Orexigen® ( )Therapeutics, Inc (Nasdaq: OREX) today announced new data from the COR-I, COR-II and COR-Diabetes trials for Contrave® (bupropion SR/ naltrexone SR) to expand on top-line results announced in July. Contrave is the first of the Company's two late stage candidates for the treatment of obesity. These data were presented during a panel discussion at the 27th Annual Scientific Meeting of The Obesity Society.
These new data show that after completing 56 weeks of therapy with Contrave32:
- Approximately 34-48% of patients lost at least 10% of their baseline body weight and approximately 17-23% lost at least 15%;
- Obese patients classified as higher risk for developing cardiovascular disease and diabetes demonstrated significant improvement in markers of cardiometabolic risk such as waist circumference, HDL, and triglycerides;
- Patients with type 2 diabetes taking Contrave who began the trial with a hemoglobin A1c (HbA1c) level greater than 8% saw a mean HbA1c reduction of 1.1%, which was highly statistically significant compared to placebo;
- Patients reported an increased ability to control their eating and resist food cravings; and
- There was no evidence of increased abuse liability.
"These data show that Contrave provides obese patients with meaningful reduction in weight and improvement in important markers of cardiometabolic risk, with even greater improvement seen in patients at higher risk," said Dennis Kim, M.D., Senior Vice President of Medical Affairs. "Results also illustrate the robust glycemic benefit of Contrave in patients who have poorly controlled diabetes, as defined by a hemoglobin A1C level greater than 8.0. These patients experienced a clinically meaningful A1C reduction of 1.1% from baseline."
Additional findings presented today from patients who completed 56-weeks of therapy include: Efficacy
Results ---------------- COR-I COR-II ----- ------ PBO Contrave32 PBO Contrave32>"The focus of today's panel discussion on pharmacotherapy among distinguished members of the scientific community serves as further validation that medication may play an important role in the treatment of obesity," said Eduardo Dunayevich, M.D., Chief Medical Officer, Orexigen Therapeutics. "We believe that, if approved, Contrave can benefit a broad range of obese patients. The results of the COR program, coupled with recently disclosed results from our Empatic Phase 2b trial, support our belief that these two product candidates can help fill the current gap in obesity treatment by providing physicians with multiple pharmacologic options to address the varying needs of this diverse patient population."
Contrave Obesity Research (COR) Trial Design and Safety Profile
All Phase 3 trials in the COR program were 56 week, randomized, double-blind, placebo-controlled trials. The co-primary endpoints were the proportion of patients achieving at least 5% weight loss and percent change in body weight compared to placebo. Secondary endpoints included multiple markers of cardiometabolic risk, patient reported food cravings and eating control measures, as well as HbA1c in the COR-Diabetes trial. Patients were randomized to receive either placebo or Contrave, BID, with a four week titration period.
As previously reported, seven serious adverse events were attributed by investigators as possibly related to Contrave treatment across the entire COR program. These include cholecystitis (gallbladder inflammation), seizure, palpitations, paresthesia and vertigo. The most frequently observed treatment-emergent adverse events were nausea, constipation and headache. Nausea was the leading adverse event resulting in discontinuation; however, for the majority of patients experiencing nausea, it was mild to moderate, transient and manageable.
At week 56, mean blood pressure was generally unchanged from baseline for Contrave patients compared to placebo patients, who tended to experience a slight decrease (approximately 2 mm Hg) from baseline. Contrave treatment did not appear to disrupt the normal circadian pattern of blood pressure. There was a slight increase in pulse (approximately 1 beat per minute) in Contrave patients compared to placebo patients, whose pulse was generally unchanged. There were no meaningful treatment effects on ECGs or laboratory measures including liver function tests. Treatment with Contrave was not associated with increases in symptoms of depression or suicidal ideation.
The Company is on track to submit a New Drug Application (NDA) for Contrave with the FDA in the first half of 2010.
Additional Presentations at The Obesity Society
Additional data including Intent-to-Treat (ITT) analyses from COR-I and COR-II will be presented as late-breaker presentations in the Marriott Ballroom Salon 2 on Tuesday, October 27, beginning at 11:00 am EST. In addition, three posters (220-P, 218-P, 216-P) featuring data from the COR-BMOD trial will be presented in the Marriott Exhibit Hall on Sunday, October 25 from 1-2 and 6:30-7:30 pm EST (posters available for viewing from 1-7:30pm).