new now next

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

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