Background: Safe and effective treatments are of significant unmet need in DM. Lenabasum, a CB2 agonist that activates resolution of inflammation, improved skin disease, patient-reported outcomes, and biomarkers in a Phase 2 study of DM patients with active skin disease.

Objectives: To evaluate the efficacy and safety of lenabasum in a Phase 3 double-blind study in DM.

Methods: DM patients ≥ 18 years old with active skin with or without muscle involvement were enrolled in 55 sites in North America, Europe, and Asia-Pacific. Stable doses of background immunosuppressants were allowed. Subjects were randomized 2:1:2 to lenabasum 20 mg BID, lenabasum 5 mg BID, or placebo BID for 52 weeks, with visits ≤ 8 weeks apart. The study was stopped after all subjects completed Week 28. Some subjects had completed Week 52 by then. The primary efficacy endpoint was Total Improvement Score (TIS) at Week 28 and a secondary efficacy endpoint was TIS at Week 52, for lenabasum 20 mg BID vs placebo.

Results: 175 subjects (69 lenabasum 20 mg BID, 35 lenabasum 5 mg BID, 71 placebo BID) received study drug; 167 completed Week 28, and 103 completed Week 52. The most common reasons for study discontinuation were study stopped by Sponsor (34.3%), withdrawal of consent (4.5%), and adverse events (AEs, 3.9%), with similar rates among groups. Baseline demographics and disease measurements were similar among groups and in total subjects were (mean or %): age 52.0 years; 81.1% female, 75.4% White; MMT-8 133.3; CDASI activity score 23.4; HAQ-DI 0.84, MDGA 5.55, EMGA 5.23; and PtGA 5.12. Corticosteroids were used by 48.1% and 38.0%, immunoglobulins by 5.8% and 7.0%, and other immunosuppressives by 51.0% and 54.9%, and monoclonal antibodies by 8.7% and 7.0% of lenabasum and placebo groups at baseline, respectively. The primary efficacy endpoint was not met - mean (SD) TIS score was 28.3 (19.75) vs 27.2 (19.23) at Week 28 for lenabasum 20 mg BID vs placebo, p = 0.3311, MMRM. Week 52 values were 40.6 (16.88) vs 34.8 (19.94), p = 0.2290. When analyses were restricted to subjects with muscle weakness at baseline (MMT8 < 142), TIS scores and treatment differences were greater and reached nominal statistical significance at Week 40, p = 0.0172. Mean (SD) improvements in CDASI activity score were numerically greater but not statistically different between lenabasum 20 mg BID group vs placebo at Week 28 [-7.1 (7.76) vs -5.8 (8.88) points, p = 0.2775] and Week 52 [-10.0 (9.45) vs -6.2 (12.8) points, p = 0.0932]. When restricting analysis of participants without muscle weakness (MMT-8 = 150), improvement in CDASI activity score was greater in the lenabasum 20 mg BID group vs placebo at Week 28, p = 0.0461, and Week 52 p = 0.0059.

Treatment-emergent AEs (TEAEs) occurred in 87.0%, 85.7%, and 87.3% of lenabasum 20 mg BID, lenabasum 5 mg BID, and placebo groups, with no deaths. Related TEAEs leading to withdrawal of study product were infrequent, occurring in 1.4%, 0%, and 2.0% of subjects in the same groups. Serious TEAEs occurred in 11.6%, 8.6%, and 4.2% of subjects in the lenabasum 20 mg BID, lenabasum 5 mg BID, and placebo groups. No serious TEAE preferred term occurred in more than 1 subject in any group. TEAE occurring in ≥ 10% of lenabasum 20 mg BID subjects were (% lenabasum vs % placebo): dermatomyositis (flare) 27.5% vs 40.8%; diarrhea 14.5% vs 8.5%; dizziness 13.0% vs 4.2%; nausea 11.6% vs 4.2%; headache 10.1% vs 14.1%; and arthralgia 10.1% vs 2.8%.

Conclusion: Although, primary or secondary endpoints were not met in the study, subgroup analysis of patients with muscle weakness and without muscle weakness, showed improvement in muscle strength and rash, respectively in lenabasum 20 mg BID group vs placebo. Lenabasum was administered safely and was well-tolerated in this study.

Disclosure of Interests: Victoria Werth Speakers bureau: University of Pennsylvania, who own the copyright for the CLASI and SDASI, Consultant of: AbbVie, Amgen, Argenx, AstraZeneca, Biogen, BMS, Celgene, Chrysalis, CSL Behring, Cugene, Eli Lilly, EMD Serono, Genentech, GSK, Incyte, Idera, Janssen, Kirin, Medimmune, Medscape, Nektar, Octapharma, Pfizer, Principa, Regeneron, Resolve, and Viela Bio, Grant/research support from: AstraZeneca, Biogen, Celgene, Corbus Pharmaceuticals, Genentech, Gilead, Janssen, Pfizer, Syntimmune, and Viela Bio, Barbara White Shareholder of: Corbus Pharmaceuticals, Employee of: Previous employee of Corbus Pharmaceuticals, Nancy Dgetluck Shareholder of: Corbus Pharmaceuticals, Employee of: Corbus Pharmaceuticals, Kathleen Hally Shareholder of: Corbus Pharmaceuticals, Employee of: Corbus Pharmaceuticals, Scott Constantine Shareholder of: Corbus Pharmaceuticals, Employee of: Corbus Pharmaceuticals, Rohit Aggarwal Consultant of: For Abbvie, Q32, Alexion, AstraZeneca, BMS, Boehringer Ingelheim, Corbus, Csl Behring, EMD Serono, Galapagos, Janssen, Kezar, Jubliant, Kyverna, Mallinckrodt, Merck, Novartis, Octapharma, Pfizer, Octazyme, Roivant, Scipher., Grant/research support from: BMS, Mallinkrodt, EMD Serono, Q32, Pfizer, David Fiorentino Consultant of: Corbus Pharmaceuticals, Grant/research support from: Corbus Pharmaceuticals, Ingrid E. Lundberg Shareholder of: Roche and Novartis., Consultant of: Corbus Pharmaceuticals Inc, Astra Zeneca, Bristol Myer´s Squibb, Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, and Janssen, Grant/research support from: Astra Zeneca, Chester V Oddis Consultant of: Corbus Pharmaceuticals