Orexigen’s Obesity Drug Contrave Meets FDA Benchmark

Orexigen Therapeutics, yesterday anounced that all three remaining trials in their Contrave Obesity Research Phase 3 Program succesfully meet critical FDA benchmarks and that it hopes to file a New Drug Application (NDA) with the US Food and Drug Administration (FDA) in the first half of 2010.

As blogged before, Contrave is a combination of bupropion SR/naltrexone SR for the treatment of obesity and food cravings.

Orexigen summarizes the key findings of the three trials as follows

– 48.0% and 56.3% of patients on Contrave32(1) in COR-I (NB-301) and COR-II (NB-303) lost at least 5% of their body weight after 56 weeks, approximately three times the placebo categorical response rates of 16.4% and 17.1%, respectively (ITT, p<0.001).

– Contrave patients in COR-I and COR-II on Contrave32 had mean weight loss of 6.1% and 6.4% after 56 weeks, compared to 1.3% and 1.2% on placebo, respectively (ITT, p<0.001).

– In the COR-Diabetes (NB-304) trial, 44.5% of patients on Contrave32 lost greater than or equal to 5% of their body weight after 56 weeks, more than double the 18.9% of patients on placebo (p<0.001). Contrave patients also showed a 0.6% reduction in HbA1c from baseline, compared to a 0.1% reduction in placebo. This difference of 0.5% is clinically and statistically significant (ITT, p<0.001).

– Key secondary endpoints met across the entire COR Phase 3 program included significant improvements in cardiovascular and metabolic risk factors such as waist circumference, visceral fat, HDL cholesterol and triglycerides.

– Additional analyses indicate that Contrave patients experienced reductions in the frequency and strength of food cravings and an increased ability to control their eating compared to placebo.

A full copy of the Orexigen press release with additioal information regarding trial desigs and outcomes is available here.

While Contrave is certainly not a new magic bullet for obesity, I can well imagine that this drug will be particularly helpful in obese patients stuggling with hedonic hyperphagia, addictive eating and mood disorders.

Given our limitations to effectively manage obesity by behavioural changes alone (leaving many patients with no alternative but to eventually get bariatric surgery), any safe and effective addition to the pharmacological armamentum for obesity is only too welcome.

Obviously, both buproprion and naltrexone have well-known side effects, and as with any medical treatment, a careful assessment of risk-benefit ratios will be required. Nevertheless, for patients who respond well and tolerate the combination of these compounds, Contrave, in addition to behavioural treatments, may well provide an important aid in weight management and preventing the many complications of obesity.

AMS
Berlin, Germany