Corbus CRB-913 Delivers 5% Weight Loss in Phase 1b Obesity Study

Corbus Pharmaceuticals NASDAQ: CRBP reported top-line results from CANYON-1, a Phase 1b trial evaluating CRB-913, an oral, peripherally restricted CB1 inverse agonist for obesity. The 12-week, placebo-controlled study enrolled 254 patients across 15 U.S. sites, with participants having an average body mass index of approximately 37 and 71% of participants being female.

Chief Executive Officer Yuval Cohen said the trial was designed to assess whether a CB1 inverse agonist could produce weight loss while limiting the psychiatric safety concerns associated with earlier, brain-penetrant drugs in the class. According to Cohen, CRB-913 was engineered to minimize brain exposure, with approximately 2% of the brain penetration of rimonabant and 15 times less brain penetration than Novo Nordisk's discontinued CB1 inverse agonist monlunabant.

At the highest tested dose of 60 milligrams once daily, CRB-913 achieved an average 5% placebo-adjusted weight loss at 12 weeks, according to the company. Cohen said all participants who completed treatment in the 60-milligram cohort lost weight, and the study showed no evidence of a weight-loss plateau over the 12-week period.

The trial evaluated three dose levels and placebo. Cohen said all three active doses achieved statistically significant weight loss compared with placebo, with separation between dose groups becoming more apparent as participants were titrated to higher doses. The highest individual weight loss reported in the 60-milligram group was slightly more than 13%, although Cohen characterized that result as an outlier.

Corbus compared its early results with published data for oral GLP-1 therapies, while cautioning that such cross-trial comparisons have limitations. Cohen said CRB-913's 12-week weight-loss profile appeared to be in line with oral GLP-1 therapies, while emphasizing that CRB-913 works through a distinct mechanism and is not an incretin-based drug.

The company highlighted psychiatric and gastrointestinal tolerability as central considerations for the program. Earlier CB1 inverse agonists, including rimonabant, faced concerns involving depression and suicidality. Cohen said CANYON-1 recorded no suicidality and no serious treatment-related adverse events across dose cohorts. All reported psychiatric adverse events were mild or moderate, transient and resolved, according to the company.

The 60-milligram group had one moderate case of depressive symptoms. Anxiety and insomnia rates were described as low and not notably different from placebo, while irritability occurred only in active-treatment participants and was mild. Cohen said the company used a more stringent PHQ-9 psychiatric screening threshold than is typical in obesity studies. In response to an analyst question about the applicability of the data to a broader population, he said roughly 4% of screened patients failed the PHQ-9 criterion, suggesting the enrolled study population was not materially different in that regard from a general U.S. obesity population.

On gastrointestinal events, Cohen said the company observed less vomiting and constipation, as well as a lower nausea rate, than reported in published studies of oral semaglutide and orforglipron. Diarrhea appeared to be at similar or slightly higher levels, he said. All gastrointestinal adverse events in CANYON-1 were mild or moderate, with no severe or serious gastrointestinal events reported. Treatment discontinuations for any reason averaged about 20%, a rate Cohen said was broadly typical for obesity studies and similar to placeb...