost benefit analyses might pose challenges to its growth potential and continued widespread use. However, the sales of Avastin have continued to increase and it has been reported by Fierce Pharma as one of the 15 best-selling cancer drugs list. (Fierce Pharma)

Dacomitinib: New promising drug for NSCLC

Generic Name: Dacomitinib

Other Designation: PF-299804, PF-00299804, PF-299,804, PF00299804

PF-299804 is an orally available irreversible pan-HEr tyrosine kinase inhibitor.

Dacomitinib is a promising new drug on the market. Phase III trials are ongoing for advanced and refractory NSCLC, locally advanced or metastatic NSCLC and the EGFr mutation containing locally advanced or metastatic NSCLC in several countries including those in Europe, Asia, and America.

SOURCE:

New medicine Oncology Knowledge base

Dacomitinib bests Erlotinib in advanced NSCLC: Comparison of its Progression-Free Survival (PFS) with the NSCLC marketed drug, Erlotinib.

In September of 2012, a study was published by Ramalingam et al in the Journal of Clinical Oncology, which was a randomized open-label trial comparing dacomitinib with erlotinib in patients with advanced NSCLC. On the basis of the study it was concluded that dacomitinib demonstrated significantly improved progression-free survival (PFS*) as compared to erlotinib, with a certain degree of toxicity.

SOURCE:

Randomized Phase II Study of Dacomitinib Versus Erlotinib in Patients With Advanced Non-Small-Cell Lung Cancer

The results indicated indicated the following:

Median PFS was significantly greater with Dacomitinib than Erlotinib, at 2.86 versus 1.91.
Mean duration of response was 16.56 months for dacomitinib and 9.23 months for erlotinib.

Patients were divided into groups by tumor type and following results were obtained:

Median PFS was 3.71 months with dacomitinib and 1.91 with erlotinib in patients with KRAS wild-type tumors
Median PFS was 2.21 months and 1.68 months, in patients with KRAS wild-type/EGFR wild-type tumors.
PFS was significantly better in the molecular subgroups harboring a mutant EGFR genotype.

The study also highlighted the side effects which might be more of concern and probably limiting for Dacomitinib.

Although adverse side effects were uncommon in both the groups, certain side effects such as:

mouth sores,
nailbed infections, and
diarrhea

were more common and tended to be more severe with Dacomitinib as compared to Tarceva.

Therefore, for patients for whom side effects of Tarceva seem challenging might face more difficulty with Dacomitinib treatment. Nonetheless, the results of PFS were promising enough and provide a greater efficacy in several clinical and molecular subgroups targeting a larger population than Tarceva. Authors, thus, suggested a larger, randomized phase III trial with the same design.

Current status of Dacomitinib

Based on positive performance of Dacomitinib published in research studies, Pfizer has entered into a collaborative development agreement with the SFJ Pharmaceuticals Group to conduct a phase III clinical trial across multiple sites in Asia and Europe, to evaluate dacomitinib (PF-00299804) as a first line treatment in patients with locally advanced or metastatic non-small cell lung cancer (nsclc) with activating mutations in the epidermal growth factor receptor (EGFr). Under the terms of the agreement, SFJ will provide the funding and clinical development supervision to generate the clinical data necessary to support a registration dossier on Dacomitinib for marketing authorization by regulatory authorities for this indication. If approved for this indication, SFJ will be eligible to receive milestone and earn-out payments.

SOURCE:

New medicine Oncology Knowledge base

*PFS or Progression-free survival is defined as the length of time during and after the treatment of as disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.

REFERENCES

New medicine Oncology Knowledge base Information on clinical trials, drug indications, sales report, drug target, manufacturing companies
Lung cancer statistics from Cancer.org.
NSCLC FDA approved drugs
The pharmaletter NSCLC drug marketanalysis
Decision resources news on Lung Cancer drugs
Research article- cross-market cross-effectiveness of erlotinib
Macmillian Cancer Support – Tarceva
Fierce Pharma – Tarceva
Fierce Pharma – Avastin
Research article- Randomized Phase II Study of Dacomitinib Versus Erlotinib in Patients With Advanced Non-Small-Cell Lung Cancer
Medical net news- PFS boosted by dacomitinib
Onclive publications- Dacomitinib bests Erlotinib in NSCLC
Cancergrace- Dacomitinib shows survival benefits vs tarceva
Pharmaletter- Pfizer links with SJC pharma for dacomitinib trials

