Shares in Orexigen Therapeutics have sunk over 35% after the firm suspended development of its obesity drug Contrave over what it regards as excessively high barriers to approval put in place by US regulators.
In February, the US Food and Drug Administration issued a complete response letter for Contrave (naltrexone/bupropion). The agency then requested that Orexigen conduct a trial of "sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese people treated with Contrave, which is partnered with Takeda, does not adversely affect the drug's benefit-risk profile.
The San Diego-based firm submitted a proposal which "explored approval for a narrowed indication in patients with lower cardiovascular risk until data from the proposed outcomes trial could be reviewed for label expansion". However, the FDA's Division of Metabolic and Endocrinologic Products (DMEP) says the latter "would not adequately address the approval deficiency and instead, requested a pre-approval cardiovascular outcomes trial".
Orexigen believes such a request is "unprecedented and would generate significantly more information than is necessary or feasible". The company has also been informed by the DMEP that it intends to hold a general advisory committee early next year to discuss cardiovascular assessment for obesity drugs. As such, "any agreement reached on the design of a cardiovascular outcomes trial would be subject to change".
Appeal against DMEP
Given the stance taken by the agency, Orexigen says it will appeal the DMEP's responses and is putting on hold any further clinical development for its obesity programmes in the USA "until a clear and feasible path to regulatory approval is identified". It will now "accelerate the exploration of opportunities for our product candidates" internationally.
Orexigen chief executive Michael Narachi said his team has been working "for the last several months with leading experts in the field of cardiovascular outcome trials" to develop a proposal that would "more than adequately address the question of theoretical CV risk". He added that "we remain very disappointed in the stance of the DMEP" and "we have serious concerns about the broader implications these actions may have on innovation in the obesity space".
The FDA has not approved any new weight loss drugs since Roche's Xenical (orlistat) in 1999 and it has also recently demanded additional data from two other potential obesity treatments - Arena Pharmaceuticals' lorcaserin (partnered with Eisai) and Vivus' Qnexa (phentermine/topiramate).