Contrave from Orexigen Therapeutics and partner Takeda Pharmaceutical was denied approval over its potential heart risks. Had it been approved, it would be the first new prescription diet pill in more than 10 years.
The drug now joins Arena Pharmaceuticals' lorcaserin and Vivus' Qnexa – which were both turned down in October. But unlike the other two, Contrave was endorsed by a panel of expert advisers in December.
This prompted Forbes’ The Medicine Show to write: “the field of obesity drugs is effectively dead... The clear lesson is that weight-loss medicines simply do not have enough of a benefit to justify any risk – and that this makes getting them approved just about impossible."
Contrave tablets are supposed to boost metabolism while curbing appetite and cravings – by combining the anti-addiction drug naltrexone with antidepressant bupropion. It was submitted for regulatory approval in March 2010 based on multiple clinical trials involving more than 4500 people.
About 35% of those patients with obesity lost at least 5% of their starting weight within one year, but they also experienced increased blood pressure and pulse rates [Reuters].
"We are surprised and extremely disappointed…" says Orexigen president and CEO, Michael Narachi, who wishes to work with the FDA on “next steps.”
These next steps include a large clinical study on its cardiovascular risks. The letter from the FDA specified: “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."
This could take up to 6 years and $200 million.
Obesity is widespread and a risk factor for many serious health issues, but the FDA has shown a high bar for drugs that would be taken indefinitely by millions of patients, many of whom don't have any current health problems.
Past failures – including the fen-phen combination that led to heart-valve problems in some patients – serve as a reminder that safety is the primary concern at the agency.
Abbott Laboratories removed its weight-loss drug Meridia from the market last year under FDA pressure, with the agency saying the "very modest weight loss" from taking Meridia didn't justify its cardiovascular risk.
Shares of Orexigen traded down 71% to $2.62 from Monday's close of $9.09, and the move has erased more than $300 million in market value from the stock.
Image: pills by e-MagineArt.com via Flickr