new now next
Last week, in a surprise and, in our view, disappointing move, the FDA decided to not approve Bydureon, a once-weekly GLP-1 agonist, for use in the United States despite seemingly promising clinical trial data. The FDA has asked the makers of the drug (Amylin, Eli Lilly, and Alkermes) to perform an additional study examining the effects of higher than normal blood levels of the drug on the heart, keeping in line with the agency’s recent trend of placing increasing emphasis on the cardiovascular safety of diabetes drugs. With the time needed to conduct this study and for the FDA to review this new data, approval of Bydureon may not come until mid-2012. For further details and in-depth analysis on this decision by the FDA, please see this issue’s Learning Curve. --BK
Earlier this week, the FDA chose not to approve the weight-loss drug Qnexa. Qnexa is a combination of two currently approved drugs: phentermine, which is approved for short-term weight reduction, and topiramate, which is approved for the treatment of epilepsy and migraines. When combined, these two drugs have shown considerable promise as a treatment for long-term weight loss. Over two years, obese patients engaging in a diet and exercise regimen who were treated with Qnexa achieved 11.4% weight loss with the full dose and 10.4% with the medium dose compared to just 2.4% on placebo (in ert pills). Furthermore, Qnexa has been found to significantly reduce blood pressure, lipid (cholesterol) levels, and, in other trials for individuals with type 2 diabetes, A1c (for more details, please see NewNowNext in diaTribe issue #21). The most commonly reported side effects reported were dry mouth, constipation, altered taste, and insomnia. Although promising, the members of the FDA Advisory Committee that convened this past July to review Qnexa advised the FDA not to approve the drug over concerns with possible long-term safety issues including cardiovascular risk (due to slightly increased heart rate with Qnexa), teratogenicity (the risk for birth defects), and psychiatric problems (see NewNowNext from diaTribe issue #25 for more details). The FDA chose to follow the advice of the Advisory Committee and decided not to approve the drug. Instead, the agency has asked Vivus, the maker of the drug, to: 1) provide proof that the increased heart rate observed with the drug does not increase long-term risks for cardiovascular events (such as heart attacks and strokes); 2) provide a more complete assessment of the teratogenicity risk in pregnant women and a plan to evaluate and mitigate this risk in women; and 3) provide the complete results from the two-year phase 3 study that the company recently completed. Vivus appears confident that Qnexa will eventually gain approval and plans to submit all of the requested material within six weeks. Following submission, the FDA will take between two to six months to review the material, placing the next possible approval date within the first half of 2011.
Since the withdrawal of Meridia (sibutramine) from the market earlier in October, Xenical (orlistat) remains the only weight loss drug approved for long-term use in the United States. Yet, this drug has shown only modest efficacy in reducing weight and is associated with unpleasant side effects such as frequent, oily bowel movements. While we believe that diet and exercise should remain central to treating obesity, more tools are clearly needed to combat the ever-growing obesity epidemic. In our view, effective medications like Qnexa can fill this void and provide help to potentially millions of people who are unable to achieve adequate weight control through diet and exercise alone. We eagerly look forward to hearing the FDA’s next decision on Qnexa early next year. --BK
Following on the heels of the decision for Bydureon, the FDA also decided last week not to approve Arena Pharmaceutical’s new weight loss drug Lorqess (lorcaserin). But this move by the FDA was less surprising. The FDA’s primary concern with this weight loss drug was the development of tumors (including mammary [breast tissue] tumors and astrocytomas [brain tumors]) in mice and rats treated with the drug. Given that the drug demonstrated relatively low efficacy in its phase 3 clinical trials – between 3.0% and 3.7% weight loss after one year with the highest doses tested – the potential risks outweighed the potential benefits of the drug, in the FDA’s view. The FDA has asked Arena to conduct additional laboratory experiments to learn about the tumor promoting mechanism(s) of lorcaserin in rats, and to provide clear evidence that such risks do not exist in humans. If this cannot be done in the laboratory, a two-year cancer study in animal models and/or additional clinical trials would likely be required. Although Arena has indicated that it plans to conduct the laboratory studies, no concrete timeline on when these studies would be carried out and when the drug would likely be resubmitted to the FDA for approval have been disclosed yet. We would be interested to know how the top 10% of patients on the drug did; we understand 3-4% weight loss isn’t necessarily considered significant but we are curious about, in addition to those who did “average,” how did the best patients do? --BK
David Simmons, President and General Manager of Pfizer’s Established Products Business Unit, and Kiran Mazumdar-Shaw, Chairman and Managing Director of Biocon, shake hands, ushering the start of a new and exciting partnership.
Do you ever wonder why there aren’t cheaper “generic” insulin products available? In five to ten years time, that will most likely be the case. Patents for Lantus (sanofi-aventis’ basal insulin glargine) expire in the US in 2015, while patents for other insulin products, such as Humalog (Eli Lilly’s fast-acting insulin lispro) and Novolog (Novo Nordisk’s fast-acting insulin aspart) expire within a similar timeframe. This leaves the door wide open for other companies to introduce “generic” insulin products after they receive the proper regulatory approval.
