Lenabasum, an investigational treatment of diffuse cutaneous systemic sclerosis by Corbus Pharmaceuticals, was shown to be safe, well-tolerated and of benefit to patients treated for one year in a long-term extension of a Phase 2 trial.
Latest results of the JBT101-SSc-001 study (NCT02465437) will be discussed at the European League Against Rheumatism (EULAR) 2018 Annual Meeting, set for June 13–16 in Amsterdam.
The oral presentation is titled “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,” and will be given by Robert Spiera, MD, director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery, Weill Cornell Medical College in New York. Spiera is also the trial’s principal investigator.
Lenabasum, formerly known as anabasum or JBT-101, is an engineered, oral endocannabinoid-mimetic medicine designed to have a dual action, that of targeting chronic inflammation and fibrosis at the same time.
The investigative molecule selectively binds to the cannabinoid receptor type 2, or CB2, in activated immune cells and fibroblasts. This triggers the production of specialized pro-resolving lipid mediators that can block the pro-inflammatory and pro-fibrotic signals without affecting the immune cells’ primary function, which is to protect the body.
Corbus is evaluating lenabasum’s safety, tolerability and efficacy in a two-part Phase 2 trial. In part one, 42 diffuse cutaneous systemic sclerosis patients were given either 20 mg of lenabasum or a placebo twice daily for 84 days in addition to standard-of-care therapies. Thirty-six of these patients were then enrolled in a one-year and open-label extension study, in which all are receiving the treatment. Data is from this second part.
Analysis of different efficacy outcome measures found the investigative therapy could benefit this patient population.
Data collected from 25 patients who had completed 52 weeks of lenabasum treatment in the extension trial showed an improvement by 56% on their ACR CRISS (American College of Rheumatology’s diffuse cutaneous systemic sclerosis) score — a measure of disease state and organ damage — compared to baseline, or study start, values.
Also, skin thickness improved by 8.6 points, as determined by the modified Rodnan Skin Score, and patients reported a significant reduction of itchy sensations. Global health assessment also revealed that the treatment was beneficial, with reported functional improvements by the end of the study.
No significant changes were reported on lung function (measured by forced vital capacity percent predicted) during the study period, suggesting a stable lung function.
Adverse events were reported in 33 of the 36 extension trial patients, or 92%. One was life-threatening and three others were severe, and events in the remaining 29 patients were mild-to-moderate in severity. Side effects reported in seven of these 29 patients were found to be related to lenabasum use.
The most common side effects were upper respiratory tract infections, urinary tract infections, diarrhea, and skin ulcers.
These results continue to demonstrate that lenabasum has an “acceptable safety and tolerability in diffuse cutaneous systemic sclerosis with no severe or serious adverse events,” the researchers reported, adding “these data support Phase 3 testing of lenabasum for treatment of diffuse cutaneous systemic sclerosis.”
That Phase 3 trial — RESOLVE-1 (NCT03398837) — is now underway, and recruiting across the U.S., with sites also planned for Canada, Australia, Asia and Europe. The study is expected to enroll 354 diffuse cutaneous systemic sclerosis patients who will be treated with either lenabasum at 5 mg or 20 mg, or placebo twice daily for 52 weeks.
Similar to the Phase 2 study, RESOLVE-1 trial researchers will examine changes in skin fibrosis, assess lung function, and other health-related outcomes.
For more information about this Phase 3 trial and how to participate, please visit this link.
Lenabasum has been given Orphan Drug Designation and Fast Track status by the U.S. Food and Drug Administration to treat systemic sclerosis. It has also received Orphan Designation from the European Medicines Agency. These designations are intended to expedite its development and regulatory review.