Safety and Efficacy of Lenabasum in a Phase II, Randomized, Placebo-Controlled Trial in Adults With Systemic Sclerosis

Objective To assess the safety and efficacy of lenabasum in diffuse cutaneous systemic sclerosis (dcSSc). Methods A randomized, double-blind, placebo-controlled, phaseIIstudy was conducted at 9SSc clinics in theUS. Adults with dcSSc of <= 6 years' duration who were receiving stable standard-of-care treatment were randomized to receive lenabasum (n = 27) or placebo (n = 15). Lenabasum doses were 5 mg once daily, 20 mg once daily, or 20 mg twice daily for 4 weeks, followed by 20 mg twice daily for 8 weeks. Safety and efficacy were assessed at weeks 4, 8, 12, and 16. Results Adverse events (AEs) occurred in 63% of the lenabasum group and 60% of the placebo group, with no seriousAEs related to lenabasum. Compared to placebo, lenabasum treatment was associated with greater improvement in the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score and other efficacy outcome measures that assessed overall disease, skin involvement, and patient-reported function. The medianCRISSscore increased in the lenabasum group during the study, reaching 0.33, versus 0.00 in the placebo group, at week 16 (P= 0.07 by 2-sided mixed-effects model repeated-measures analysis). Gene expression in inflammation and fibrosis pathways was reduced, and inflammation and fibrosis were improved on histologic evaluation of skin biopsy specimens, in the lenabasum group compared to the placebo group (allP <= 0.05). Conclusion Despite a short trial duration in a small number of patients in this phaseIIstudy in dcSSc, our findings indicate that lenabasum improves efficacy outcomes and underlying disease pathology with a favorable safety profile.