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A potential non-immunosuppressive treatment option for patients with diffuse cutaneous systemic sclerosis.
In an open-label extension of a phase II study, lenabasum (a synthetic cannabinoid derivative) has shown acceptable safety and tolerability in diffuse cutaneous systemic sclerosis (dcSSc) with no severe or serious adverse events (AE). The results were presented at the Annual European Congress of Rheumatology (EULAR 2018) on June 13 in Amsterdam, The Netherlands.
“There is a critical unmet need for safe and effective therapeutics for patients with dcSSc,” said Professor Thomas DÃ¶rner, Chairperson of the Abstract Selection Committee, EULAR. “These results demonstrate a significant step forward in the clinical development of a potentially impactful treatment for people suffering with this devastating disease.”
Systemic sclerosis occurs in about 30 people per million population per year. The diffuse cutaneous subtype (dcSSc) is even rarer, affecting just one in every four patients with the disease. Only half of patients with dcSSc will survive for 10 years or more.
The treatments for dcSSc are very limited. Immunosuppressants are sometimes used, although there have been relatively few trials in dcSSc patients specifically because the disease is so rare and difficult to research.
“Our results are very encouraging and reinforce the positive findings from the double-blinded placebo-controlled part of the study with regard to safety and tolerability,” said Robert Spiera, MD, Director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, Weill Cornell Medical College in New York City and principal investigator. “We look forward to continuing our investigations to assess the role of lenebasum as a new treatment option for patients with dcSSC.”
Lenabasum (JBT-101) is a selective cannabinoid receptor type 2 agonist that activates resolution of innate immune response in humans and reduces inflammation and fibrosis in animal models of SSc. It is a synthetic, oral, non-immunosuppressive small molecule.
Phase II trial
The results of the initial phase II trial demonstrated that lenabasum had acceptable safety and tolerability in dcSSc and showed consistent evidence of clinical benefit. In addition, changes in gene expression were shown to be consistent with biologic effects of lenabasum on pathways relevant to SSc.
Thirty-six patients, who completed the phase II trial, enrolled into the 1-year open-label extension (OLE) to receive lenabasum 20 mg twice a day. Results suggested improvement in multiple efficacy outcomes measured both from the start of the original study and the OLE. In the 25 subjects who completed a year in the OLE, the mean improvements from the study start included an improvement in American College of Rheumatology Composite Response Index in dcSSc score by 56%. There was also a reduction in modified Rodnan Skin Score, Health Assessment Questionnaire Disability Index, Physician Global Assessment, and 5-D Itch Questionnaire by 8.6, 0.14, 0.9, and 2.3, respectively. Forced vital capacity percentage predicted was stable from the study start, with a mean change of 0.4%.
The mean duration of treatment in the OLE was 45 weeks, with 19 patients completing 60 weeks of treatment. Three subjects discontinued the trial, two because of AEs and one withdrew consent. AEs occurred in 33/36 subjects in the OLE; however, only seven had AEs related to lenabasum (none of which were severe). In total, one subject had an AE considered life-threatening, three severe, 21 moderate, and eight mild. One subject developed renal crisis involving two severe and one life-threatening/serious AE (deemed unrelated to lenabasum). The most common AEs across all subjects were upper respiratory tract infection (22%), urinary tract infection (14%), diarrhea (11%), skin ulcers (11%), and mild intermediate dizziness (8%).
Phase III trial underway
An international phase III clinical trial of lenabasum has been initiated with results expected in the first half of 2020.
For more information about other potential indications for lenabasum, please see Cannabinoid Derivative to Be Studied for Lupus Pain.
R. Spiera: None declared, L. Hummers: None declared, L. Chung: None declared, T. Frech: None declared, R. Domsic: None declared, V. Hsu: None declared, D. Furst: None declared, J. Gordon: None declared, M. Mayes Consultant for: Boehringer-Ingelheim, Mitsubishi-Tanabe, Astellas, Roche-Genentech, R. Simms: None declared, E. Lee Employee of: Corbus Pharmaceuticals, Inc., N. Dgetluck Employee of: Corbus Pharmaceuticals, Inc., S. Constantine Employee of: Corbus Pharmaceuticals, Inc., B. White Employee of: Corbus Pharmaceuticals, Inc.
Spiera R, Hummers L, Chung L, et al. Safety and efficacy of lenabasum (JBT-101) in diffuse cutaneous systemic sclerosis subjects treated for one year in an open-label extension of trial JBT101-SSC-001. Presented at: EULAR 2018; 13-16 June 2018; Amsterdam, The Netherlands. Abstact OP0006.