Recently, another drug PF-02341066 (crizotinib), was tested on patients with non-small cell lung cancer and the results were published in New England Journal of Medicine (2013). Crizotinib is an orally available aminopyridine-based inhibitor of the) and the c-Met/hepatocyte growth factor receptor (HGFR). Crizotinib, in an ATP-competitive manner, binds to and inhibits ALK kinase and ALK fusion proteins. In addition, crizotinib inhibits c-Met kinase, and disrupts the c-Met signaling pathway. Altogether, this agent inhibits tumor cell growth.

Shaw and colleagues (2013) investigated whether crizotinib is superior to standard chemotherapy with respect to efficacy. To answer the question, Pfizer launched a phase III clinical trial (NCT00932893; http://clinicaltrials.gov/show/NCT00932893) comparing the safety and anti-tumor activity of PF-02341066 (crizotinib) versus pemetrexed or docetaxel in patients with advanced non-small cell lung cancer harboring a translocation or inversion event involving the ALK gene. Shaw and colleagues (2013) published the results of the clinical trial in a recent issue of New England Journal of Medicine. A total of 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen were recruited for the trial and patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. According to the results, the median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group. Hazard ratio (HR) for progression or death with crizotinib was 0.49 (95% CI, P<0.001). The response rates were 65% with crizotinib, as compared with 20% with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy.In conclusion, the results from the trial indicate that crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non–small-cell lung cancer with ALK rearrangement. (Shaw AT, et al, Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med 2013; 20 June, 368:2385-2394; http://www.ncbi.nlm.nih.gov/pubmed/23724913).

However, in the same issue of New England Journal of Medicine, Awad and colleagues (2013) reported from a phase I clinical trial (NCT00585195; http://clinicaltrials.gov/show/NCT00585195), that a patient with metastatic lung adenocarcioma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment, showed resistance to crizotinib. Biopsy of the resistant tumor identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. The study was funded by Pfizer (Awad MM, et al, Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med. 2013 Jun 20;368(25):2395-401; http://www.ncbi.nlm.nih.gov/pubmed/23724914)

Reference:

Shaw AT, et al, Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med 2013; 20 June, 368:2385-2394; http://www.ncbi.nlm.nih.gov/pubmed/23724913
Awad MM, et al, Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med. 2013 Jun 20;368(25):2395-401; http://www.ncbi.nlm.nih.gov/pubmed/23724914
Trial number: NCT00932893; http://clinicaltrials.gov/show/NCT00932893
Trial number: NCT00585195; http://clinicaltrials.gov/show/NCT00585195
National Cancer Institute (NCI) drug dictionary: Crizotinib, http://www.cancer.gov/drugdictionary?CdrID=586080

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Personalized Medicine as Key Area for Future Pharmaceutical Growth

Posted in Alzheimer's Disease, Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, BioSimilars, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, FDA Regulatory Affairs, Genome Biology, Genomic Testing: Methodology for Diagnosis, Health Economics and Outcomes Research, Health Law & Patient Safety, Innovations in Neurophysiology & Neuropsychology, International Global Work in Pharmaceutical, Medical and Population Genetics, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy and Cell Activity, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Scientist: Career considerations, Technology Transfer: Biotech and Pharmaceutical, tagged BRAF, Food and Drug Administration, National Institute for Health and Clinical Excellence, Personalized medicine, Roche, Roche Holding, Severin Schwan, Vemurafenib on September 18, 2012| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

During Investor Day, Roche Highlights Personalized Medicine as Key Area for Future Growth

September 12, 2012

By Turna Ray

As regulators and payors around the world are demanding more evidence that healthcare products improve patient outcomes and save money, Roche this week attempted to reassure investors that its strategy to develop innovative products — with a strong focus on molecularly guided personalized medicines — will place it ahead of competitors.

