CardioExchange Archive

Contrave, the investigational diet pill combination of naltrexone and bupropion, has been granted a possible new lease on life by the FDA. In January of this year, the FDA issued a complete response letter to Orexigen, the drug’s sponsor. Now Orexigen says that it has received guidance from the FDA that could lead to approval of the drug in 2014.

The FDA has “identified a very clear and feasible path forward for this important therapy,” said the company president and CEO.

To gain approval, Orexigen will have to perform a cardiovascular outcomes trial. The trial will enroll less than 10,000 patients and could lead to conditional approval after about 2 years, the company said. At the interim analysis, which would take place after about 87 events had occurred, the trial would have to rule out a hazard ratio of 2.0  At trial completion, it would need to rule out a hazard ratio of 1.4. The company said it hoped to initiate such a trial in the first half of 2012 after discussions with the FDA.

Writing in Forbes, Matt Herper pointed out that even if the trial is successful, approval is far from guaranteed:

The FDA told Orexigen, in writing, that “if the interim analysis meets the specified criteria to exclude an unacceptable increased cardiovascular (CV) risk, the drug could be approved.” That “could” is pretty important — the FDA might consider the results of such a trial and decide that Orexigen’s risks still don’t outweigh its benefits.

Sanjay Kaul, who was a member of the Contrave advisory panel, sent this comment:

It is heartening to hear the FDA is moving in the right direction with regards to establishing a regulatory standard for approval of obesity drugs that is modeled after the diabetes guidance. Greater clarity in outlining the metrics for a favorable benefit-risk assessment, including weight loss, improvement in cardiometabolic profile, and ruling out unacceptable cardiovascular risk a priori would help reduce the regulatory ambiguity. This is a good development for sorely needed therapeutics in this arena.

In a separate development, last week Vivus said that the FDA would allow it to resubmit its NDA for topiramate (Qnexa), another diet drug placed in limbo by the FDA, possibly leading to an FDA decision in 2012. Because of concerns about birth defects in women taking the drug, Vivus said it would seek an initial indication that would exclude women of child-bearing age.

A third diet drug, lorcaserin, has also been delayed, in this case due to findings of cancer in animals. In August Arena Pharmaceuticals said that it planned to resubmit its application by the end of the year.