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S-1/A
OREXIGEN THERAPEUTICS, INC. filed this Form S-1/A on 02/16/2007
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We initiated clinical testing of Contrave with a Phase II clinical trial in 2004. This trial enrolled 238 patients at eight U.S. clinical trial sites to evaluate the safety and efficacy of the Contrave combination. The primary endpoint for this trial was percent change in body weight 16 weeks after the start of treatment, with secondary endpoints that included the percent change in body weight 24 weeks after the start of treatment. Results from this trial are summarized as follows:
 
  •      On an intent-to-treat basis, which includes all randomized patients who recorded at least one post-baseline body weight measurement, Contrave demonstrated mean weight loss of 4.0% of baseline body weight at 16 weeks and 5.2% at 24 weeks.
 
  •      On a completer basis, which includes patients who completed treatment through particular milestones, Contrave demonstrated mean weight loss of 4.8% of baseline body weight at 16 weeks and 6.8% at 24 weeks.
 
  •      Patients who received placebo in this trial showed mean weight loss of 1.0% at 16 weeks on both an intent-to-treat and completer basis. The placebo arm of the trial was discontinued at that point, as specified in the clinical trial protocol.
 
In July 2005, we proceeded to study Contrave in a larger Phase IIb trial exploring a higher dose of bupropion SR paired with three different doses of naltrexone IR. This trial enrolled 419 patients at eight U.S. clinical trial sites under placebo-controlled, double-blind conditions. The primary endpoint for this trial was percent change in body weight 24 weeks after the start of treatment. Results from this trial are summarized as follows:
 
  •      On an intent-to-treat basis, the three Contrave dosage groups demonstrated mean weight loss of 4.3% to 5.4% of baseline body weight at 24 weeks, compared to mean weight loss of 0.8% among the placebo group.
 
  •      On a completer basis, the three Contrave dosage groups demonstrated mean weight loss of 7.0% to 7.6% of baseline body weight at 24 weeks, compared to mean weight loss of 1.1% among the placebo group.
 
The protocol for this study permitted participants to continue on Contrave for an additional 24 weeks of open-label treatment. The study is ongoing and 48 week data are not yet available. Through 36 weeks:
 
  •      On an intent-to-treat basis, the three Contrave dosage groups demonstrated mean weight loss of 4.6% to 6.1% of baseline body weight.
 
  •      On a completer basis, the three Contrave dosage groups demonstrated mean weight loss of 8.0% to 9.3% of baseline body weight.
 
The most common side effects observed in our clinical trials of Contrave to date include nausea, dizziness, insomnia and headaches.
 
Excalia
 
Excalia is a fixed dose combination of zonisamide SR and bupropion SR. The combination of zonisamide and bupropion, in our screening model, produced an eight-fold increase in relevant neuronal activity, suggesting that this drug combination would enhance satiety and energy expenditure. Based on the strength of these results and Excalia’s unique mechanism of action, we selected this product combination to complement our Contrave clinical development program. We hold an exclusive license to an issued U.S. patent covering the Excalia composition, and we have filed additional patents covering various compositions, methods of use and formulations.
 
Zonisamide IR was approved in the United States in 2000 for the adjunctive treatment of partial seizures, which is a form of epilepsy. The precise mechanism of zonisamide is unknown; however, it is believed that zonisamide has a number of pharmacologic mechanisms including sodium-channel modulation and enhancement of dopamine and serotonin neurotransmission. Zonisamide, given alone, has also shown weight loss in prior clinical trials conducted at Duke University.


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