Corbus’ Lenabasum No Better than Placebo in Late-Stage Study in Systemic Sclerosis

Corbus’ Lenabasum No Better than Placebo in Late-State Study

Rare Daily Staff

Corbus Pharmaceuticals said topline results from its late-stage study of lenabasum in patients with the rare and life-threatening autoimmune disease diffuse cutaneous systemic sclerosis showed no significant difference to placebo.

News of the results sent shares tumbling 75 percent to a low of $1.95 from a close of $9.25 in the previous trading session.

Systemic sclerosis, a form of scleroderma, is considered one of the most life-threatening rheumatic diseases. The disease affects the skin and internal organs and is driven by inflammation and 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.

Lenabasum is an oral, small molecule that selectively binds as an agonist to the cannabinoid receptor type 2, resolves inflammation, and limits fibrosis. CB2 is preferentially expressed on activated immune cells and on fibroblasts, muscle cells, and endothelial cells.

RESOLVE-1 is a 52-week, randomized, placebo-controlled phase 3 trial that tested the efficacy and safety of lenabasum in 365 patients with diffuse cutaneous SSc in a multinational, double-blind, randomized, placebo-controlled study, with dosing of 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 percent) were receiving background immunosuppressive drugs, reflecting recent trends in clinical practice. The study used the American College of Rheumatology Combined Response Index for Systemic Sclerosis (ACR CRISS) scores at Week 52 as the primary endpoint. The score in the placebo arm was a median of 0.887 compared to 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.

Similar proportions of placebo-treated and lenabasum-treated subjects had at least one treatment emergent adverse event (AEs), 86.2 percent in the placebo arm and 91.7 percent in the lenabasum 20 mg twice daily arm. Serious AEs occurred in 14.6 percent of subjects in the control arm and 9.2 percent of subjects in the lenabasum 20 mg twice daily arm. Severe AEs occurred in 13 percent of subjects in the control arm and 5.8 percent of subjects in the lenabasum 5 mg twice daily arm. No subjects receiving lenabasum withdrew from the study because of an AE-related to study drug.

Lenabasum treatment was well-tolerated in this study. No evidence of lenabasum-related immunosuppression or new safety signals for lenabasum were observed.

Further analyses of these data are underway, and once Corbus has a fuller understanding of the data, the company said it would like to engage with the FDA to determine potential next steps in this clinical development program. The data will be presented at upcoming medical conferences.

“I am genuinely surprised by these results. Immunosuppressive drugs, alone or in combination, are increasingly becoming a mainstay of treatment for patients with early diffuse cutaneous SSc,” said Robert Spiera, co-principal investigator on RESOLVE-1 and director of the Scleroderma, Vasculitis, and Myositis Program at the Hospital for Special Surgery, Weill Cornell Medical College in New York City. “However, the impact of these drugs on disease has not previously been studied systematically and clearly was underappreciated by the community of SSc experts. The high degree of efficacy of background drug therapy in the control arm is well beyond what was expected.”

Barbara White, chief medical officer and head of research at Corbus, said the company will conduct further analyses of the data to potentially identify groups of patients that may have responded to lenabasum.

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.

Lenabasum is currently being evaluated in a phase 3 DETERMINE study in dermatomyositis, a phase 2 study in systemic lupus erythematosus, and a phase 2b study in cystic fibrosis.

Photo: Robert Spiera, co-principal investigator on RESOLVE-1 and director of the Scleroderma, Vasculitis, and Myositis Program at the Hospital for Special Surgery, Weill Cornell Medical College in New York City