Documents released ahead of a US regulatory panel meeting on Tuesday suggest the chances of Orexigen Therapeutic's Contrave becoming the first weight loss drug to be approved in the USA in over a decade are not so good.
Papers have been published on the website of the US Food and Drug Administration ahead of a meeting of its Endocrinologic & Metabolic Drugs Advisory Committee on December 7 which will evaluate Contrave (sustained-release naltrexone/bupropion), which is partnered with Japan's Takeda. Orexigen hopes the combo will be approved for the treatment of obesity and weight management.
The FDA staffers noted that patients treated with Contrave in clinical trials lost 4.2% more of their weight than those on placebo after a 56 weeks, below the agency's recommended benefit of 5%. Still, they noted that about twice as many patients on the combo lost at least 5% more of their weight than those on placebo, thereby meeting FDA guidelines.
However the staffers were concerned that Contrave may cause a small but statistically significant increase in blood pressure and heart rate. They said the drug “attenuates or eliminates the blood pressure and pulse reduction that are normally seen with weight loss" and "it is not known how these vital sign changes in the overweight and obese population would impact cardiovascular risk over the long-term".
The reviewers suggest a dedicated study would be needed to assess Contrave's cardiovascular and the EMDAC will vote on whether it should be conducted before or after approval. The former option would prevent the drug hitting the market for many years.
Contrave is the last of drugs in this indication to be assessed by the FDA this year. Arena Pharmaceuticals/Eisai's lorcaserin and Vivus' Qnexa (phentermine/topiramate) have failed to make the grade and no new weight loss drug has been approved by the FDA since Roche's Xenical (orlistat) in 1999. In October, the FDA called on Abbott Laboratories to suspend sales of its controversial obesity drug Meridia (sibutramine) over cardiovascular safety fears.