The FDA decision will delay the drug’s possible launch by at least two years, according to company officials.
Takeda Global Research & Development Center partnered with PPD to develop alogliptin, a selective dipeptidyl peptidase IV (DPP-4) inhibitor under investigation for the treatment of Type 2 diabetes as an adjunct to diet and exercise.
PPD announced on March 6 that the FDA had informed Takeda that, although the alogliptin NDA was filed prior to the release of the December 2008 FDA guidance titled, “Guidance for Industry: Diabetes Mellitus — Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes,” the FDA did not believe that the amount of existing alogliptin clinical data was sufficient to meet certain statistical requirements outlined in that guidance. The FDA has asked Takeda to conduct an additional cardiovascular safety trial that satisfies the December 2008 FDA guidance.
In recent months, the FDA and Takeda have been in discussions about conducting an additional cardiovascular study for alogliptin.
Takeda received a “complete-response” letter on Friday, and the letter, according to a company press release, stated that existing clinical data were insufficient to meet the new cardiovascular safety requirements requested by the FDA.
The decision regarding alogliptin was expected, given that the FDA issued a guidance document in December 2008 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. Although the new drug application for alogliptin was filed in 2007, the new cardiovascular safety hurdle applied to all diabetes drugs, even those in development.
The recommendation emerged after concerns were raised about the cardiovascular safety of drugs in this field, especially the thiazolidinediones, including rosiglitazone (Avandia, GlaxoSmithKline). Takeda was informed in March that the available safety data were insufficient for approval and is currently in discussions with the FDA about the protocol for a new study.