Orexigen Therapeutics, a biopharmaceutical company focussed on the treatment of obesity, announced that Orexigen and North American partner Takeda Pharmaceuticals have received notification of a Paragraph IV certification for certain patents for Contrave (naltrexone HCl and bupropion HCl extended release) which are listed in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, or the Orange Book.
The certification resulted from the filing by Actavis Laboratories FL of an Abbreviated New Drug Application (ANDA) challenging such patents for Contrave.
Orexigen and Takeda plan to vigorously enforce Contrave intellectual property rights.
In accordance with the Hatch-Waxman Act, Takeda and Orexigen have 45 days after effective notice of the Paragraph IV certification to file suit against the ANDA filer in order to obtain an automatic stay of FDA approval of the ANDA until the earlier of 30 months from Takeda's receipt of the notice or a district court decision finding that the identified patents are invalid, unenforceable or not infringed.
Contrave, approved by the United States Food and Drug Administration 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 exact 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. Nonclinical studies suggest that naltrexone and bupropion have effects on two separate areas of the brain involved in the regulation of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system).
Four 56-week multicenter, double-blind, placebo-controlled phase 3 clinical trials were conducted to evaluate the effect of Contrave in conjunction with lifestyle modification in 4,536 subjects randomised to Contrave or placebo. In these studies, the most common adverse reactions (=5 percent) seen in patients taking Contrave included nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.