Lenabasum Showing Promise in Systemic Scleroderma

Ingrid Hein

June 14, 2018

AMSTERDAM — For patients with diffuse cutaneous systemic sclerosis, an autoimmune disease for which there are few treatment options, lenabasum (JBT-101, Corbus Pharmaceuticals) shows potential, new data from an open-label extension show.

"Our results are very encouraging," said principle investigator Robert Spiera, MD, from Weill Cornell Medical College in New York City.

"Lenabasum has a favorable safety profile and is well tolerated," he told a packed presentation hall here at the European League Against Rheumatism Congress 2018. Improvements were seen "in patient-reported skin symptoms and functioning."

"This is a population that's desperately in need of safe, effective therapies, particularly ones that are not immunosuppressive," Spiera told Medscape Medical News. "When something safe proves effective, it's enormous for our patients; we want to avoid exposing our patients to toxic therapies."

The diffuse cutaneous subtype affects about one in four of the 300,000 people with scleroderma in the United States, according to the Scleroderma Foundation.

This is a population that's desperately in need of safe, effective therapies, particularly ones that are not immunosuppressive.

There are several agents that slow progression of the disease, but there is no standard therapy for systemic sclerosis. Symptoms of systemic sclerosis include hardening of the skin, changes in skin pigmentation, joint pain, gastroesophageal reflux disease, and irritable bowel syndrome. The disease can lead to, among other things, Raynaud's phenomenon, Sjögren's syndrome, pulmonary fibrosis, renal crisis or failure, and lung, heart, and kidney disease.

In a previous phase 2 double-blind placebo-controlled trial of lenabasum (NCT02465437), results showed safety, tolerability, and clinical benefit in patients with the diffuse cutaneous subtype. The oral, synthetic, nonimmunosuppressive small molecule — a selective cannabinoid receptor type 2 agonist — activates resolution of the innate immune response.

To assess outcomes more closely, Spiera and his colleagues enrolled 36 of the 38 eligible patients from the phase 2 trial in an open-label extension. There was a time lag of 5 to 56 weeks between the two studies, and patients were not on lenabasum during that period.

Extension participants received lenabasum 20 mg twice a day.

Outcomes at 52 Weeks

Spiera reported results for the 25 patients who had completed 52 weeks of treatment in the open-label extension at the time of data cutoff.

Median score on the Combined Response Index in Diffuse Systemic Sclerosis (CRISS) improved 56% from the beginning of the phase 2 trial.

During the open-label extension, mean Physician Global Assessment score decreased by 0.9, and mean 5-D itch scale score decreased by 2.3.

Fifty percent of patients achieved a 95% CRISS response, Spiera reported. "And we saw a significant improvement in skin scores."

Of the 36 participants, 33 reported adverse events, including one patient who developed renal crisis. Adverse events were related to lenabasum in only seven patients.

The most common events were upper respiratory tract infection (22%), urinary tract infection (14%), diarrhea (11%), skin ulcers (11%), and mild intermediate dizziness (8%).

The open-label nature of the study could have contributed to some of the effects, Spiera and his colleagues acknowledge.

"There's no doubt this is an exciting drug to be testing," said Christopher Denton, PhD, from University College London, who is a principle investigator of an international phase 3 clinical trial of lenabasum (NCT03398837), with results expected in 2020.

Evidence that patients got worse between the original trial and the open-label extension, when they were not taking the drug, is impressive, he added. "There was some rebound worsening in CRISS and skin tests in the interval; that's supportive evidence."

Spiera has disclosed no relevant financial relationships. Denton reports financial relationships with Inventiva, CSL Behring, GSK, Bayer, Actelion, Roche, Boehringer Ingelheim, EMD Serono, and sanofi-aventis.

European League Against Rheumatism (EULAR) Congress 2018: Abstract OP0006. Presented June 13, 2018.

Follow Medscape on Twitter @Medscape and Ingrid Hein @ingridhein

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