Through several presentations during an investor day in London, Roche officials highlighted a number of drugs for cancer, neuropsychiatric conditions, and autoimmune diseases for which the company is investigating biomarkers that can help target treatment to specific groups of patients. The company said that more than 60 percent of the compounds in its drug pipeline are currently paired with a companion diagnostic and that it has more than 200 companion diagnostic projects underway across its pharma and diagnostic business groups.

Personalized medicines are not only a major part of Roche’s plan for future growth, but they also represent a way for the company to differentiate its products from competitors. By setting its drugs apart from other me-too treatments in the marketplace, the company is hoping that its products won’t be as heavily affected by the pricing pressures currently plaguing the pharma and biotech sectors.

“Yes, regulators are very stringent. But if I look back at our most recent launches, particularly in the US, if you have true medical innovation, then regulators are very willing to bring those medicines and novel diagnostics to the market,” Roche CEO Severin Schwan said during the investor conference. He highlighted that the US Food and Drug Administration reviewed and approved the BRAF inhibitor Zelboraf for metastatic melanoma and its companion diagnostic in record time and that the recent approval of the HER2-targeted breast cancer drug Perjeta also occurred ahead of schedule (PGx Reporter 8/17/2011 and 6/13/2012).

“Likewise, if you look at the payors, there is cost pressure,” Schwan reflected, but he noted that the “innovative nature” of its portfolio helps it to “negotiate better prices with payors.”

Despite this optimistic forecast, Roche has experienced some pushback from cost-conscious national payors in Europe. For example, in June the UK’s National Institute for Health and Clinical Excellence deemed Zelboraf, which costs more than $82,000 for a seven-month treatment, too pricey. Zelboraf, which Roche launched in the US market last year and in European countries earlier this year, netted the company around $97 million in revenue for the six months ended June 30.

In an effort to battle pushback from national payors, Roche is in discussions with European governments about value-based pricing schemes for several of its products. In this regard, high priced personalized medicine drugs are well suited to these types of arrangements. David Loew, chief marketing officer at Roche, told investors that governments are increasingly developing registries to track how individual patients are doing on various treatments. This information will help governments move from a volume-based pricing model for drugs to paying for them based on the drug’s indication.

He noted that in Germany, for example, Roche has developed a payment scheme where in colorectal cancer, patients pay a certain amount for up to 10 grams of the oncologic Avastin, receive it for free for up to 12 months, and then the scheme repeats. For personalized medicines, such as Herceptin, Perjeta, T-DM1, and Zelboraf, “we will have to think about different ways of pricing those new combinations,” Loew said.

Schwan highlighted that one of the major advantages for Roche in this difficult environment is that it has both drug and diagnostic capabilities in house. This, according to Schwan, enables Roche to have significant internal capabilities in early-phase research, and makes the company attractive for partnerships, as well. Roche currently has more than 70 new molecular entities in clinical development and since 2011 there have been 25 late-stage clinical trials that have yielded positive results. The firm plans to bring three more products into late-stage clinical trials by the end of the year and would like to move 10 products into late-stage development in 2013.

On the diagnostics side, newly hired chief operating officer Roland Diggelmann said that Roche is aiming to grow its presence in the testing market by becoming “the partner of choice” for developing companion assays and collaborating internally with Roche pharma to advance personalized medicine.

“We need to make sure that science translates into great medicines by designing trials that take smart risk into account, that really focus on ensuring that the molecules are being developed in the right diseases; to make sure we have the right dose; to make sure, whenever possible, we have the … companion diagnostic strategies,” Chief Medical Officer Hal Barron said at the meeting. “This whole strategy needs to result in a higher probability of success so that the return on investment is above the cost of capital and an important driver for our business.”

While Roche plans on identifying new product opportunities through a mix of its internal capabilities and external collaborations, growth through large mergers and acquisitions – a strategy that other large pharmaceutical companies have readily utilized to expand product portfolios – doesn’t seem to be a priority at the company. Noting that there may be opportunities for smaller M&A deals, Alan Hippe, chief financial and information technology officer, noted that at Roche, “we are not big fans of big mergers and big M&A.”

Targeting Cancer

A large portion of Roche’s personalized medicine strategy will be directed toward oncology, where the company has allocated 50 percent of its research and development budget.

