Pharma news highlights: licensing, clinical trial data and safety issues

Ed Silverman


Ed Silverman’s news highlights this month include issues around compulsory licensing, clinical trial data publication and drug safety.

(Continued from “Pharma news highlights: GSK, Lilly, the FDA and more”)

Since our last appearance here at pharmaphorum, the closely watched struggle over compulsory licensing heated up in India, where authorities are considering a proposal to eliminate licenses that would be granted based on the price of a brand-name medicine. This came one year after India issued the first such license allowing a generic drugmaker to make a copycat version of a patented medicine.

That decision, which granted a license to Natco for a generic version of the Bayer Nexavar cancer drug, was a game-changing moment because the Indian market is so large and could set a tone for decisions by other countries that are also seeking to make so-called essential medicines more accessible for poor citizens.

Now, though, India’s Department of Pharmaceuticals issued a new draft guidance saying once patented drugs come under proposed price controls, costs should be considered reasonable and compulsory licenses should not be issued based on affordability. Instead, a new Committee for Patented Drugs should decide prices based on what is charged elsewhere, such as in the UK, Canada and Australia.


“That decision, which granted a license to Natco for a generic version of the Bayer Nexavar cancer drug, was a game-changing moment…”


The licensing debate is far from over, though. Just a few days later, the IPAB rejected the Bayer appeal, which the drugmaker then promised to fight once more before the Indian High Court in Mumbai. “The challenges faced by the Indian healthcare system have little or nothing to do with patents on pharmaceutical products as all products on India’s essential drug list are not patented,” Bayer said.

“The limited period of marketing exclusivity made possible by patents ensures that the costs associated with the research and development of innovative medicines can be recovered.” Bayer did not walk away entirely empty handed, though. A 6 percent royalty rate that Natco was ordered last year to pay the drugmaker was reportedly increased today to 7 percent.

Issues in clinical trial data publication

How long does it take for clinical trial data to get published? The latest is answer is nearly two years, according to a research letter published in JAMA Internal Medicine. And the findings update a similar effort that was undertaken a year ago and indicate there was, essentially, no improvement in publication time.

The issue is part of a broader discussion about access to clinical research data and the extent to which such information is provided on a timely basis and, in some cases, not published at all. Any delay in publication, of course, can be a stumbling block to researchers, physicians and patients, who would otherwise benefit from having access to the information as soon as possible.

In the latest analysis, the researchers traced the time between the end of data collection for 1,336 studies and their publication in 2009. They found that the median time to publication was 21 months, in general, but that the median time to publication was 24 months among trials funded by industry compared with 20 months for trials funded by government and non- profit organizations.


“Any delay in publication, of course, can be a stumbling block to researchers, physicians and patients…”


The median time was shorter among trials enrolling 1,000 subjects or more compared with trials enrolling 100 subjects or fewer, as well as trials enrolling between 100 and 1000 subjects – 18, 20, and 23 months, respectively. The median time was 17 months among trials published in journals with an impact factor greater than 10 compared with 23 months for trials published in journals with an impact factor less than 10. Impact factor measures the average number of citations to recent articles published.

The lead co-author notes that two years is a long time. “It’s at the moment that a clinical trial is completed that its findings have the greatest potential importance to the research and clinical communities,” says Joseph Ross, an assistant professor at the Yale University School of Medicine, and one of the co-authors of the paper, which was published in JAMA Internal Medicine.

At that moment, the results can “inform future research projects and ensure that research is not redundant and… inform clinical decision making and evidence-based practice guidelines. Because these studies are taking nearly two years to become available, it is slowing the uptake of the information and slowing progress in research and clinical practice,” he said.

Further clinical trial issues

Meanwhile, the debate over disclosing clinical trial data has only intensified. AbbVie, the Abbott Laboratories spin off, filed a request for an injunction to prevent the European Medicines Agency from releasing detailed patient-level data from studies concerning its top-selling Humira rheumatoid arthritis treatment.

This occurred after two rival drugmakers made Freedom of Information requests with the EMA for “raw data” on the safety and efficacy of the medication, a multi-billion-dollar seller. The move drew swift condemnation from a growing cadre of academics, but AbbVie defended its action by saying it seeks to protect “confidential and commercially-sensitive information”.

