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Posts Tagged ‘GlaxoSmithKline’

Author and Reporter: Anamika Sarkar, Ph.D.

Targeted therapies are proven approaches in Cancer and other complicated diseases. Degrees of activation of measured EGFR and ERB2/HER2 in cancer cells are thought of one of the ways to identify the scale of aggressiveness of cancer in tissues.  There are drugs, mostly for breast cancer, which targets inhibition of these receptors. Lapatinib (Tykerb, GSK – see Source for other targeted drugs) is the first drug which inhibits both EGFR and ERB2/HER2 gave hope to cancer patients, especially advanced ERB2-postive or metastatic breast cancer patients. Despite of proven high efficacy, Lapatinib didn’t show promising results in clinical responses due to acquired resistance.

Komurov et. al. (Mol. Systems.Biol., 2012) used network analysis along with experimental findings on cultured human breast cancer cell lines (SKBR3) and showed that a large part of acquired resistance to Lapatinib is due to  increased levels of activated states of glucose deprivation signaling network. The authors cultured ERB2-positive SKBR3 cells with increasing doses of Lapatinib, to make the control cell lines for analyzing their experimental results in comparison with (SKBR3- R),SKBR3-Resistant cells. Their Western Blot analysis showed that Lapatinib was successful to inhibit down signaling pathways to ERB2 and EGFR in both control and resistant cells however fails to induce apoptotic pathways in resistant cells when compared with the controlled cells.

To identify other factors which can influence the differential effects of Lapatinib on controlled and resistant cell lines, Komurov et. al. used a data biased random walk network analysis method called Netwalk (Komurov et. al. PLOS Comp Biol., 2010). Their method is data driven and based on comparative network analysis of gene expressions at different conditions rather than network analysis at one gene level. Their network analysis identified presence of high levels of genes which act as compensatory mechanisms for glucose deprivation (as shown in Figure 2 of the paper Komurov et. al. (2012) Figure 2). They showed validation of their network analysis findings using Western Blot analysis (as shown in Figure 3 of the paper Komurov et.al. (2012) Figure 3).

 

The authors’ results not only show a nice elegant way of finding new information using network analysis and experimental techniques together, but also points out an important concept which can be future of cancer therapy. Their results show that along with targeting mutated Oncogenes eg., EGFR and ERB2/HER2 as in case of Lapatinib, additional way of controlling the pathway of deprivation of glucose, can achieve better clinical responses for cancer patients with aggressive levels of cancer. Targeting glucose or pathways of glucose can be tricky, because of its ubiquitous links to many physiological functions, including metabolism. However, the levels at which these pathways need to be targeted to achieve certain positive responses at in-vitro, supported by systems biology methods, and then in-vivo studies can be informative.  Moreover, targeting many parts in the network in smaller amounts, along with targeted cancer drugs, may produce interesting results.

Sources:

Komurov et.al. (2012) : http://www.ncbi.nlm.nih.gov/pubmed/22864381

A News and Views on Lapatinib (2005) : http://www.emilywaltz.com/Herceptin.pdf

Komurov et.al. (2010) – Article published on methods of Netwalk : http://www.ncbi.nlm.nih.gov/pubmed/20808879

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Reporter: Aviva Lev-Ari, PhD, RN

Ten Biotech Powerhouses Such as Abbott Laboratories (ABT),AstraZeneca PLC (AZN) Unite to Form TransCelerate BioPharma Inc. to Accelerate the Development of New Meds

TransCelerate – New Non-Profit Organization to Speed Pharmaceutical R&D,  headquartered in Philadelphia

“This initiative is complementary to efforts of CTTI, and we look forward to working with TransCelerate BioPharma to improve the conduct of clinical trials.”
As shared solutions in clinical research and other areas are developed, TransCelerate will involve industry alliances including:

9/19/2012 9:29:28 AM

PHILADELPHIA, Sept. 19, 2012 /PRNewswire/ — Ten leading biopharmaceutical companies announced today that they have formed a non-profit organization to accelerate the development of new medicines. Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Pfizer, Genentech a member of the Roche Group, and Sanofi launched TransCelerate BioPharma Inc. (“TransCelerate”), the largest ever initiative of its kind, to identify and solve common drug development challenges with the end goals of improving the quality of clinical studies and bringing new medicines to patients faster.

 

Through participation in TransCelerate, each of the ten founding companies will combine financial and other resources, including personnel, to solve industry-wide challenges in a collaborative environment. Together, member companies have agreed to specific outcome-oriented objectives and established guidelines for sharing meaningful information and expertise to advance collaboration.

“There is widespread alignment among the heads of R&D at major pharmaceutical companies that there is a critical need to substantially increase the number of innovative new medicines, while eliminating inefficiencies that drive up R&D costs,” said newly appointed acting CEO of TransCelerate BioPharma, Garry Neil, MD, Partner at Apple Tree Partners and formerly Corporate Vice President, Science & Technology, Johnson & Johnson. “Our mission at TransCelerate BioPharma is to work together across the global research and development community and share research and solutions that will simplify and accelerate the delivery of exciting new medicines for patients.”

Members of TransCelerate have identified clinical study execution as the initiative’s initial area of focus. Five projects have been selected by the group for funding and development, including: development of a shared user interface for investigator site portals, mutual recognition of study site qualification and training, development of risk-based site monitoring approach and standards, development of clinical data standards, and establishment of a comparator drug supply model.

As shared solutions in clinical research and other areas are developed, TransCelerate will involve industry alliances including Clinical Data Interchange Standards Consortium (CDISC), Critical-Path Institute (C-Path), Clinical Trials Transformation Initiative (CTTI), Innovative Medicines Initiative (IMI), regulatory bodies including the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), and Contract Research Organizations (CROs).

Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research, said, “We applaud the companies in TransCelerate BioPharma for joining forces to address a series of longstanding challenges in new drug development. This collaborative approach in the pre-competitive arena, utilizing the collective experience and resources of 10 leading drug companies and others to follow, has the promise to lead to new paradigms and cost savings in drug development, all of which would strengthen the industry and its ability to develop innovative and much-needed therapies for patients.”

“These leading pharmaceutical companies are in a position to significantly influence changes in the way that clinical trials are done, so that better answers about the benefits and risks of drugs and other therapies are provided in a more efficient manner,” said Robert Califf, MD, Co-Chair of CTTI and Director of the Duke Translational Medicine Institute. “This initiative is complementary to efforts of CTTI, and we look forward to working with TransCelerate BioPharma to improve the conduct of clinical trials.”

TransCelerate BioPharma evolved from relationships fostered via the Hever Group, a forum for executive R&D leadership to discuss relevant issues facing the industry and solutions for addressing common challenges. TransCelerate was incorporated in early August 2012 and will file for non-profit status this fall. The Board of Directors includes R&D heads of ten member companies. Membership in TransCelerate is open to all pharmaceutical and biotechnology companies who can contribute to and benefit from these shared solutions. TransCelerate’s headquarters will be located in Philadelphia, PA.

http://news.bms.com/press-release/rd-news/ten-pharmaceutical-companies-unite-accelerate-development-new-medicines-0&t=634836499683795253

 

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Reporter: Aviva Lev-Ari, PhD, RN

 

HEALTH LAW, ETHICS, AND HUMAN RIGHTS

Ethical Considerations in Studying Drug Safety — The Institute of Medicine Report

Michelle M. Mello, J.D., Ph.D., Steven N. Goodman, M.D., M.H.S., Ph.D., and Ruth R. Faden, Ph.D., M.P.H.

