The FDA has sent a complete response letter, rejecting Orexigen Therapeutics and Takeda Pharmaceutical Company Limited’s new drug application for Contrave (naltrexone HCl/bupropion HCl) extended-release tablets for the treatment of obesity, including weight loss and maintenance of weight loss.
The agency expressed concern about the cardiovascular safety profile of naltrexone/bupropion when used long-term in a population of overweight and obese subjects.
Specifically, the letter stated that "before your application can be approved, you must conduct a randomized, double-blind, placebo-controlled trial of sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese subjects treated with naltrexone/bupropion does not adversely affect the drug's benefit-risk profile."
"We are surprised and extremely disappointed with the agency's request in light of the extensive discussion and resulting vote on this topic at the Dec. 7 Advisory Committee meeting," said Michael Narachi, president and CEO of Orexigen. "We plan to work closely with the agency to gain more information to determine the appropriate next steps regarding the Contrave application."
This rejection may be indicative a greater concern within the FDA over the potential for adverse cardiovascular risks with these types of drugs, which led to the rejection of Vivus' Qnexa and the removal of Abbott's Meridia off the U.S. shelves.
Contrave, an investigational combination therapy of naltrexone HCl and bupropion HCl, was studied for its ability to help people with obesity initiate and sustain weight loss, according to the companies. Contrave was submitted for U.S. regulatory approval in March 2010. The original submission was based on clinical trials that evaluated Contrave in more than 4,500 patients.