Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis

Robert Spiera, Masataka Kuwana, Dinesh Khanna, Laura Hummers, Tracy M. Frech, Wendy Stevens, Marco Matucci-Cerinic, Suzanne Kafaja, Oliver Distler, Jae Bum Jun, Yair Levy, Piotr Leszcyzński, Jessica Gordon, Virginia Steen, Eun Bong Lee, Tomasz Jankowski, Irena Litinsky, Lorina Chung, Vivien Hsu, Maureen MayesNora Sandorfi, Robert W. Simms, Stephanie Finzel, Jeska de Vries-Bouwstra, Scott Constantine, Nancy Dgetluck, Quinn Dinh, Bradley J. Bloom, Daniel E. Furst, Barbara White, Christopher P. Denton

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: This phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a cannabinoid type 2 receptor agonist, in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods: A multinational double-blind study was conducted in 365 dcSSc patients who were randomized and dosed 1:1:1 with lenabasum 20 mg, lenabasum 5 mg, or placebo, each twice daily and added to background treatments, including immunosuppressive therapies (IST). Results: The primary end point, the American College of Rheumatology combined response index in dcSSc (CRISS) at week 52 for lenabasum 20 mg twice a day versus placebo, was not met, with CRISS score of 0.888 versus 0.887 (P = 0.4972, using mixed models repeated measures [MMRM]). The change in the modified Rodnan skin thickness score (MRSS) at week 52 for lenabasum 20 mg twice a day versus placebo was −6.7 versus −8.1 (P = 0.1183, using MMRM). Prespecified analyses showed higher CRISS scores, greater improvement in MRSS, and lower decline in forced vital capacity in patients on background mycophenolate and those who were taking IST for ≤1 year. No deaths or excess in serious or severe adverse events related to lenabasum were observed. Conclusion: A benefit of lenabasum in dcSSc was not demonstrated. Most patients were treated with background IST, and treatment with mycophenolate mofetil in particular was associated with better outcomes. These findings support the use of IST in the treatment of dcSSc and highlight the challenge of demonstrating a treatment effect when investigational treatment is added to standard of care IST. These findings have relevance to trial design in SSc, as well as to clinical care.

Original languageEnglish (US)
Pages (from-to)1608-1618
Number of pages11
JournalArthritis and Rheumatology
Volume75
Issue number9
DOIs
StatePublished - Sep 2023

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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