August 22, 2012 (10.1056/NEJMhle1207160)

The tumult arising from revelations of serious safety risks associated with widely prescribed drugs, including rosiglitazone (Avandia, GlaxoSmithKline), rofecoxib (Vioxx, Merck), and celecoxib (Celebrex, Pfizer), has led to widespread recognition that improvement is needed in our national system of ensuring drug safety. Notwithstanding federal legislation in 2007 that strengthened the authority of the Food and Drug Administration (FDA) in the postmarketing period,1 critical weaknesses in the national system persist.

Central to these weaknesses are dilemmas surrounding not only the science but also the ethics of drug-safety research,2 many of which came to the fore in the heated public debate about the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) trial, which compared the cardiovascular outcomes of long-term treatment with rosiglitazone with those of pioglitazone (Actos, Takeda) in patients with type 2 diabetes.3 At the request of the FDA, an Institute of Medicine (IOM) committee, on which we served, was convened to examine the ethics and science of FDA-required postmarketing safety research. In this article, we review the key ethics findings from the committee’s May 1, 2012, report4 and offer some reflections on the challenges ahead.

LESSONS FROM THE TIDE TRIAL

In May 2008, the FDA ordered the manufacturer of rosiglitazone, GlaxoSmithKline, to conduct a trial in response to evidence from meta-analyses that rosiglitazone was associated with a higher risk of myocardial infarction and death from cardiovascular causes than placebo or medications that were not based on nonthiazolidinedione comparators.5,6 Other studies suggested that pioglitazone, an alternative thiazolidinedione, was not associated with such risks.7,8 Before enrollment began, some argued that the evidence of the inferior safety of rosiglitazone was strong enough to make the trial ethically unjustifiable. Two FDA epidemiologists wrote in a 2008 memorandum that a head-to-head trial “would be unethical and exploitative” and that even a robust informed-consent process could not overcome the problem.9 This was not the consensus FDA view, which was that the uncertainty regarding the cardiovascular risks associated with rosiglitazone, as well as those associated with pioglitazone, was sufficient to justify a trial.10

These concerns triggered a February 2010 letter from members of Congress to the FDA demanding a justification for the trial and alleging that the consent form did not provide adequate risk information.11 In response, FDA Commissioner Margaret Hamburg expanded the FDA investigation of the safety of rosiglitazone, obtained advice from an FDA advisory committee, and asked the IOM to convene our committee.6 Although the FDA advisory committee recommended that the TIDE trial be continued if rosiglitazone was permitted to remain on the market, in September 2010, the FDA halted the trial and placed stringent new restrictions on the availability of rosiglitazone.12,13

The TIDE experience made the FDA appreciate the need for greater attention to the ethics of postmarketing research. First, it posed questions about what standard of evidence about drug risk justifies a decision by the FDA to require postmarketing research, particularly randomized trials, as well as what evidence could render such trials unacceptable. Second, it raised questions about what ethical obligations the FDA has to patients who participate in these studies. Finally, it highlighted a potential FDA role in ensuring that institutional review boards (IRBs) are completely informed in their efforts to protect study participants. Although major deficiencies with the TIDE consent form were identified by some FDA scientists and, later, by the IOM committee (Table 1TABLE 1Major Deficiencies in the Informed-Consent Form for the TIDE Trial.),4,9 the TIDE investigators countered that it had been approved by “480 ethics committees and IRBs.”14 However, the language of the consent form, the trial design, and the materials supporting the justification of the trial raised a question for the IOM committee about whether these bodies adequately understood the nature of the evidence that gave rise to the trial. The IOM committee proposed a framework for evaluating the ethics of FDA-required postmarketing research15 and made a number of ethics findings and recommendations.4

Ethical Responsibilities of the FDA

The IOM committee began by noting that the public health mission of the FDA gives rise to potentially competing ethical obligations “to protect the public’s health by having strong science on which to base regulatory decisions” and “to protect participants in research that it requires.”4Requiring a postmarketing study is an ethical decision, reflecting a weighing of these values.

The committee described the conditions that must be present to justify a decision to require a postmarketing study. The FDA should require postmarketing research only when, first, the uncertainty about the benefit–risk balance of a drug is so great that a responsible decision about its regulatory status cannot be made on the basis of existing evidence; second, the research will reduce this uncertainty; third, the FDA will use the research results expeditiously to make a regulatory decision; and fourth, sufficient protections for research participants can be ensured.

The committee argued that when the FDA requires a postmarketing study, it assumes a measure of ethical responsibility for the welfare of the study participants; exercise of that responsibility cannot be handed off to contractors or the industry sponsor. The responsibility is particularly strong when the patients’ treatment is determined by the study, such as in a randomized trial, linking any adverse outcomes directly to a regulatory decision to require a study of that type. This determination led to one of the most important recommendations from the IOM committee: the responsibilities of the FDA to research participants mean that it should mandate a randomized design only if the FDA “has concluded that an observational study could not provide the necessary information [to help answer the important public health question at issue], that an RCT [randomized, controlled trial] is likely to generate the information within the necessary timeframe, and that the necessary RCT is ethically acceptable.” This recommendation comports with but adds some further conditions to the current legal authority of the FDA under the FDA Amendments Act of 2007, which empowers the agency to require a randomized trial if it cannot obtain the data it needs from an observational study.1

In light of the critiques of the TIDE trial as inherently unethical, the committee addressed the justifiability of trials in which participants may encounter a net increase in risk, as compared with ordinary clinical care, but no realistic prospect of personal benefit. It argued that such trials can be justified only if they are necessary to answer a critically important public health question, if the potential risk is acceptable and minimized, and if special safeguards are in place, including a highly explicit informed-consent process to ensure that patients understand that they are potentially shouldering additional risk solely to contribute to the public good.

Specific actions that the FDA should take to meet its ethical obligations include specifying the study design, title, end points, and primary analyses; identifying design features that it views as ethically and scientifically indispensable; and, for clinical trials, specifying a safety-monitoring scheme. The committee recommended that the FDA routinely communicate with IRBs about required postmarketing studies — for example, by issuing a letter to accompany IRB applications that conveys information that is material to the IRB’s determination of the ethics of the research, as well as providing additional communications over the life of the study as warranted by new information about the drug or by changes in professional practice. The committee also believed that the FDA was ethically obligated to actually use the findings from required studies to make timely regulatory decisions.

The IOM committee emphasized that the adequacy of the informed-consent process is only one element in the ethics of FDA-required postmarketing research. Other central, and indeed prior, features include ensuring that the selection of participants is equitable and that the level of risk to which they are exposed is acceptable. The committee also recognized, however, that there are challenges to achieving meaningful informed consent in postmarketing trials of drugs for which there is a signal indicating the possibility of drug-related harm. In such cases, there is a suspicion that the benefits of the drug may not justify its risks and often that it may have a worse benefit–risk profile than alternative drugs available to treat the same condition. The committee concluded that for postmarketing trials of such drugs, there are “heightened obligations to ensure that potential research participants understand the risks posed by study enrollment.”4 This was of particular importance for rosiglitazone, because the cardiovascular problem it appeared to cause was the same outcome that good diabetic control was supposed to improve — in other words, if this elevation in risk were real, there could be little offsetting benefit.

