Takeda obesity drug rejected

The US Food and Drug Administration (FDA) has declined to approve the new drug application for Contrave (naltrexone/bupropion), the obesity drug being developed through a partnership between Takeda Pharmaceutical and Orexigen Therapeutics.

In a complete response letter (CRL) dated January 31, 2011, the FDA raised concerns about  Contrave's potential long-term cardiovascular risks in obese and overweight patients. The agency said the drug cannot be approved until the companies conduct a "randomised, 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."

Orexigen president and CEO Michael Narachi said the company will "work closely with the agency to gain more information to determine the appropriate next steps regarding the Contrave application."

The FDA's decision goes against the recommendation of its Endocrinologic and Metabolic Drugs Advisory Committee, which recommended at a meeting in December that the agency require a post-approval cardiovascular study of Contrave but determined that the current data is adequate for approval. The panel voted 13-to-7 that the data submitted in the companies' marketing application adequately demonstrate that the drug's risk-benefit profile is acceptable for long-term use in obese and overweight patients and 11-to-8 to recommend that the FDA require a post-approval study evaluating the risk for major adverse cardiac events.

The marketing application, which was submitted in March 2010, contains data from a  number of clinical trials that enrolled a total of more than 4,500 patients. The application seeks approval of the extended-release tablets for the treatment of obesity, including weight loss and maintenance of weight loss.

Contrave is a combination of naltrexone SR, a marketed drug used to treat alcohol and opioid addiction, and bupropion SR, a marketed drug that treats depression and aids in smoking cessation. The companies believe the two active ingredients in the experimental obesity drug work together to address both the biological and behavioural causes of obesity.

Takeda and Orexigen signed their partnership deal on the drug last year. The deal calls for Orexigen to lead pre-approval activities and Takeda to lead post-approval activities.