Abbvie supports “transparency of clinical research and safety information for the benefit of patients and healthcare professionals, (but not) the disclosure of commercially confidential information that does not meaningfully contribute to the scientific review or evaluation of our products.” The US and European industry trade groups filed documents supporting AbbVie.

This happened shortly after Roche announced a new plan to increase access to such information. The drugmaker vowed to work with an “independent” group of “recognized experts” to evaluate and approve requests to access patient-level data and will also support the release of case study reports for all of its licensed medicines.

Roche did so after becoming ensnared in a spat with researchers at the Cochrane Collaboration, who have long complained they were prevented from gaining access to up-to-date efficacy information for the influenza treatment. More recent attempts to obtain data prompted a response from Roche that was decried as stonewalling and a half a loaf.


“The drugmaker vowed to work with an “independent” group of “recognized experts” to evaluate and approve requests to access patient-level data…”


Now, Roche says that an independent body will assess the validity of requests for data, which will be available in a “secured system”. From there, access to patient data will be available for trials that have been submitted with a regulatory application and will be available after regulatory reviews have been completed in the US and European Union. This process begins this year and Roche says talks are being held with other drugmakers “to see if this can be an industry-wide initiative”.

Whether other drugmakers will join is uncertain, at best. In recent weeks, both the Pharmaceutical Research &amp, Manufacturers of America and the Association of British Pharmaceutical Industry released separate statements deriding the release of patient-level data and case study reports. Both fear such a move would compromise innovation.

As for Tamiflu data, Roche says it is forming a panel of four “renowned” scientists in the field of influenza to review Tamiflu data, identify any unanswered questions and agree on a statistical analysis plan. But there are some caveats. Roche says there will be an agreement, but did not offer specifics, yet maintained it will provide access to all requested Tamiflu clinical trial data for the analyses. And three of its panelists have recently been scientific advisors or consultants to Roche, or were grant recipients.

Diabetes drug safety concerns

The latest controversy over drug safety has embroiled a group of diabetes drugs. The FDA disclosed it is evaluating unpublished new findings by academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes in patients with type 2 diabetes treated with a class of drugs called incretin mimetics.

The drugs includes Merck’s Januiva and Janumet, Byetta and Bydureon, which are marketed by Bristol-Myers Squibb, Victoza, which is sold by Novo Nordisk (NOVO), Onglyza, which is marketed by Bristol-Myers (BMY) and AstraZeneca (AZN), and Tradjenta, which is marketed by Eli Lilly (LLY) and Boehringer Ingelheim.

The drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. Pancreatitis is hardly a new concern for some of diabetes drugs, warnings were issued previously and labeling was upgraded for certain drugs. But the cancer mention is a newer development.

Moreover, the FDA move comes after a recent study in JAMA Internal Medicine raised the same concern about pancreatitis, specifically, but was quickly downplayed by physician groups and stock analysts, which questioned the study methodology.

Now, the agency is raising fresh concerns that physicians may alter treatment practice, because the FDA cited patient deaths based on examinations of pancreatic tissue specimens. For the moment, the agency did not advise practice to change, but did note that the researchers were asked to provide more information on their methodology and provide samples for further analysis.

The next ‘Pharma news highlights’ will be published in April 2013.


About the author:

Ed Silverman is a prize-winning journalist who has covered the pharmaceutical industry for the past 16 years. In addition to editing Pharmalot, he is currently an editor-at-large for Med Ad News.

Previously, he was a bureau chief for The Pink Sheet, the venerable industry newsletter, and a contributor to its sister publication, In Vivo magazine. Before that, Silverman worked as a business writer for The Star-Ledger of New Jersey, one of the nation’s largest daily newspapers, where he conceived and launched Pharmalot. During his 13-year tenure, he closely followed a variety of topics of concern to those who work for, and with, drugmakers – drug development, mergers and acquisitions, regulatory oversight, safety and pricing controversies, and marketing issues.

Prior to joining The Star-Ledger, Silverman spent six years at New York Newsday and previously worked at Investor’s Business Daily, among other newspapers. He has a master’s degree in journalism from New York University and a bachelor’s degree in accounting from Binghamton University. Tethered to his laptop and Blackberry, Silverman lives in suburban New Jersey with his wife, three children, a sizeable Labrador retriever and a sneaky beagle.

What are your thoughts on the clinical trial data publication debate?