Lenabasum Not Found to Be Effective in Diffuse Cutaneous Systemic Sclerosis

Lenabasum was not found to be effective in the treatment of diffuse cutaneous systemic sclerosis (dcSSc), according to study findings published in Arthritis & Rheumatology.

Lenabasum is a cannabinoid type 2-receptor agonist, which has been found to reduce fibrosis and inflammation in animal models.

A double-blind, placebo-controlled study (RESOLVE-1; ClinicalTrial.gov Identifier: NCT03398837) was conducted at 77 sites in North America, Europe, Asia-Pacific, and Israel between 2017 and 2020.

Patients with dcSSc and skin thickening proximal in the elbows, knees, or trunk were randomly assigned 1:1:1 to receive twice-daily 5 mg lenabasum, 20 mg lenabasum, or placebo for 52 weeks.

The primary outcome was the change in the American College of Rheumatology (ACR) Combines Response Index in dcSSc (CRISS) score.

The low- and high-dose lenabasum and control cohorts included 365 patients, with a mean age of 49.7, 49.7, and 51.9 years; 73.3%, 80.0%, and 74.0% were women; and 66.7%, 70.0%, and 71.5% were White, respectively.

At week 52, patients who received low-dose lenabasum had a median ACR CRISS score of 0.8270 (P =.3486) and those who received high-dose lenabasum had a score of 0.8880 (P =.4972), which did not significantly differ from the median score of those who received placebo (0.8870).

In the 5-mg lenabasum, 20-mg lenabasum, and placebo groups, respectively, changes in modified Rodnan Skin Score (mean difference [MD], -7.1 vs -6.7 vs -8.1; P =.1183), forced vital capacity (FVC) percent predicted (MD, -2.2% vs -1.6% vs -1.0%; both P ≥.516), Health Assessment Questionnaire-Disability Index (HAD-DI) scores (MD, -0.06 vs -0.13 vs -0.13; both P ≥.322), and Physician Global Assessment of Health related to dcSSc (MDGA) scores (MD, -1.9 vs -1.7 vs -1.8; both P ≥.516) differed significantly. However, patients who received 5 mg lenabasum reported a smaller change in Patient Global Assessment of Health (PtGA) related to dcSSc score compared with those who received placebo (MD, -0.3 vs -1.1; P =.015).

Any treatment-emergent adverse event was reported by 90.2% to 91.7% of lenabasum-recipients compared with 86.2% of placebo-recipients. The rates of serious (8.2%-9.2% vs 14.6%) and severe (3.3%-5.8% vs 13.0%) events were lower in the lenabasum compared with the placebo groups, respectively. One event in the high-dose lenabasum and 1 in the placebo group led to deaths due to myocarditis plus hypoxia and renal crisis plus acute respiratory failure, respectively. Both deaths were deemed as unrelated to the study.

The most common adverse events among patients who received 20 mg lenabasum were dizziness, diarrhea, nasopharyngitis, upper respiratory tract infection, nausea, headache, scleroderma-associated digital ulcer, and vomiting.

A major limitation of the study was that patients were able to continue using background immunosuppressive therapies, which may have contributed to the symptom improvement observed among placebo-recipients.

The study authors concluded, “The primary analysis of this study does not show efficacy for lenabasum in dcSSc. […] Results from the pre-specified subgroup analyses will require confirmation in additional studies to determine the potential of lenabasum for treating patients with dcSSc.”

Disclosures: This research was supported by Corbus Pharmaceuticals, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.