Corbus Pharmaceuticals announced topline results from the 52-week Phase 3 RESOLVE-1 study of lenabasum in patients with diffuse cutaneous systemic sclerosis (SSc). Topline data showed no significant differences in the primary and secondary endpoints when lenabasum was compared to placebo, both added to background drug therapy. Further analyses of data are underway, and results will be presented at upcoming medical conferences.
RESOLVE-1 was a 52-week, multinational, double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of lenabasum in 365 patients with diffuse cutaneous SSc. The patients received lenabasum at 20 mg twice daily, lenabasum at 5 mg twice daily, or placebo twice daily for 52 weeks. The majority of enrolled patients (84%) were receiving background immunosuppressive drugs.
For the primary endpoint, the median American College of Rheumatology Combined Response Index for Systemic Sclerosis (ACR CRISS) scores at Week 52 were 0.887 in the placebo arm and 0.888 in the lenabasum 20 mg twice daily arm. ACR CRISS is a composite endpoint that reflects the probability of patient improvement. The maximum achievable ACR CRISS score is 1.0. Lenabasum treatment was safe and well-tolerated in this study with no new safety signals observed.
Lenabasum was granted Orphan Drug designation and Fast Track designation for the treatment of SSc from the FDA and Orphan Designation for the treatment of SSc from the European Medicines Agency.
Additional studies evaluating lenabasum are currently underway, including a phase 3 study, DETERMINE, in dermatomyositis, a Phase 2 study in systemic lupus erythematosus, and a Phase 2b study in cystic fibrosis.
Lenabasum is a rationally designed, oral, small molecule that selectively binds as an agonist to the cannabinoid receptor type 2 (CB2), resolves inflammation, and limits fibrosis. CB2 is preferentially expressed on activated immune cells and on fibroblasts, muscle cells, and endothelial cells. In both animal and human studies conducted to date, lenabasum has induced the production of pro-resolving lipid mediators that activate endogenous pathways which resolve inflammation and speed bacterial clearance without immunosuppression. Data from animal models and human clinical studies suggest that lenabasum can reduce expression of genes and proteins involved in inflammation and fibrosis. Lenabasum has demonstrated promising activity in animal models of skin and lung inflammation and fibrosis in systemic sclerosis (SSc). Lenabasum is also active in animal models of lung infection and inflammation in cystic fibrosis and joint inflammation and scarring in rheumatoid arthritis.
About Systemic Sclerosis
Systemic sclerosis, a form of scleroderma, is a chronic, rare, debilitating autoimmune disease affecting approximately 200,000 people in the North America, EU and Japan. The disease affects effects the skin and internal organs and is driven by inflammation and fibrosis (scarring of tissue) which can lead to severe damage and failure of multiple organs including the skin, joints, tendons, gastrointestinal tract, lungs, heart, blood vessels and kidneys. There is no cure for systemic sclerosis, and current treatments address the clinical manifestations of the disease, not the underlying mechanisms that drive inflammation and fibrosis.