March 13, 2009 (Rockville, Maryland) — One of the first signs that the FDA will enforce its recommendations that companies intensively study the cardiovascular risk profile of diabetes drugs they're developing came last week with an announcement from the FDA that the cardiovascular safety data that it is in the process of reviewing for alogliptin (Takeda Pharmaceutical) are "insufficient."
A Takeda press release  notes that the company is "open to discussions regarding the design of additional CV studies with alogliptin." The announcement, however, is expected to delay approval of the drug and has led to a plunging of Takeda's share price.
In December 2008, the FDA issued a guidance document, based on Endocrinologic and Metabolic Drugs Advisory Committee recommendations, advising sponsors to conduct long-term clinical trials or provide equivalent evidence ruling out an unacceptable cardiovascular safety risk for new diabetes drugs seeking approval.
The announcement that alogliptin would be affected by the recommendations may come as a surprise to some, given that the new drug application (NDA) for the drug was filed back in 2007. "At least my understanding prior was that there would be a bit of 'grandfathering' for this guidance, with most assuming the line would be drawn at the point of NDA filing," Dr Darren McGuire (UT Southwestern, Dallas, TX), a recent appointee to the Cardiovascular and Renal Drugs Advisory Committee, told heartwire . "With lots of drugs in pretty advanced phases of testing, this provides a pretty clear directive from the FDA regarding application of the new CVD guidance, that all drugs henceforth will be judged accordingly."
Concerns over the cardiovascular safety of diabetes drugs, in particular rosiglitazone (Avandia, GlaxoSmithKline) and muraglitazar (Bristol-Myers Squibb), dominated cardiology news in 2007 and early 2008, compounded by the ACCORD trial results. Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is under review as an adjunct to diet and exercise for the treatment of type 2 diabetes, a Takeda press release notes.
Takeda Pharmaceutical. Takeda receives new information on alogliptin (SYR-322) NDA [press release]. March 6, 2009. Available at: https://www.takeda.com/press/article_32750.html.
Heartwire from Medscape © 2009 Medscape
Cite this: "Insufficient" Data: FDA Applies Tough New CV-Safety Requirements to Diabetes Drug Alogliptin - Medscape - Mar 13, 2009.