The committee recommended several measures to strengthen the consent process in order to maximize patients’ understanding of the context in which the trial is being conducted, including what is already known about the risks associated with the drug. The report discussed both specific disclosures in the informed-consent form and special efforts that could be made to ensure adequate comprehension of complex information regarding risks (Table 2TABLE 2Mechanisms for Strengthening the Informed-Consent Process for Postmarketing Drug-Safety Studies.). To assist IRBs, the committee recommended that the FDA issue guidance interpreting current informed-consent regulatory requirements in the context of required postmarketing studies.

STRENGTHENING POSTMARKETING RESEARCH AND ITS GOVERNANCE

Because a true picture of the benefit–risk profile of a drug only emerges over time, two different IOM committees have stressed the need for the FDA to fully embrace a “life-cycle approach” to drug regulation, in which its obligations to protect public health are taken as seriously once a drug is on the market as they are before approval is granted.4,16 Postmarketing regulatory oversight is assuming heightened importance as the FDA accrues additional authority to fast-track drugs for approval on the basis of more limited evidence than was previously required in order to address unmet medical needs and accelerate innovation.17-19 This changing landscape raises several challenges for ensuring the ethical conduct of research with approved drugs and balancing societal interests in drug innovation and drug safety. We highlight two of these challenges here.

First, not all postmarketing research is ethically equivalent. The TIDE trial represented an iconic kind of postmarketing study: an FDA-required randomized trial to study a drug whose benefit–risk profile was under a cloud of suspicion and at a time when alternative treatments were available, albeit not all well studied. The risks to patients of participating in the trial probably outweighed the prospect of direct benefit. By contrast, when the FDA requires an observational study that uses previously collected data, the clinical experience of the participants is unaffected, the risks incurred are not at the behest of the FDA, and ethical concerns are largely confined to confidentiality and the right to control one’s medical information.

Both of these scenarios can be distinguished from the context in which a phase 4 trial is required as a condition of an accelerated drug approval and is initiated soon thereafter. Here, the trial requirement is not imposed because of a newly emerging concern about a drug already in clinical use but because additional evidence is needed to confirm the initial judgment that the benefits of a new drug are likely to outweigh its risks. Often, this initial judgment is based on the use of a surrogate end point for drug benefit, not on the clinical outcomes that matter most. Especially when the new drug targets an unmet medical need, it may be in the patients’ best interest to take it, pending further timely research. The ensuing trial is undertaken to confirm the improvement in clinical outcomes predicted by the surrogate — a different epistemic and ethical situation than that in which substantial evidence suggests that the surrogate is misleading or that other harms might offset a known clinical benefit.

The volume of phase 4 and other research with FDA-approved drugs is increasing, not only because of the expanded authority of the FDA to require such research but also because of the growing volume of comparative-effectiveness research. In some cases, there may be no or little ethical difference between FDA-required postmarketing research and comparative-effectiveness research initiated by academic investigators. By contrast, a comparative-effectiveness study of two widely used drugs that is not occasioned by heightened concern about the risks of one drug relative to the other is markedly different, ethically, from a study required by the FDA to pursue a safety signal that is already of such concern that practice patterns are shifting, even if both studies use randomized designs.

These differences highlight the need for IRBs to be sensitive to the place where a study falls within the life cycle of a drug and to the reason for the research. Depending on who is initiating the research, for what reasons, and when, the same study design may have very different ramifications for the benefit–risk balance of the study and what patients need to know in order to provide meaningful informed consent. Trials that may be regarded as unethical late in the life cycle because of accumulated evidence can be much easier to initiate earlier if the need for additional research is anticipated and planned at the time of initial approval. In the case of rosiglitazone, this need could have been anticipated from preapproval data showing an adverse effect on serum lipids as well as the use of a surrogate end point (glycemic control) for a first-in-class drug.5,20

Second, the experience with rosiglitazone underscored the fragility of our current system of discovering risks associated with drugs. This system relies heavily on drug sponsors and FDA scientists to conduct safety analyses on the basis of data from clinical trials, some or all of which are not publicly available, and to release findings to the public. It has been shown repeatedly that the published record can misrepresent evidence known to the FDA.21,22 In the case of rosiglitazone, scientists from GlaxoSmithKline and the FDA had information from 42 clinical trials, of which only 7 were published and the others were inaccessible. Triggered by concerns expressed by the World Health Organization in 2006, GlaxoSmithKline conducted and shared with the FDA a meta-analysis of the safety of rosiglitazone that used these data, confirming a possibly elevated risk of ischemic events, but neither these results nor the primary trial results were shared with the public until an unrelated court settlement forced GlaxoSmithKline to release its complete clinical-trial data.23 This access led to the published meta-analysis by independent researchers that made these data and concerns public in 2007.5

It is often the work of independent scientists that has highlighted critical safety problems with approved drugs.5,24-29 Yet currently, data from premarketing studies that are submitted as part of a new drug application or a supplemental new drug application are largely shielded from release to external scientists and the public owing to concerns about a competitive disadvantage to drug sponsors.30,31 The IOM committee stopped short of calling on the FDA to increase public access to such data but recommended that the agency initiate a process to determine ways to “appropriately balance public health, privacy, and proprietary interests to facilitate disclosure” of relevant data.4 Greater transparency would better equip independent scientists to investigate early safety signals.31 Consideration should be given to making drug-safety data from clinical trials available to the public on request once the FDA has reached a decision regarding a new drug application or a supplemental new drug application or once the manufacturer has abandoned the application, unless the manufacturer can articulate a persuasive reason why it would result in competitive harm and the FDA determines that this harm outweighs the public health benefits of releasing the information.

CONCLUSIONS

The experience with rosiglitazone and the TIDE trial offers a lesson in how our current approach to the oversight of drug-safety and postmarketing research can fail both the public and the research participants. Although terminating the TIDE trial was justifiable, it left regulators with highly suggestive but nondefinitive data on the relative safety of rosiglitazone and the closest clinical alternative, pioglitazone.32

Reactive policymaking is tempting but problematic. The history of regulation of human subjects research suggests that rules that are “born in scandal and reared in protectionism”33 often fall short of providing meaningful protections to research participants and that, once adopted, regulations can ossify and become difficult to dislodge. Nevertheless, the IOM committee’s report makes a number of actionable recommendations that the FDA can implement under its existing authority.34 In addition, appointment of an independent ethics advisory board would strengthen the decision making of the FDA as it confronts emerging ethical challenges — both those arising from required postmarketing trials and those stemming from powerful new drug surveillance systems, such as the FDA’s Sentinel Initiative. As the pace of the translation of discoveries from bench to bedside continues to intensify, so too does the imperative for thoughtful ethical governance throughout the life cycle of a drug.

The views expressed in this article are those of the authors and, except where noted, do not represent the official position of the Institute of Medicine or of the committee that produced the report discussed in this article.

Drs. Faden and Goodman chaired, and Dr. Mello was a member of, the Institute of Medicine committee that produced the report discussed in this article.

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

This article was published on August 22, 2012, at NEJM.org.

We thank the other IOM committee members for contributing to some of the ideas discussed.

