Orexigen Therapeutics' stock collapsed yesterday after US regulators turned away its weight loss drug Contrave, requesting a lengthy and expensive additional trial.
The US group's share price plummeted more than 72% as shareholders went into shock after the US Food and Drug Administration issued a complete response letter regarding its application to market Contrave (naltrexone HCl/bupropion HCl) for the treatment of obesity, including weight loss and the maintenance of weight loss.
Hopes for marketing approval - and thereby the first new weight loss pill in a decade - had been high given that, in December, the FDA's Endocrinologic & Metabolic Drugs Advisory Committee voted 13-7 that the benefits of the drug, which is partnered with Japan's Takeda, outweigh the risks in patients who need to loose weight.
The Committee agreed that concerns over a small but statistically significant increase in blood pressure and heart rate associated with Contrave could be addressed by a post marketing study, and argued that the medicine should be given a green light despite being dangerously close to the FDA's efficiency threshold for weight-loss drugs.
But in its rejection letter the FDA went against the recommendations instead taking the position that the long-term cardiovascular safety issue must be determined before Contrave can be released onto the market.
"Before your application can be approved, you must 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," the regulator told Orexigen.
Such a trial represents a significant delay to market approval and, of course, a significant amount of resources, and therefore represents a bitter blow for the firm. "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 December 7 Advisory Committee meeting," said Michael Narachi, Orexigen's president and chief executive. But he stressed the company plans to work closely with the regulator "to gain more information to determine the appropriate next steps regarding the Contrave application".
The FDA has not approved any new weight loss drugs since Roche's Xenical (orlistat) in 1999. Contrave's rejection marks a hat-trick of recently failed applications, following that of Arena’s lorcaserin and Vivus' Qnexa (phentermine/topiramate) in Autumn last year, for which the Agency is also seeking additional sets of data.