Corbus Pharmaceuticals Holdings, Inc., a clinical stage drug development company targeting rare, chronic, serious inflammatory and fibrotic diseases, announced positive topline results from its 16-week Phase 2 study of safety and efficacy of anabasum in dermatomyositis (“DM”). The mean improvement (reduction) in the primary efficacy outcome, the Cutaneous Dermatomyositis Disease Area and Severity Index (“CDASI”) activity score, a validated outcome measure of skin disease severity, was 9.3 points for anabasum treatment at the end of the study versus a reduction of 3.7 points for placebo treatment (p = 0.04). Anabasum also outperformed placebo in multiple secondary efficacy outcomes studied. Anabasum was well tolerated with no severe or serious side effects associated with the drug. No subjects dropped out.
Study Design
The single center, double-blind, randomized, placebo-controlled trial enrolled 22 adult subjects in a 1 to 1 ratio of anabasum to placebo cohorts. At baseline, subjects in each cohort had a mean CDASI activity score in the severe range and skin symptoms in the extremely severe range despite background treatment with immunosuppressive drugs in 19 of the 22 subjects. Demographic parameters, CDASI activity scores, patient-reported outcomes, and use of immunosuppressive drugs at baseline were similar for anabasum and placebo cohorts. Subjects received anabasum 20 mg QD through week 4, then anabasum 20 mg BID through week 12 with safety and efficacy follow-up thereafter through week 16. All subjects remained on their background standard-of-care therapy throughout the study.
Primary Efficacy Endpoint
Improvement in CDASI activity scores in the anabasum cohort were ≥ 7.5 points and consistently superior to improvement in the placebo cohort from week 6 to end of study. The mean improvement (reduction) in CDASI activity score for the anabasum cohort (20 mg QD followed by 20 mg BID) from day 1 to end of study was 9.3 points versus 3.7 points for the placebo cohort (p = 0.04, 2-sided MMRM). The greater degree of improvement versus placebo in CDASI activity score occurred during dosing with anabasum 20 mg BID (treatment effect 6.3 points at end of study, p = 0.02, 2-sided MMRM). Improvement in CDASI activity score ≥ 4 points has been correlated with improvement in patient-reported quality of life outcomes, pain and physician global assessment.
Secondary Efficacy Endpoints and Safety Outcomes
Improvements across multiple secondary efficacy outcomes were seen in the anabasum cohort versus the placebo cohort, including statistically significant improvement in CDASI Damage Index (p = 0.04) and patient-reported symptoms and functioning. Anabasum was well tolerated and demonstrated a favorable safety profile with no serious or severe side effects related to the study drug and no study discontinuations.
Dr. Victoria Werth, MD, Chief, Dermatology, Philadelphia V.A. Hospital, Professor of Dermatology at the Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Center, Professor of Medicine, University of Pennsylvania and Principal Investigator in the Phase 2 study, stated, “I have extensive experience treating patients with DM and we currently have little to offer patients with moderate to severe disease activity except immunosuppressive therapies with often limited efficacy and significant side effects. My gratitude goes to the NIH for funding this first double-blind, randomized, placebo-controlled trial conducted in skin-predominant DM. The results signal a clear clinical benefit associated with anabasum with no evidence of immunosuppression. These positive data are even more striking given that the study was done in patients with high disease activity who remained on standard background immunosuppressive therapies during the study. Anabasum had minimal side effects and all patients completed the study, with nearly all of them volunteering for a long-term open label extension trial, which speaks to the excellent safety profile of anabasum and the need for effective treatments for DM.”
Barbara White, MD, Chief Medical Officer of Corbus, commented, “These results in this first-in-patient DM study in 22 subjects are exciting and demonstrate medically and statistically significant improvement in the primary endpoint in skin disease. Improvements in multiple secondary patient-reported outcomes, including a number that achieved statistical significance, reinforce the signal of activity of anabasum in DM. These data are consistent with our previously reported positive results from the completed Phase 2 systemic sclerosis trial — these two systemic autoimmune diseases share certain aspects of disease pathogenesis, signs and symptoms of disease, and even significant mortality. We look forward to discussion with regulatory authorities regarding the clinical development path forward.”
“These trial results mark the third time anabasum has demonstrated a clear signal of clinical benefit with a favorable safety profile in a rare, inflammatory disease, having done so recently in both systemic sclerosis and cystic fibrosis,” stated Yuval Cohen, PhD, CEO of Corbus. “We view these data as a strong validation of the unique mechanism of action of anabasum as the potential first non-immunosuppressive pro-resolving drug to target inflammation and fibrosis. Our focus now turns to successfully executing a clinical development plan aimed at bringing anabasum to the market as expeditiously as possible.”
The dermatomyositis trial was funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health to the University of Pennsylvania Perelman School of Medicine.
Filed Under: Drug Discovery
