BariatricSource

Orexigen® Therapeutics, Inc. today announced results from new intent to treat (ITT) analyses from the COR-I and COR-II Phase 3 trials of Contrave® (naltrexone SR/bupropion SR), the first of two late stage Orexigen candidates for the treatment of obesity. These data expand on top-line results announced in July and complement findings from a panel discussion on Saturday where the Company presented data on Contrave patients who completed 56 weeks of therapy. These ITT data were presented today in two late breaker oral presentations at the 27th Annual Scientific Meeting of The Obesity Society in Washington, D.C.

Results showed that, on an ITT basis,
-- Approximately 25-33% lost 10% or more of their body weight and 12-16%
lost at least 15%; and
-- Obese patients on Contrave demonstrated significant improvements in
important markers of cardiometabolic risk including waist
circumference, HDL and triglycerides

"The data presented today and on Saturday provide a deeper view of Contrave, and what we believe is a balanced efficacy and safety profile," said Eduardo Dunayevich, M.D., Chief Medical Officer of Orexigen. "These findings should help clinicians assess the potential value of Contrave pharmacotherapy in managing obesity and support our belief that if approved, Contrave could meet the broad range of needs of this patient population by virtue of its efficacy, safety and benefits on key markers of cardiometabolic risk."

Additional data from today's late breaker presentations are outlined in the below table:

 
  Efficacy Result(+)
                                  COR-I                       COR-II
  --------------------------------------------------------------------------
                             PBO      Contrave32         PBO      Contrave32
                           (N=511)     (N=471)         (N=456)     (N=702)
  --------------------------------------------------------------------------
  Greater than or equal
  to 10% weight loss (%)     7.4%       24.6%*           5.7%       32.9%*
  --------------------------------------------------------------------------
  Greater than or equal
  to 15% weight loss (%)     2.0%       11.9%*           2.4%       15.7%*
  --------------------------------------------------------------------------
  Markers of
  Cardiometabolic Risk(+)
  --------------------------------------------------------------------------
 
                                  COR-I                       COR-II
  --------------------------------------------------------------------------
                             PBO      Contrave32         PBO      Contrave32
                           (N=511)     (N=471)         (N=456)     (N=702)
  --------------------------------------------------------------------------
  Waist
  circumference (cm)         2.5        6.2*             2.1        6.7*
  --------------------------------------------------------------------------
  Fasting
  triglycerides (mg/dL)      3.5       18.1*             0.5       11.8*
  --------------------------------------------------------------------------
  Fasting HDL (mg/dL)        0.1       +3.4*             0.1       +3.6*
  --------------------------------------------------------------------------
  Fasting LDL (mg/dL)       -3.3       -4.4              2.1        6.2*
  --------------------------------------------------------------------------
  hsCRP (mg/L)              -0.4       -1.1*            +0.2       -0.8*
  --------------------------------------------------------------------------
 
  + Data based on intent-to-treat (ITT) last observation carried forward
    (LOCF) analyses of all randomized patients who had at least one
    post-baseline observation while on study drug.
  *p<.05 for difference between Contrave and placebo

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 measures of cardiometabolic risk, food cravings and eating control, 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, across the entire COR program, seven serious adverse events were attributed by investigators as possibly related to Contrave treatment. 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 and there was no evidence of abuse dependence.

The Company is on track to submit a New Drug Application (NDA) for Contrave with the FDA in the first half of 2010.

About Orexigen® Therapeutics
Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on developing therapies that offer multiple approaches to treating obesity. The Company's lead investigational product, Contrave®, has completed the COR clinical development program and is on track for a regulatory submission with the FDA in the first half of 2010. The Company's second obesity drug candidate, Empatic(TM) has completed Phase 2 trials. Each product candidate is designed to act on a specific group of neurons in the central nervous system with the goal of achieving appetite suppression and sustained weight loss, through combination therapeutic approaches.