SOURCE INFORMATION

From the Department of Health Policy and Management, Harvard School of Public Health, Boston (M.M.M.); the Departments of Medicine and Health Research and Policy, Stanford University School of Medicine, Stanford, CA (S.N.G.); and the Berman Institute of Bioethics, Johns Hopkins University, Baltimore (R.R.F.).

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    1. 32Punthakee Z, Bosch J, Dagenais G, et al. Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial.Diabetologia 2012;55:36-45
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    1. 33Levine C. Has AIDS changed the ethics of human subjects research? Law Med Health Care 1988;16:167-173
      Medline

      34

      Food and Drug Administration. Guidance for industry: postmarketing studies and clinical trials — implementation of section 505(o)(3) of the federal Food, Drug, and Cosmetic Act. April 2011 (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM172001.pdf).

      http://www.nejm.org/doi/full/10.1056/NEJMhle1207160?query=TOC

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Reporter: Aviva Lev-Ari, PhD, RN

Regulus Therapeutics and UC San Diego to Collaborate on Angiogenic Disease Research Utilizing microRNA Technology

http://www.fiercebiotech.com/press-releases/regulus-therapeutics-and-uc-san-diego-collaborate-angiogenic-disease-resear-0

– UC Discovery Grant award to support collaborative research –

La Jolla, Calif., April 14, 2011 – Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative new medicines targeting microRNAs, today announced it is collaborating with researchers at the University of California, San Diego (UCSD) School of Medicine seeking novel treatments for angiogenic diseases using microRNA therapeutics. The research will combine Regulus’ leading microRNA platform with UCSD’s expertise in animal models of angiogenesis to discover anti-angiogenic microRNA-targeted therapies that could be rapidly translated for treatment of human disease.  The collaborative research program was the recent recipient of a UC Discovery Grant that promotes collaborations between the university’s researchers and industry partners.  Financial terms of the grant were not disclosed.

“We are pleased to collaborate with leading scientific institutes like UCSD and to provide industry support for programs such as the UC Discovery Grant,” said Hubert C. Chen, M.D., Regulus’ vice president of translational medicine. “Regulus continues to demonstrate a leadership position in the field of microRNA therapeutics and is committed to forging partnerships with leading academic and clinical laboratories to advance microRNA biology and therapeutic discovery.  Our network of nearly 30 academic collaborations assists us with the investigation of new microRNAs and supports microRNA discovery efforts that feed the Company’s pipeline.”

Angiogenesis, which is the formation of new blood vessels, is an important event that contributes to the severity of cancer, diabetes, macular degeneration, inflammatory disease and arthritis.  microRNAs have been implicated in regulating biological networks involved in angiogenesis.

“Our research published last year in Nature Medicine demonstrated that microRNA-132 functions as a novel angiogenic switch that turns on angiogenesis in quiescent endothelial cells, and that targeting with an anti-miR-132 decreases blood vessel formation,” said David A. Cheresh, Ph.D., professor of pathology in the UCSD School of Medicine, associate director for translational research at UCSD Moores Cancer Center and principal investigator on the grant. “The objective of our collaborative work with Regulus is to advance these initial discoveries and discover additional microRNAs involved in angiogenic diseases.”

The UC Discovery Grant program promotes collaborations between the university’s researchers and industry partners in the interest of supporting cutting-edge research, strengthening the state’s economy and serving the public good.

About microRNAs

The discovery of microRNA in humans during the last decade is one of the most exciting scientific breakthroughs in recent history. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. More than 700 microRNAs have been identified in the human genome, and over one-third of all human genes are believed to be regulated by microRNAs. A single microRNA can regulate entire networks of genes. As such, these molecules are considered master regulators of the human genome. microRNAs have been shown to play an integral role in numerous biological processes, including the immune response, cell-cycle control, metabolism, viral replication, stem cell differentiation and human development. Most microRNAs are conserved across multiple species, indicating the evolutionary importance of these molecules as modulators of critical biological pathways. Indeed, microRNA expression or function, has been shown to be significantly altered in many disease states, including cancer, heart failure and viral infections. Targeting microRNAs with anti-miRs, antisense oligonucleotide inhibitors of microRNAs, or miR-mimics, double-stranded oligonucleotides to replace microRNA function opens potential for a novel class of therapeutics and offers a unique approach to treating disease by modulating entire biological pathways. To learn more about microRNAs, please visit http://www.regulusrx.com/microrna/microrna-explained.php.

About Regulus Therapeutics Inc.

Regulus Therapeutics is a biopharmaceutical company leading the discovery and development of innovative new medicines targeting microRNAs. Regulus is using a mature therapeutic platform based on technology that has been developed over 20 years and tested in more than 5,000 humans. In addition, Regulus works with a broad network of academic collaborators and leverages the oligonucleotide drug discovery and development expertise of its founding companies, Alnylam Pharmaceuticals (NASDAQ:ALNY) and Isis Pharmaceuticals (NASDAQ:ISIS). Regulus is advancing microRNA therapeutics towards the clinic in several key areas including hepatitis C infection, immuno-inflammatory diseases, fibrosis, oncology and cardiovascular/metabolic diseases. Regulus’ intellectual property estate contains both the fundamental and core patents in the field and includes over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNAs for therapeutic applications. In April 2008, Regulus formed a major alliance with GlaxoSmithKline to discover and develop microRNA therapeutics for immuno-inflammatory diseases. In February 2010, Regulus and GlaxoSmithKline entered into a new collaboration to develop and commercialize microRNA therapeutics targeting microRNA-122 for the treatment of hepatitis C infection. In June 2010, Regulus and sanofi-aventis entered into the largest-to-date strategic alliance for the development of microRNA therapeutics. This alliance is focused initially on fibrosis. For more information, please visit http://www.regulusrx.com.

Forward-Looking Statements

This press release includes forward-looking statements regarding the future therapeutic and commercial potential of Regulus’ business plans, technologies and intellectual property related to microRNA therapeutics being discovered and developed by Regulus. Any statement describing Regulus’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Such forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause the results to differ materially from those expressed or implied by such forward-looking statements. Although these forward-looking statements reflect the good faith judgment of Regulus’ management, these statements are based only on facts and factors currently known by Regulus. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Regulus’ programs are described in additional detail in each of Alnylam’s and Isis’ annual report on Form 10-K for the year ended December 31, 2010, which are on file with the SEC. Copies of these and other documents are available from either Alnylam or Isis.

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

 

Microbes are tiny organisms that live everywhere—in air, soil, rock, and water. These microscopic organisms are found in plants and animals as well as in the human body. Some live in heat, while others live in freezing cold. Some microbes need oxygen to live, but others do not. Some microbes keep us healthy while others can make us sick. Indeed, the relationship between microbes and humans is delicate and complex.

 

Infectious pathogens include some viruses, bacteria, fungi, protozoa, multicellular parasites. These pathogens are the cause of disease epidemics. Their existence date back more than 3.5 billion years, placing them among the oldest living things on Earth.

 

Since the 19th century, we have known that microbes cause infectious diseases. Near the end of the 20th century, researchers began to learn that microbes also contribute to many chronic diseases and illnesses. Mounting scientific evidence strongly links microbes to some forms of cancer, coronary artery disease, diabetes, multiple sclerosis, and chronic lung diseases.

 

Recently we have come across a report on the new syndicated TrendsmemeTM Report: Infectious Disease – Antimicrobials.

