Corbus' Oral CB1 Inverse Agonist CRB-913 Delivers 5% Weight Loss at 12 Weeks in Phase 1b CANYON-1 Trial
核心洞察
Corbus Pharmaceuticals reported positive topline CANYON-1 Phase 1b data showing CRB-913 produced statistically significant weight loss at all three tested doses in non-diabetic obese adults.
The 60 mg dose achieved 5.0% mean weight loss from baseline at 12 weeks, with no evidence of plateauing at any dose level.
CRB-913, a peripherally restricted CB1 inverse agonist, showed psychiatric adverse events broadly in line with GLP-1 drugs and no serious or severe psychiatric events.
Corbus Pharmaceuticals Holdings, Inc. (搜索) (NASDAQ: CRBP) reported positive topline data from the CANYON-1 Phase 1b trial of CRB-913, an orally delivered, highly peripherally restricted CB1 inverse agonist, in adults with obesity (搜索). The 60 mg dose produced a mean weight loss of 5.0% from baseline at 12 weeks, with statistically significant and clinically meaningful weight loss observed at all three dose levels and no evidence of plateauing at any dose.
The company said the data support CRB-913's potential to establish a new class of oral, non-incretin obesity (搜索) medicines. The results have been selected for a late-breaking presentation at ObesityWeek 2026, scheduled for November 14–17, 2026.
Trial Design and Patient Population
CANYON-1 was a 16-week double-blind, placebo-controlled, dose-ranging study that enrolled 254 obese, non-diabetic adult participants at 15 investigational sites in the United States (NCT07310901). Participants were randomized 1:1:1:1 to CRB-913 20 mg, 40 mg, or 60 mg dosed orally once daily, or placebo.
A dose titration regimen was used, with all participants receiving CRB-913 commencing at 20 mg/day and titrating up every two weeks to either 40 mg/day or 60 mg/day depending on their assigned cohort. Participants were dosed for 12 weeks and followed for an additional 4 weeks.
Efficacy Results
Weight loss was rapid and statistically significant across all dose cohorts. Least-squares (LS) mean percent change in weight from baseline at week 12 was 2.8% for the 20 mg cohort (n=65), 3.3% for 40 mg (n=61), and 5.0% for 60 mg (n=62), versus 0.0% for placebo (n=66). Placebo-adjusted LS mean weight loss was 2.8%, 3.3%, and 5.0%, respectively, with p-values versus placebo of <0.0001 for all three doses.
The efficacy estimand used a Mixed Model for Repeated Measures (MMRM) with percent change from baseline as the dependent variable; sex, treatment group, visit, and treatment group-by-visit interaction as categorical fixed effects; and baseline weight as a covariate, with an unstructured covariate matrix.
Weight loss response rates were significantly higher across all three CRB-913 cohorts compared with placebo. Among participants who completed the study and received the 60 mg dose, all lost weight, with 44.4% losing at least 5.0% from baseline and 6.7% losing more than 7.5%. The highest recorded weight loss in that cohort was 13.4% from baseline.
Safety and Tolerability Profile
CRB-913 was generally safe and well tolerated. Treatment discontinuations due to adverse events with CRB-913 ranged from 3.1% to 13.1%, in line with rates recorded for approved oral GLP-1s (6.9%–20.7%) and markedly lower than the 13%–42% study discontinuation rate reported with monlunabant.
Treatment-emergent psychiatric adverse events of special interest were infrequent, mild to moderate, and transient. No serious or severe psychiatric adverse events were reported. There were no cases of suicidality and only one case of transient moderate depressive symptom among a total of 188 participants dosed with CRB-913. Psychiatric adverse events were noted across all cohorts, including placebo, and generally showed no dose-related patterns. The most common psychiatric adverse event was irritability, and all cases were mild.