In June, the FDA approved Perjeta in combination with Herceptin and decetaxel chemotherapy as a treatment for metastatic breast cancer patients whose tumors overexpress the HER2 protein. The agency simultaneously also approved two companion tests that can help doctors discern best responders to the treatment (PGx Reporter 6/13/2012).

Herceptin (trastuzumab), approved in 1998, still comprises a big chunk of Roche’s therapeutics business, contributing 11 percent of the $18.2 billion the firm netted in overall drug sales in the first half of the year. Roche is hoping to preserve earnings from this blockbuster drug — often hailed as the first personalized medicine success story — by combining it with Perjeta and linking it with a derivative of the chemotherapy maytansine, DM1.

Recently, Roche announced data from a late-stage clinical trial called EMILIA that showed that advanced breast cancer patients receiving the antibody drug conjugate trastuzumab emtansine, or T-DM1, lived “significantly” longer than those treated with a combination of Genentech’s Xeloda (capecitabine) and GlaxoSmithKline’s Tykerb (lapatinib). The patients in EMILIA had to have progressed after initial treatment with Herceptin and taxane chemotherapy.

According to Loew, the company is currently conducting a study looking at T-DM1 as a potential option for first-line metastatic breast cancer patients. In addition, Roche is also studying T-DM1 as an adjuvant treatment in early-stage breast cancer patients with residual disease; comparing T-DM1 plus Perjeta against Herceptin plus Perjeta in the adjuvant early-stage breast cancer setting; and looking at T-DM1-based chemotherapy in the neoadjuvant setting.

“So if we are successfully delivering those results, I think the HER2-positive breast cancer space has been completely changed and redefined,” Loew told investors.

At the end of the year, another study, called the Protocol of Herceptin Adjuvant with Reduced Exposure, or PHARE, is slated to report results, and the outcome could have a negative impact on Herceptin sales. PHARE is comparing whether patients given Herceptin for 12 months, which is currently the standard of care in the US, fare better than those given the drug for six months.

Industry observers have projected that Perjeta and T-DM1 could be a sufficient buffer against a scenario in which six months of Herceptin is found to be non-inferior to a year of the drug.

Barron noted that Roche is readily applying the strategy behind antibody-drug conjugates such as T-DM1 – where antibodies to attach to antigens on the surface of cancer cells to localize chemotherapy delivery and reduce adverse reactions – in 25 projects across its portfolio. He added that antibody-drug conjugates offer a promising mechanism for personalizing treatments.

In non-small cell lung cancer, Roche is studying MetMab (onartuzumab) in combination with Tarceva in patients with tumors that overexpress the Met protein. Data from this Phase III trial, called METLUNG, is expected in 2014. Data from a Phase II study looking at MetMab and Tarceva as a second-line NSCLC treatment yielded negative results when all comers were considered. However, the subgroup of patients who over-expressed Met had a “doubling” of progression-free survival and a “pronounced” effect on overall survival compared to the low-Met group.

Roche is also investigating MetMab in metastatic gastric cancer (Phase III), triple-negative breast cancer, (Phase II), metastatic colorectal cancer (Phase II), glioblastoma (Phase II), as well as in combination with Avastin in various cancer indications.

Other Areas of Personalization

Outside of oncology, Roche is exploring biomarker strategies to personalize drugs for Alzheimer’s disease and schizophrenia. Phase I data from a study involving gantenerumab, a IgG1 monoclonal antibody, suggest that the drug could potentially reduce amyloid plaque in Alzheimer’s patients’ brains.

Investigational drugs targeting beta-amyloid, which many researchers believe to be involved in the pathogenesis of Alzheimer’s disease, haven’t fared well in clinical trials. Most recently, Johnson & Johnson/Pfizer’s drug bapineuzumab, which also targeted the β-amyloid protein, failed to benefit Alzheimer’s patients who were non-carriers of APOE4 gene variations.

Wall Street analysts are hoping that Roche’s biomarker-driven strategy for gantenerumab will help it avoid a similar fate. The company is currently conducting a 770-patient trial called Scarlet Road, in which researchers will measure Tau/Aβ levels in study participants’ spinal fluid to identify early onset or prodormal Alzheimer’s patients and treat them with gantenerumab. Roche is developing a companion test to gauge Tau/Aβ levels in trial participants. Results from Scarlet Road are expected in 2015.