 

This report was released by Medmeme, LLC and with an emphasis on three indications—pneumonia, tuberculosis, and malaria – because they command the largest R&D effort and market in infectious diseases, and also they offer a window into issues relevant broadly across the therapeutic category. Based on the number of clinical trials reported in the Medmeme database, R&D for the broad field of pneumonia is the most active of the three indications.

 

A major problem common to all three indications is drug resistance and there is a significant need for novel new treatment approaches that work by different mechanisms.

 

Medmeme CEO Mahesh Naithani says that “There’s no doubt that serious measures are necessary to overcome the huge challenges. For this, the effort of cooperation between government, science, and the industry is very important. I’m particularly referring to The Infectious Diseases Society of America, the physicians, scientists and other health care professionals who specialize in infectious diseases, working with the FDA to have it allow labeling antibiotics that fight drug-resistant strains of bacteria as “orphan drugs”, he says.

 

From this, companies may see these drugs on a faster track for approval and would be encouraged to join the effort in developing treatments. The new FDA guidelines on the design of antibiotic clinical trials are already having an impact on the pace of the progress for these innovative drugs. And the partnering in Europe of GSK, Sanofi, AstraZeneca, Johnson & Johnson, and Basilea Pharmaceutica with leading scientists to form a consortium dedicated to sharing information and development data also addresses the lack of antibiotics in the pipeline.

 

And the good work of NGO’s that will bring the successes of these efforts to the developing countries is highly needed. It’ll take all this, and more, to win the battle.

 

Read more on this report at the following URL:

 

http://www.prweb.com/releases/2012/7/prweb9727894.htm?goback=%2Egde_4346921_member_138106292

 

 

 

 

 

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Biosimilars: Financials 2012 vs. 2008

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 5/9/2026

SOURCE

From: IQVIA Institute <ma@iqvia.com>
Reply-To: IQVIA <ma@iqvia.com>
Date: Saturday, May 9, 2026 at 10:02 AM
To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu>
Subject: New Report: Biosimilar Sustainability Scorecards for Europe 2026: Overall Summary and Country Scorecards

@@@

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 1989Anemia, 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 Fragments09/24/2010 – 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.

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….

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.

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.

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.

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.
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.

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

REFERENCES

http://www.wolfgreenfield.com/files/2426_biosimilars_2_final_pdf.pdf

Read Full Post »

Reporter: Aviva Lev-Ari, PhD, RN

The Price of Togetherness

Is togetherness the latest drug? Will touchy feeliness be the answer to the pharmaceutical industry’s crisis of productivity? Collaboration certainly isn’t anything new in the life sciences, but the nature and structure of partnerships is evolving to the point that many companies are now contemplating pooling their resources…and diluting their returns.

Certainly the past decade has been marked by more partnerships between industry and academia, where there has been an effort to find a win-win solution to academia’s funding deficits and pharma’s desire to get more helping hands in early innovation.

Out of this have grown “open-source” research efforts that use pharma’s financial backing to create or aggregate data any researcher can use. Sage Bionetworks, a three-year-old Seattle-based non-profit, offers a “commons” of pooled data and resources. Merck has contributed many human and mouse disease models for open consumption. Eli Lilly has opened up its doors to compounds created at academic labs through its PD2 and other Open Innovation Drug Discovery efforts. In 2008, GlaxoSmithKline released over 300 cell lines to the National Cancer Institute’s Cancer Bioinformatics Grid, open for academics to mine. The Structural Genomics Consortium is an open-access database of 3-D protein structures that counts Lilly, GSK, NovartisPfizer, and most recently Takeda among its members and financial backers.

While these kinds of open efforts come with a series of challenges concerning ownership, consent and disclosure, and many other issues, they exist because industry increasingly recognizes that biology is too complex for any one company, even a large one, to tackle on its own.

Major drug companies have also started to innovate the way they work with venture capitalists to help nurture early research. Johnson & Johnson announced back in January that it is partnering with Polaris Venture Partners to scout out and co-invest in biotech startups–presumably structuring deals such that venture backers can find an exit without relying on the lousy IPO market. And they’re hardly alone–as I highlighted a few months ago..

But now drug companies are starting to do the unthinkable–work directly with each other. They’ve taken baby steps in this direction before, often with a focus on emerging markets and diseases not viewed as critical profit-drivers. For example, 13 major drug companies joined the Bill and Melinda Gates Foundation earlier this year to combat tropical diseases. But rather than just contributing medicine, some of the companies– Abbott, Johnson & Johnson and Pfizer–are actually collaborating on research as part of the Drugs for Neglected Diseases Initiative. All the companies are sharing compound libraries.

That’s not entirely unprecedented, but companies that have wanted to work closely together in the past have formally launched joint ventures, like the HIV-focused ViiV Healthcare venture between Pfizer and GlaxoSmithKline.

Now these cooperative efforts are broadening. One announcement made at the recent Biotechnology Industry Organization (BIO)convention is the formation of a consortium for neuroscience research between seven companies including Biogen, Abbott Labs and Merck. The stakes a fairly small, at least money-wise–each company is only pledging $250,000 at this point. But it is symbolically important that they are sharing all the costs of basic research, as well as their expertise, to try to quickly and efficiently get R&D off the ground.

While some of this newfound camaraderie might be difficult for companies dreaming of developing blockbusters and keeping all the profits to themselves, there is a silver lining. The growing demand for drugs in emerging markets means that some of these collaboratively developed drugs may eventually reach much broader audiences–meaning larger populations over which to recoup development costs, bigger opportunities for rare disease indications, and acceptable profits even if prices are forced lower. That should be some consolation.

-Karl Thiel

http://www.biospace.com/news_story.aspx?NewsEntityId=264902&type=email&source=BE_062712

More by Karl Thiel

http://www.biospace.com/news_subject_all_results.aspx?CatagoryId=40094

Picturing US-Trained PhDs’ Paths

While the US National Institutes of Health Advisory Committee to the Director’s Biomedical Workforce Working Group issued a draft report this month, detailing data it collected as well as its recommendations for the federal agency, Sally Rockey really breaks it down at her NIH Office of Extramural Research blog. “I plan to highlight some of the specific data in future posts, but first, I’d like to discuss the outcome — the conceptual framework that presents a snapshot of the biomedical research workforce, incorporating the latest available data,” she says. And she does, in an infographic that follows the career paths of the 9,000 biomedical PhDs who graduated in the US in 2009. Seventy percent of them went on to do postdoctoral research, Rockey notes.

Down the line, “looking at the career paths taken by these US-trained biomedical PhDs, we can see that fewer than half end up in academia, either in research or in teaching, and only 23 percent of the total are in tenured or tenure-track positions,” she adds. “Many other people are conducting research, however, with 18 percent in industry and 6 percent in government.”