The company reported that psychiatric adverse events were broadly in line with those reported in clinical studies of liraglutide, semaglutide, and tirzepatide, and lower than those seen with monlunabant, a recently studied but subsequently discontinued CB1 inverse agonist with significantly higher brain penetration than CRB-913. In the CANYON-1 psychiatric adverse event table, depression was reported in 0% of the 20 mg and 40 mg cohorts and 1.6% of the 60 mg cohort, versus 0% for placebo; anxiety in 3.1%, 8.2%, and 4.8% versus 4.5% for placebo; irritability in 6.2%, 8.2%, and 9.7% versus 0% for placebo; and insomnia in 1.5%, 4.9%, and 0% versus 3.0% for placebo. Published data cited for liraglutide, semaglutide, and tirzepatide showed depression rates of 2%–4.6%, anxiety of 1.9%–7.2%, and insomnia of 2.9%–3.9%, while monlunabant Phase 2 data (n=180) showed depression in 3%–8%, anxiety in 10%–27%, irritability in 10%–17%, and insomnia in 7%–17%.
Gastrointestinal adverse events were mild or moderate across all CRB-913 doses, with no serious or severe cases reported, and were generally not dose-dependent. The emerging GI profile appears more tolerable than the oral GLP-1 class, with markedly less vomiting, constipation, and nausea. In the CANYON-1 GI adverse event table, vomiting occurred in 4.6% of the 20 mg cohort, 8.2% of the 40 mg cohort, and 1.6% of the 60 mg cohort, compared with 31% for oral semaglutide 25 mg and 14%–28% for orforglipron 36 mg. Nausea occurred in 15.4%, 26.2%, and 22.6% of CRB-913 cohorts versus 47% for oral semaglutide and 41%–48% for orforglipron; constipation in 4.6%, 1.6%, and 4.8% versus 20% and 24%–28%; and diarrhea in 21.5%, 26.2%, and 22.6% versus 18% and 3%–14%.
The company noted that these observations are cross-trial comparisons derived from separate clinical settings and do not represent head-to-head comparisons. Published safety data reflect adverse events reported over study durations longer than the 12-week CANYON-1 treatment period: 56 weeks for liraglutide, 68 weeks for semaglutide, 72 weeks for tirzepatide, 68 weeks for oral semaglutide 25 mg, and 36 weeks for orforglipron.
Investigator and Company Perspectives
"From a clinical practice perspective, a substantial number of patients with obesity (搜索) either cannot tolerate GLP-1 receptor agonists or do not achieve an adequate therapeutic response," said Harold Bays, M.D., Medical Director at Louisville Metabolic and Atherosclerosis Research Center/Monroe Biomedical Research, Clinical Associate Professor at the University of Louisville School of Medicine, and an investigator on the CANYON-1 trial. "In addition, more than 60% discontinue treatment within the first year. What I find particularly encouraging about the CANYON-1 study results is that weight reduction had not yet plateaued by the end of the 12-week treatment period, and that CRB-913 appears to have avoided the depressive effects associated with earlier central nervous system-acting cannabinoid receptor agonists."
Yuval Cohen, Ph.D., CEO of Corbus Pharmaceuticals, said, "We set out to test a key hypothesis: by successfully designing a peripherally restricted CB1 inverse agonist, can we deliver a safe and tolerable therapeutic alternative with competitive weight loss to oral GLP-1s? The CANYON-1 data provide an important confirmatory milestone of this hypothesis. We are excited about these results and look forward to the Phase 2 study of CRB-913."
Development Path
Corbus plans to engage with the FDA on the clinical development plan and expects to initiate a Phase 2 monotherapy study in the first half of 2027. The company is also evaluating the potential to combine CRB-913 with GLP-1 therapy.
Corbus Pharmaceuticals Holdings, Inc. (搜索) is a clinical-stage company focused on new therapies in oncology and obesity (搜索), headquartered in Norwood, Massachusetts. Its pipeline includes CRB-701, a next-generation antibody drug conjugate for the treatment of Nectin-4 (搜索)-expressing tumors, and CRB-913 for the treatment of obesity.