Updated results from the RESOLVE-1 Phase 3 clinical trial show that treatment with lenabasum reduces lung function decline in adults with diffuse cutaneous scleroderma (dcSSc) who are on long-term immunosuppressant therapy.
“We are encouraged by the post-hoc [subsequent] analyses pointing to lenabasum’s therapeutic potential,” Yuval Cohen, PhD, CEO of lenabasum’s developer Corbus Pharmaceuticals, said in a press release. “We believe these findings offer a rationale for additional clinical development of lenabasum, a non-immunosuppressive agent, that could address lung function decline in systemic sclerosis patients.”
Scleroderma is characterized by hardening, or sclerosis, of the skin tissue. In dcSSc, sclerosis is more widespread in skin tissue and may spread systemically to internal organs, including the lungs, heart and kidneys.
Lenabasum is an oral small molecule therapy that activates the cannabinoid receptor type 2 on the surface of immune cells and connective tissue cells called fibroblasts. Ultimately, the potential treatment is intended to instruct cells to turn off inflammatory responses, easing inflammation and fibrosis (scarring).
RESOLVE-1 (NCT03398837) is an international study that enrolled 365 adults with dcSSc, who were assigned randomly to receive twice-daily 5 or 20 mg doses of either lenabasum or a placebo for one year.
Recent top-line data from the trial showed that lenabasum failed to outperform the placebo at one year of treatment, when analyzing a composite measure of different aspects of treatment response. This finding was attributed to an unprecedented improvement in the placebo group, especially in participants in their first two years of background immunosuppressants.
The new data revealed that in patients who were on background immunosuppressant therapy for more than two years (38 patients), lenabasum was associated with a reduction in forced vital capacity (FVC) decline after one year of treatment compared to the placebo (26 participants). Notably, FVC refers to the amount of air a patient can forcibly exhale after taking a deep breath. It is an indicator of lung involvement and of lung function decline, and can be measured in milliliters or percent predicted.
In the same patient group, treatment with the 20 mg dose decreased the likelihood of patients declining in FVC, or worsening by more than 5% (19% with lenabasum vs. 50% with placebo), and increased the likelihood of patients having stable FVC — 64% lenabasum vs. 35% placebo. The percentage of participants with improved FVC (by more than 5%) was similar in the two groups.
A lower decline in FVC also was seen in patients with interstitial lung disease comparing 20 mg lenabasum with a placebo.
As reported previously, lenabasum was generally safe and well-tolerated, with no new safety findings. Dizziness (18.3% of patients on lenabasum vs. 4.9% placebo) and dry mouth (5% lenabasum vs. 1.6% placebo) were among adverse events (side effects) that occurred in at least 3% more people in the 20 mg lenabasum group compared to the placebo group. Treatment with lenabasum was not associated with immunosuppression.
Corbus is still analyzing results from the trial and may explore the therapy’s potential as a treatment for lung involvement in scleroderma in a future study.
Lenabasum was granted orphan drug and fast track designations by the U.S. Food and Drug Administration, and orphan drug designation from the European Medicines Agency for the treatment of scleroderma.