Roche subsidiary Genentech is testing another compound, crenezumab, to see if it can prevent Alzheimer’s in a population genetically predisposed to getting the disease. Genentech, in collaboration with Banner Alzheimer’s Institute and the National Institutes of Health, is conducting a Phase II trial investigating crenezumab in the residents of Medellin, Colombia, where people share a common ancestor and have a high prevalence of mutations in the presenelin 1 gene. Those harboring the dominant gene mutation will start to lose their memory in their mid-40s and their cognitive functions will deteriorate by age 50.

The five-year study will involve approximately 300 participants, of whom approximately 100 mutation carriers will receive crenezumab and another 100 mutation carriers will receive a placebo. In a third arm, approximately 100 participants who don’t carry the mutations will receive a placebo. Study investigators will begin recruiting patients for this study next year.

In schizophrenia, Roche is exploring bitopertin, a glycine reuptake inhibitor, in six Phase III studies slated for completion next year. Three of these studies are looking at the drug’s ability to control negative symptoms in schizophrenia, while the other three trials are studying the drug’s impact on sub-optimally controlled disease symptoms. “A companion diagnostics assay is in development to validate the hypothesis for an exploratory biomarker predicting response to therapy with bitopertin,” Roche said in a statement.

For lupus, Roche is conducting a proof of concept Phase II trial involving rontalizumab, an anti-interferon-alpha antibody, in which researchers are using a biomarker to identify patients most likely to respond to the drug. Data from this trial will be presented at a medical conference later this year.

Growing Role of Diagnostics

Daniel O’Day, who served as CEO of Roche Molecular Diagnostics until last week when he was appointed chief operating officer of the company’s pharma division, valued the worldwide diagnostics market at $53 billion. “We represent 20 percent of that, or around 10 billion Swiss francs ($11 billion),” he said in his investor day presentation.

While molecular diagnostics promise to be a growing part of Roche’s business in the coming years, these products currently only represent a single-digit percent of Roche’s overall diagnostics business. For the first half of this year, molecular diagnostics comprised around 6 percent of Roche’s diagnostics sales of $5.3 billion.

Roche’s Ventana Medical Systems subsidiary will likely play a large role in advancing Roche’s presence in the companion diagnostics space. This year, Ventana announced it was developing companion tests for a number of drug makers, including Aeterna Zentaris, Syndax Pharmaceuticals, Pfizer, and Bayer (PGx Reporter 1/18/2012).

In addition to these external collaborations, Roche officials highlighted the company’s internal diagnostics capabilities as particularly advantageous for expanding its presence in the personalized medicine space. For example, Roche developed the BRAF companion test for Zelboraf. The company is also developing a companion EGFR-mutation test for its non-small cell lung cancer drug Tarceva in the first-line setting, and a test to gauge so-called “super-responders” to the investigational asthma drug lebrikizumab being developed by Genentech.

In terms of molecular diagnostics, O’Day highlighted a test that gauges the overexpression of the p16 gene in cervical Pap test samples to gauge whether women have precancerous lesions.

Additionally, the FDA this year approved the use of Ventana’s INFORM HER2 Dual ISH DNA Probe cocktail on the BenchMark ULTRA automated slide staining platform, which allows labs to analyze fluorescent in situ hybridization and immunohistochemistry samples in one assay. According to O’Day, this test has been more successful than standard FISH tests in identifying HER2 status in difficult-to-diagnose patients. The company will be publishing data on this test soon, showing that it can “identify about 4 percent more [HER2-postiive patients] than FISH alone.”

When it comes to molecular technologies, Roche, like other pharma and biotech players, appear to be sticking to tried and tested technologies, such as IHC, FISH, and PCR, and reserving whole-genome sequencing for research use. “Today, sequencing is predominantly a research tool. And it’s a very valuable research tool in the future,” O’Day said, estimating that sequencing-based tests will “go into the clinic” in the next half decade.

Turna Ray is the editor of GenomeWeb’s Pharmacogenomics Reporter. She covers pharmacogenomics, personalized medicine, and companion diagnostics. E-mail her here or follow her GenomeWeb Twitter account at @PGxReporter.