A Phase 3 trial to investigate lenabasum as a potential treatment for dermatomyositis, a rare and often fatal multisystem inflammatory autoimmune disease affecting muscle and skin, have been initiated by Corbus Pharmaceuticals.
The Phase 3 trial is called “DETERMINE” and is designed to evaluate the efficacy and safety of lenabasum for the treatment of dermatomyositis, a rare and serious multisystem inflammatory autoimmune disease that characteristically affects muscle and skin and can also involve the lungs, heart, joints, and gastrointestinal tract. The disease is characterized by significant morbidity, disability, and mortality despite the current standard-of-care treatment with corticosteroids or other immunosuppressive medications.
“We are delighted to have achieved many important regulatory and clinical milestones in the development of lenabasum this year, now including the initiation of this Phase 3 dermatomyositis study,” said Barbara White, M.D., Chief Medical Officer of Corbus. “The double-blinded placebo-controlled 1-year study is designed to include subjects with active muscle and/or skin disease who represent the clinical spectrum of dermatomyositis, making results applicable to the broad dermatomyositis population. If the efficacy data from this single Phase 3 study are positive and the safety profile continues to be favorable, we intend to approach regulatory authorities about a registration package for lenabasum for treatment of dermatomyositis.”
The DETERMINE Phase 3 study will test efficacy and safety of lenabasum in approximately 150 adults with dermatomyositis. Subjects will be randomized to receive lenabasum 20 mg twice per day, lenabasum 5 mg twice per day, or placebo twice per day in a 2:1:2 ratio. The primary efficacy outcome at Week 52 will be Total Improvement Score (TIS), which is a weighted composite measure of improvement from baseline in six endpoints, including Physician Global Assessment of Disease Activity, Physician Global Assessment of Extramuscular Disease Activity, Patient Global Assessment of Disease Activity, Health Assessment Questionnaire (patient-reported disability), Manual Muscle Testing, and muscle enzymes. Evaluation of key organ involvement – muscle, skin, and lungs, will be included in secondary efficacy outcomes. Change from Baseline in the Cutaneous Dermatomyositis Activity and Severity index (“CDASI”) activity score will be a secondary efficacy outcome.
“The start of DETERMINE represents an important milestone for Corbus and a major step forward towards our vision of becoming a leader in treating inflammatory and fibrotic diseases by targeting the endocannabinoid system with what we believe is one of the industry’s most innovative pipelines. This study is our third late-stage study in orphan chronic inflammatory diseases, that combined, address approximately 150,000 patients in the U.S. alone,” commented Yuval Cohen, Ph.D., CEO of Corbus.
Progression to Phase 3 testing is supported by data from a Phase 2 trial of lenabasum in subjects with refractory skin-predominant dermatomyositis. The safety and tolerability profile of lenabasum in dermatomyositis patients has been acceptable to date, with no serious or severe AEs related to lenabasum. All subjects who started the Phase 2 study completed the double-blind, placebo-controlled 16-week part of the study, and all subjects who started dosing in the open-label extension of the Phase 2 study completed 1-year of dosing. Lenabasum treatment was associated with an improvement of minus 9.4 points from baseline in the CDASI activity score, a validated outcome measure of skin disease severity, at the end of the 16-week double-blinded placebo-controlled portion of the study. At 12 months in the open-label extension, continued improvement in inflammatory skin involvement was observed in dermatomyositis subjects using a composite outcome, the CDASI activity score. The CDASI activity score improved from study start by a mean of -17.6 points at 12 months in the OLE. An improvement of -4 to -5 points in CDASI activity score is considered medically important, and 84% of subjects had improvement in CDASI activity score exceeding -10 points at 12 months in the OLE. Lenabasum treatment was associated with consistent improvement in other measures of skin disease activity, physician global assessment, patient global assessment, and patient-reported function and symptoms during the double-blinded placebo-controlled portion of the study. Multiple key efficacy outcomes further improved in the ongoing open-label extension Phase 2 trial.
Lenabasum has been granted Orphan Drug Designation for the treatment of dermatomyositis and Orphan Designation for the treatment of dermatomyositis from the EMA.
About Dermatomyositis
Dermatomyositis is a form of idiopathic inflammatory myositis. It is a chronic, rare systemic autoimmune disease affecting approximately 80,000 people in the US, EU and Japan. The disease is typically diagnosed in adults between 50 and 60 years old, although it can occur in children, and females are more commonly affected than males. Dermatomyositis is characterized by chronic inflammation, scarring or loss of cells in multiple organs, and damage to blood vessels. As with SSc, it is unknown why the body’s immune system becomes and stays activated, damaging the skin, muscles, and other organs in people with dermatomyositis.