Unfortunately, the regulatory process for “generic” insulins is not clearly defined at this point. Insulin, unlike many other pharmaceutical products, is a “biologic.” What this means is that it cannot be synthesized chemically – instead it’s produced through biological processes (for example, Lantus uses a strain of bacteria which makes the insulin). With chemically synthesized drugs, it is relatively easy for companies to demonstrate that their generic drug candidates are “bioequivalents” – they have the exact same active substances, doses, routes of administration, availability, and identical safety and efficacy profiles to the original reference drugs. However, biologics can never be considered truly equivalent to the original reference compounds. This is because biologics can be quite sensitive to changes in manufacturing processes (for example, changes in cell lines used, changes in purification techniques, etc.). As a result, the FDA does not currently have clear guidelines for the approval of “generic” biologics, or, in scientific jargon, “biosimilars.” The FDA is well aware of this issue, and is holding a meeting on November 2nd and 3rd to discuss requirements for regulatory approval of biosimilars.
Earlier this month, Pfizer obtained worldwide rights from the Indian pharmaceutical company Biocon to commercialize products in Biocon’s biosimilar insulin portfolio, including their version of Lantus (currently branded as Basalog in non-US markets, and produced using yeast in contrast to bacteria), and their (early) versions of Novolog and Humalog. As we understand it, Pfizer and Biocon will seek approval for their biosimilar insulins in the US and Europe as soon as patents expire.
Since a regulatory pathway for biosimilars has not yet been established in the US, Biocon intends to proceed with a ‘hybrid’ approach that contains elements of a typical New Drug Application, (NDA) and an application for a generic drug. How long it will take is not yet known. --VW/ST
We recently had the opportunity to watch a compelling documentary titled The Science of Inspiration, which chronicles the journeys of the twelve members of the inaugural Triabetes (the world’s largest triathlon club for people with diabetes) team in their quest to finish the 2008 Ironman Wisconsin triathlon – a grueling 2.4-mile swim, 112-mile bike, and 26.2-mile run. Their mission and their motivation: to prove that there are no boundaries for people with diabetes – a critical message they wanted to spread, especially to children with diabetes. One participant proclaimed, “I have type 1, but it doesn’t have me.” Another said, “We’re not pro athletes, we’re Joe Diabetic,” encouraging all viewers that they can achieve anything – that there are no limits, even with diabetes. Participants highlighted how Triabetes changed their lives by connecting them with other members of the diabetes community, and by helping them to improve their health. While training, Dave Shack, a self-proclaimed “couch potato” from Boone, North Carolina, said that prior to joining Triabetes, there was a period in his life in which he didn’t even check his blood glucose regularly. Throughout the experience, Triabuddies (kids with diabetes) accompanied the participants for motivation, encouragement, and support, eventually crossing the finish line on the race day with their counterparts. At the end of The Science of Inspiration, Triabuddy Taylor Burger declared in a way that we believe will resonate with and inspire all with diabetes, “I am a person with diabetes, and I can overcome anything.”
The Triabetes legacy continues, with past participants having completed the Ironman Arizona in 2009, and current participants from across the nation training for the Ironman St. George set to take place in 2011 in Utah. To follow their progress, you can visit their Facebook or YouTube pages.
If you feel inspired, there are many ways you can get involved! Children can sign up to become Triabuddies for future triathlons, while adults can join the Triabetes team. For those of you looking to ease your way in, Insulindependence, Triabetes’ parent organization, offers a variety of other local clubs and programs, including walks, runs, surfs, dives, and various other outdoor adventures (see their website). If you’re interested in watching the documentary, stay tuned – we hope to provide you with screening dates and locations as they become available. --VW
Every year on November 14, we pay homage to everyone living with or caring for someone with diabetes through the World Diabetes Day Monument Challenge, when landmarks around the globe are illuminated in blue, the color of the International Diabetes Federation’s (IDF) diabetes symbol. Here in San Francisco, the diaTribe team plans to celebrate under the blue glow of the Metreon shopping center, in the heart of downtown San Francisco. Last year, over 1,000 monuments were lit up worldwide, from village hospitals in India to City Halls in the United States. We look forward to this event every year –gathering with family, friends, and colleagues, to support diabetes awareness; we are reminded of how strong the diabetes community can really be.
Every year, the World Diabetes Day campaign highlights a specific theme. This is the second year of a five-year campaign (2009-2014) to address Diabetes Education and Prevention. The date, November 14, marks the birthday of Frederick Banting, who was instrumental in the discovery of insulin in 1922. We invite anyone in the Bay Area to swing by San Francisco and join us in celebrating World Diabetes Day on the evening of Sunday, November 14. And for those of you who can’t make it to the San Francisco Bay Area, we encourage you to celebrate by lighting your own house or office building blue or even approaching a government official about doing so with one of your town’s own local landmarks. For more up-to-date information on our whereabouts and plans for World Diabetes Day, follow us on twitter here. --ST