Overall, Rockey says, the non-academic biomedical workforce is huge. “If you’re a graduate student or postdoc looking at these numbers, particularly the proportion of people in industry and government settings, it makes sense to learn as much about these career paths as possible,” she writes at Rock Talk.

http://www.genomeweb.com/careers

NIH Advisory Committee to the Director’s Biomedical Workforce Working Group Issues Draft Report

 The US National Institutes of Health Advisory Committee to the Director’s Biomedical Workforce Working Group issued a draft report this week that summarizes data it has collected and includes recommendations “that can inform decisions about training the optimal number of people for the appropriate types of positions that will advance science and promote health,” it reads.In its report, the working group emphasizes the overall purpose of its research efforts and resulting recommendations, namely “to ensure future US competitiveness and innovation in biomedical research” through proper undergraduate, graduate, and postdoctoral training and to “attract and retain the best and most diverse scientists, engineers, and physicians from around the world,” as well as domestically.When it comes to graduate education, the working group suggests that NIH cap the total number of years a grad student can be supported by NIH funds, in order to encourage timely completion of PhD studies.As for graduate career training, the working group says that because around 30 percent of biomedical PhDs work in the biotech and pharmaceutical industries — in both research and non-research positions — “their transition would be more effective if their training was better aligned with the required skill-sets for these careers.” In addition, “institutions also could be encouraged to develop other degree programs — e.g. master’s degrees designed for specific science-oriented career outcomes, such as industry or public policy … as stand-alone programs or provide sound exit pathways for PhD students who do not wish to continue on the research career track,” the group continues.For PhDs who do wish to continue on with a postdoctoral fellowship, the working group suggests that NIH “create a pilot program for institutional postdoctoral offices to compete for funding to experiment in enriching and diversifying postdoctoral training,” and adjust the current stipends for the postdocs it supports to better reflect their years of training.In addition, the group recommends that NIH double the number of Pathway to Independence (K99/R00) awards it issues and shorten the eligibility period for applying to this program from five to three years of postdoc experience to encourage more PhDs to swiftly move into independent research positions. Likewise, the group suggests that NIH also double the number of NIH Director’s Early Independence awards “to facilitate the skip-the-postdoc career path for those who are ready immediately after graduate school.”More generally, the Biomedical Workforce Working Group recommends that institutions receiving NIH funds ramp up their efforts to collect information on career outcomes of the grad students and postdocs supported by federal research grants.

Finally, the group suggests that NIH create a permanent unit in the Office of the Director that would work with the extramural research community, the National Science Foundation, and the agency’s other institutes and centers “to coordinate data collection activities and provide ongoing analysis of the workforce and evaluation of NIH policies so that they better align with the workforce needs.”

http://www.genomeweb.com/nih-advisory-committee-directors-biomedical-workforce-working-group-issues-draft

Rock Talk

Helping connect you with the NIH perspective


So, What Does the Biomedical Research Workforce Look Like?

Posted on June 22, 2012 by Sally Rockey

Update 6/27/12: The full report is now posted on the ACD website.

As I blogged last week, and most of you have heard by now, a working group of the Advisory Committee to the NIH Director (ACD) that I co-chaired with Shirley Tilghman from Princeton just completed a study of the biomedical research workforce. We reported our findings to the ACD last Thursday (you can find a link to the videocasthere).

We gathered a lot of data during this study, which are included in the report (see the ACD site for the executive summary and instructions for obtaining a copy of the full report). The data also are posted on an accompanying website. I plan to highlight some of the specific data in future posts, but first, I’d like to discuss the outcome—the conceptual framework that presents a snapshot of the biomedical research workforce, incorporating the latest available data. The framework of the PhD workforce is presented below, and a companion framework for MDs and MD/PhDs in the biomedical research workforce can be seen in the report and on the website.

First, 9,000 biomedical PhDs graduated in the US in 2009 (including basic biomedical and clinical sciences), and 70% of these went on to do postdoctoral research. As we conducted our analysis, it became clear that there are few reliable data on the number of biomedical postdoctoral researchers in the US. We lack solid information on foreign-trained postdoctoral researchers, and many postdoctoral researchers change their title as they proceed through their training, complicating the data collection. That’s why the estimate of postdoctoral researchers ranges from 37,000 to 68,000.

Looking at the career paths taken by these US-trained biomedical PhDs, we can see that fewer than half end up in academia, either in research or in teaching, and only 23% of the total are in tenured or tenure-track positions. Many other people are conducting research, however, with 18% in industry and 6% in government.

The science related non-research box includes individuals working in industry, government, or other settings who do not conduct research but are part of the scientific enterprise. Many of the career paths represented by this box contribute to the scientific research enterprise and require graduate training in biomedical science. For example, program and review officers at NIH and managers in many biotechnology companies would be included in this group. This is my box too. It’s interesting to note the 18% included in this group is made up of PhDs employed in industry (13% of the total workforce), in government (2.5%), and in other settings (2.5%). This means that all individuals working in industry (research plus non-research occupations) represent about 30% of the workforce, and all those working in government represent about 9% (more than 10,000 individuals).

That leaves 13% in non-science related occupations and 2% unemployed (this does not include retirees or those who choose not to work). These are 2008 data, the latest available from the NSF Survey of Doctoral Recipients.

If you’re a graduate student or postdoc looking at these numbers, particularly the proportion of people in industry and government settings, it makes sense to learn as much about these career paths as possible. I’m very proud that we were able to develop this framework, as it seems that for the first time we have an idea of where domestically trained biomedical researchers are going. I was quite surprised by the idea that the majority of our trainees do not end up in academia. Did this surprise you?

diagram shows the flow of college graduates through graduate and postgraduate training and into the workforce

Notes on the figure

The main sources of the original data, from which the graphs in the report were made and these numbers were derived, come from three NSF surveys: the Survey of Graduate Students and Postdoctorates, the Survey of Earned Doctorates, and the Survey of Doctorate Recipients. You can see the specific sources of each number by clicking on the relevant box on the website.

The color of the numbers reflects our confidence in the accuracy of the data: high (green), medium (yellow), or low (red). For more details see colors. In this case, the red numbers in the post-training workforce box are accurate, but the color reflects the fact that we know almost nothing about the distribution of foreign-trained PhDs in the workforce, so the overall picture is an under-estimate.

The post-training workforce boxes are color coded, with light blue denoting those in research positions and academic teaching positions. The science related non-research box is colored dark blue to indicate that many of the careers represented in this box are closely related to the conduct of biomedical research.

http://nexus.od.nih.gov/all/2012/06/22/so-what-does-the-biomedical-research-workforce-look-like/

Live Chat: Are We Training Too Many Scientists?

by Jocelyn Kaiser on 27 June 2012, 8:30 AM |
Too many graduate students and postdocs chasing too few academic jobs has led to a dysfunctional biomedical research system. That’s the conclusion of a draft report on the biomedical workforce released this month by an advisory panel to the National Institutes of Health (NIH). The panel urged taking steps to shorten young scientists’ career paths, including capping how long graduate students can receive NIH support and better preparing them for non-academic careers. The report also encourages university labs to rely more on staff scientists rather than trainees.

But is it a good idea to tinker with the research system at a time when NIH funding is tighter than ever? And given that most biomedical Ph.D.s will find a job, are there really too many?

NIH Panel Urges Steps to Control Growth in Biomedical Research Trainees

by Jocelyn Kaiser on 14 June 2012, 5:50 PM |
A glut of trainees and a dearth of academic positions in the United States is creating a dysfunctional biomedical research system, an advisory group to the National Institutes of Health (NIH) concluded today. It urged several steps be taken to bring the problem under control. NIH should cap how many years it will support graduate students, pay postdoctoral researchers more, and encourage universities to fund staff scientist positions.

