Amid disappointing sales, Takeda Pharmaceuticals U.S.A. has cancelled its collaboration agreement with Orexigen Therapeutics for the commercialization of Contrave (naltrexone/bupropion), an obesity treatment. Takeda announced that it would refocus its resources on drug launches in the antidepressant and inflammatory bowel disease markets.
The two companies agreed to a 180-day transition period, during which time Takeda will continue to commercialize Contrave in the United States before turning the drug over to Orexigen.
Contrave, approved by the FDA in September 2014, is indicated for use as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m2 or greater (obese), or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type-2 diabetes mellitus, or dyslipidemia).
The precise neurochemical effects of Contrave leading to weight loss are not fully understood. Contrave has two components: naltrexone, an opioid antagonist, and bupropion, a relatively weak inhibitor of the neuronal reuptake of dopamine and norepinephrine. Preclinical studies suggested that naltrexone and bupropion affect two separate areas of the brain involved in the regulation of food intake: the hypothalamus (the appetite regulatory center) and the mesolimbic dopamine circuit (the reward system).
Four 56-week, phase 3, double-blind, placebo-controlled trials compared Contrave and placebo, both administered in conjunction with lifestyle modification, in 4,536 subjects. The most common adverse events associated with Contrave included nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.
According to FiercePharmaMarketing, Takeda threatened to divorce Orexigen last year after the latter revealed early data from a cardiovascular outcomes trial, angering the FDA and leading to the study’s cancellation.
On the plus side (sort of), embattled drug maker Valeant has signed up with Orexigen to market Contrave in 19 countries in Europe under the trade name Mysimba.