The changes may appear to make research labs less productive, but in the long run will result in “a more vibrant workforce,” said Shirley Tilghman, president of Princeton University and co-chair of the panel that delivered the draft report.

The widely anticipated report comes from a working group of the NIH Advisory Committee to the Director (ACD) co-led by NIH Deputy Director for Extramural Research Sally Rockey. The panel spent a year examining available data on the number and fate of biomedical researchers through different stages of their careers, focusing on the slow pace of advancement and the often-cited fact that the average age for an investigator winning the first independent grant from NIH is 42. (The panel’s economists abandoned a plan to model the workforce—there wasn’t time or sufficient data.)

 Live Chat: Are We Training Too Many Scientists? 

In the executive summary of their draft report, the panel found that a steep rise in U.S. biomedical Ph.D.s in the past decade, more foreign postdocs, and the aging of academic faculty members make it increasingly hard for young biomedical researchers to find academic jobs. Biomedical researchers are paid less than scientists in other fields, and the low pay and long training period may make the field unattractive to the best and brightest.

To address the problem, NIH needs to make some changes, the panel says. The agency should provide supplements to training grants that help students prepare for alternatives to academic careers, such as a master’s degree geared toward an industry position. It should cap how long a graduate student can receive NIH funding at 6 years (the average length of a biomedical Ph.D. including all funding is now 6.5 years, says Rockey). NIH should find ways to shift the funding source for graduate students, most of whom are now paid out of investigators’ grants, to training grants and fellowships. The reason: such programs provide higher quality training, and their graduates tend to be more successful than those funded from grants.

Postdoctoral researchers should also be supported to a greater extent by fellowships and training grants, the panel says. And postdoc stipends should be increased—starting with the entry level, now $39,264, which should rise to $42,000—and they should receive better benefits. “We think it is scandalous how [little] postdoctoral fellows are paid,” Tilghman said.

NIH should also encourage study sections to look favorably upon research projects that employ staff scientists, and institutions should create more of these positions. There is an “urban myth” that staff scientists are less productive than graduate students, Tilghman said. In fact, she said, graduate students are productive for a couple of years but are otherwise a “drain on the system.” Staff scientists, by contrast, are “often the glue that holds your lab together.”

Although the panel did not say the overall number of trainees should decline, the recommendations, if adopted, should make the growth in the number of trainees at least slow down because “we’re making it more expensive to have those individuals,” Tilghman said.

The recommendations drew concern from at least one ACD member. Biologist Robert Horvitz, of the Massachusetts Institute of Technology in Cambridge, questioned whether NIH should make “risky” changes to the system at a time when NIH is struggling with flat budgets and record-low success rates. “Some of this makes me very nervous,” he said. But Tilghman, who headed a National Research Council panel 14 years ago that she said came to “identical conclusions,” disagreed. “The only time it’s possible to make hard decisions … is actually during tough times,” she said.

NIH Director Francis Collins said he would like see some “experiments” before making “more systemically disruptive” changes to the funding system. But, he added, this time the Tilghman panel’s recommendations “will go somewhere. I promise you that.”

Tomorrow, ScienceInsider will post a story on another draft report presented later in the ACD meeting on diversity in the biomedical research workforce.

http://news.sciencemag.org/scienceinsider/2012/06/nih-panel-urges-steps-to-control.html

Can NIH Renovate the Biomedical Workforce?

By Michael Price

June 22, 2012

“The most effective training dollars that the NIH has to expend are those in their training grants.” —Shirley Tilghman

When molecular biologist and Princeton University President Shirley M. Tilghman first sounded the alarm about the need for major overhauls to the way the United States trains its biomedical workforce in the 1998 National Academies of Science report Trends in the Early Careers of Life Scientists, many of her proposals fell on deaf ears. Fourteen years later, Tilghman is arguing again for training reform, this time as chair of the National Institutes of Health (NIH) Biomedical Research Workforce Working Group.

Last week, Tilghman presented a draft of her group’s latest report to NIH’s Advisory Committee to the Director (ACD) at NIH headquarters in Bethesda, Maryland. In the report, the group calls on NIH to divert funding from research grants to training grants for graduate students, support more postdocs on training grants, increase pay and improve benefits for postdocs, and boost the prestige and remuneration of staff scientist positions in academic labs.

At the presentation, Tilghman and the other members of the working group argued that in its present state, the graduate training system at our nation’s universities and the workforce that graduates enter into are dysfunctional and unsustainable. At the root of that dysfunction, Tilghman said, is a mismatch between the training most graduate students receive and the careers most Ph.D. graduates end up in.

Shirley Tilghman

The number of academic jobs has shrunk dramatically compared to the number of new graduates. NIH estimates that 26% of biomedical Ph.D. recipients end up in tenure-track academic positions, down from 34% in 1993; meanwhile, the proportion of nontenure-track academic positions has remained constant. The growth in jobs for Ph.D. biomedical scientists, the working group concluded, is outside academia, so new graduates must be prepared to work in other roles: in industry, in government, or in positions tangentially related to their degrees, such as science writing or policy, Tilghman said.

Shifting funds toward training

How can universities prepare graduate students better for the careers they’re most likely to wind up in? One way, Tilghman said, would be for NIH to shift funding from R01 research grants, which currently support the majority of graduate students in biomedical sciences, to NIH training grants, which are peer-reviewed by NIH for their training-related virtues. The total number of graduate students supported by NIH, the report says, should remain constant.

While the number of graduate students supported by research grants has been higher than the number supported on training grants since the early 1980s, the gap steadily widened as NIH’s research budget grew—then shot up in the early 2000s when NIH’s budget doubled over 5 years (see graph below).

CREDIT: National Institutes of Health

Research grants are far and away the most common source of funding for graduate students today. Click here to enlarge image.

The report’s authors argue that many graduate students are ill-served by this approach because it limits the ability of NIH to hold principal investigators (PIs) accountable in their roles as mentors. Without oversight, Tilghman argued, it’s easy for PIs to see and treat their graduate students as laborers rather than scientists in training. If a larger proportion of the graduate student population were supported on training grants, she said, NIH could better monitor students’ training and ensure broader exposure to careers outside of academia—and better training in the skills needed to perform well in those careers.

The members of the working group “are, I think, unanimously of the view that the most effective training dollars that the NIH has to expend are those in their training grants,” Tilghman said. “Training grants are immensely effective at inducing good behavior on the part of graduate programs. … It is the only mechanism we have to really peer review the quality of graduate training.”

Robert Horvitz

Some members of the ACD weren’t buying it. Biologist Robert Horvitz of the Massachusetts Institute of Technology in Cambridge argued that shifting funding away from R01s takes away too much autonomy from PIs. “One wants to be sure that the principal investigators, who are supposed to be doing the research, continue to have enough flexibility to be able to support the research they want to do,” he said. Taking away that flexibility, he argued, could reduce research productivity.

Other ACD members, including Haile Debas, director of the University of California Global Health Institute in San Francisco, were more supportive of the recommendations. While such a shift would be bold, Debas said, “you can also do harm by doing nothing.” He proposed that NIH launch experiments to determine whether graduate students who get industry experience during their traineeships, for example, go on to have successful careers in industry.

Judith Bond, incoming president of the Federation of American Societies for Experimental Biology (FASEB) and a biochemist at Pennsylvania State University, Hershey, also disagrees with this recommendation, saying in an interview with Science Careers that “oversight of student training should be left to the universities, not the federal government.” Bond is not a member of the ACD.

Upping postdoc pay

The situation is equally grim, if not grimmer, for postdoctoral researchers, Tilghman and her colleagues argue in the report. The report recommends that more postdocs be supported by training grants and fewer by PIs’ research grants, with the total number of NIH-supported postdocs remaining constant or perhaps decreasing.

One way of reducing the number of postdocs—and decreasing the intense competition for jobs—would be to increase postdoc salaries from $39,264 to $42,000 and provide benefits equal to those of employees at their institutions, the report says. It also recommends that NIH mandate a 4% raise before the third year of postdoctoral work and a 6% raise before the seventh. The idea, Tilghman said, would be to motivate PIs to help their postdocs move as quickly as possible into jobs rather than toil away as a postdoc.

“One of the things the committee really grappled with is: To what degree are these [people] trainees … and to what extent are they worker bees who are the producers of the research in our lab?” Tilghman said. The working group felt strongly, she said, that emphasizing training is the best way to produce well-trained future PIs.

Cato Laurencin, an ACD member and CEO of the Connecticut Institute for Clinical and Translational Science in Farmington, agreed with the working group’s postdoc recommendations. “We’ve gotten into a mindset where postdocs last 5, 6, 7 years,” he said. “After 5 or 6 years of Ph.D. training, people are spending their careers in training. I am very concerned about that.”

Bond, too, agreed with the postdoc salary recommendation. “In general, FASEB is in favor of increasing postdoc salaries. … Postdocs are essential to work in the lab, and they should be paid a living wage,” she said.

But ACD member Horvitz was skeptical. The money to raise postdoc salaries “has to come from somewhere,” he said, and given NIH’s current budget woes, it might be impractical to raise postdoc pay. If PIs were forced to make do with fewer (but better paid) postdocs, he argued, lab productivity would probably decline.

Improving the staff scientist position

One way to provide more job opportunities for Ph.D. scientists would be to increase the number and stature of staff scientists in university labs. (See “A Hidden Academic Workforce.”) One way this could be accomplished would be to have universities shoulder a larger percentage of researcher salaries than most currently do, Tilghman said. That would make the positions more stable and less vulnerable to changes in NIH budgets and competitive grant renewals.

Those salaries should also be increased, the report argues, to be commensurate with the training levels of staff scientists and their value to the lab. If the number of postdocs drops as a result of raising postdoc salaries, staff scientists could fill the gap, which should help attract talented scientists to these positions.

Finally, Tilghman recommended that NIH award grants preferentially to PIs who employ staff scientists. “When I think about the tradeoff of a graduate student for a staff scientist who is already extremely well trained, who can work without constant supervision, who can really help train the younger people in the laboratory, … I actually think we’ll be more productive,” she said.

Tough times afford opportunity

Two of the key recommendations of the report—shifting funding away from R01s to create more training grants and increasing postdoc pay and benefits—met with resistance from members of the ACD. Yet Tilghman believes that these recommendations will gain more traction with NIH leadership than when she proposed similar reforms in 1998. Times are much tougher now, she said, which makes it easier to make larger changes. “The only time when it’s going to be possible to make hard decisions that would … have a long-term, beneficial effect on all the players in the biomedical workforce is … during tough times,” Tilghman said. “Doing nothing, in my view, is not an option.”

NIH Director Francis Collins said that the ACD appeared generally supportive of the report and that NIH would collect more data, build models, and run pilot programs so that they can better predict the impact of implementing the report’s recommendations. “I do think the NIH will want to take some action here,” he said. “I like the idea of doing some experiments to get some early indications of whether the interventions are achieving the goals that we hope for. It would be a very good thing before we do something more systematically disruptive in ways that we didn’t intend.”

Michael Price is a staff writer for Science Careers.http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/201206_22/caredit.a1200069

A Hidden Academic Workforce

 By Siri Carpenter

June 08, 2012

The staff scientist role is not just a boon for universities. It is also a career destination for some of the tens of thousands of highly trained researchers who wish to remain in or close to academic research—a cadre that’s far too large for the number of available faculty positions.

On university campuses, students, postdocs, and professors are so ubiquitous that it would be easy not to notice the other Ph.D.-level professional scientists—often dubbed staff scientists—who roam the halls. Some of them work as lab managers or project directors; others direct or help operate university core facilities. Despite their low profile, staff scientists are numerous and make a major contribution to their institutions.

At the University of Wisconsin (UW), Madison, between 700 and 800 members of the academic staff are Ph.D.-level scientists, estimates Heather Daniels, chair of the university’s Academic Staff Executive Committee. For comparison, the university has 2137 faculty members in all disciplines, with a number of staff scientists comparable to the number of science faculty members. The same may well be true at other, similar universities.

Many staff scientists write grants. In fact, UW Madison staff scientists brought in $120 million to the university last year, out of a total grant portfolio worth just over $1 billion. When you include grants on which staff scientists serve as co–principal investigators (co-PIs), that figure rises to $240 million.

The staff scientist role is not just a boon for universities. It is also a career destination for some of the tens of thousands of highly trained researchers who wish to remain in or close to academic research—a cadre that’s far too large for the number of available faculty positions.

Such positions typically pay better than postdocs and sometimes about as well as assistant professor positions. At UW Madison, the minimum starting salary for an academic staff scientist is $40,055. Unfortunately, there is no mechanism for annual merit-based increases, so staff scientists typically receive raises only when the state pay plan calls for an across-the-board increase. As a result, “the longer you’re here, the more your salary tends to fall behind,” Daniels says.

Most staff scientists are grant supported, a fact that, in addition to creating job insecurity, limits the ability of staff-scientist PIs to perpetuate their own careers. According to federal rules, researchers are not allowed to use time supported by federal grants to write grants. Government auditors have interpreted the rules to stipulate that grant-funded researchers are on the clock 100% of the time, Daniels says, even if they work much longer weeks than the 40-hour standard. So whenever a staff scientist’s salary comes entirely from federal grants, federal grant writing is effectively forbidden. The solution, usually, is to find non-federal money to pay part of that salary. “It’s been a struggle for a lot of universities,” she says, “to come up with non-grant dollars to give folks time to write grants. I think researchers are feeling really constrained by this.”

On the positive side, the role of staff scientist has several benefits. Staff scientists typically travel less, work fewer nights and weekends, spend less time writing grants, and have fewer administrative responsibilities than faculty members. They seldom have formal teaching responsibilities, which some staff scientists consider a perk. Much more than postdocs, staff scientists tend to have a hand in more than one scientific project at a time.

A nonfaculty career path can also provide geographic stability, notes Alexander Pico, a staff research scientist at the Gladstone Institutes, a group of research institutes closely affiliated with the University of California, San Francisco (UCSF). “If you go with the traditional route, you have to move a lot. You have to prove yourself as a Ph.D. student in one institution, then prove yourself in another as a postdoc, and then you’re expected to continue that as faculty, proving yourself in one environment after another before you get tenure,” Pico says. “The staff position is a little more stable. I really like the working culture at Gladstone, and I would really hate to have to leave just because it’s a convention in the career path.”

Here, we profile a sampling of staff scientists from two universities—UW Madison and UCSF—who have foregone the tenure track while remaining deeply rooted in university life.

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