Lenabasum Use Seen to Lessen Inflammation, Fibrosis in Phase 2 dcSSc Trial

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by Joana Carvalho |

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FCX-013 clinical trial

Treatment with lenabasum is safe and leads to clinically meaningful improvements in people with diffuse cutaneous scleroderma (dcSSc), results from Phase 2 trial show.

The therapy is now being tested in this trial’s extension study, as well as in a Phase 3 trial in adults with dcSSc.

Trial findings were reported in the study, “Safety and efficacy of lenabasum in a phase 2 randomized, placebo‐controlled trial in adults with systemic sclerosis,” published in the journal Arthritis & Rheumatology.

Lenabasum, formerly known as anabasum, is an oral medication being developed by Corbus Pharmaceuticals as a potential treatment of scleroderma and other chronic inflammatory diseases that lead to tissue scarring (fibrosis).

It works by activating a type of protein receptors found on the surface of immune cells and fibroblasts (connective tissue cells) called cannabinoid receptor type 2 (CB2). By activating these receptors, lenabasum mimics the effects of naturally produced endocanabinoids, molecules that instruct cells to turn off inflammatory responses, lowering inflammation and reducing fibrosis.

Lenabasum’s safety, tolerability, efficacy, and pharmacological properties are being investigated in a Phase 2 trial (NCT02465437) in dcSSc patients.

The study, sponsored by Corbus, is being conducted at nine clinical sites across the U.S. and enrolled 42 adults with dcSSc who had been living with scleroderma for up to six years. It was composed by an initial double-blind phase lasting 12 weeks, followed by its current open-label (no placebo group) extension phase.

During the first phase, participants were randomly assigned to either lenabasum or a placebo, plus their stable standard of care. For its first four weeks, patients on lenabasum were given the medication at a dose of 5 mg or 20 mg once-a-day, or 20 mg twice daily. For its eights weeks, all those assigned to lenabasum took the therapy at 20 mg twice-a-day.

During the trial’s extension, all patients who completed the first phase started receiving the medication at a dose of 20 mg twice-a-day.

Early data from the ongoing extension part showed that lenabasum led to durable, clinically meaningful improvements in patients’ lung function and skin health after more than two years on treatment.

Investigators now reported findings from the study’s first phase, in which safety and efficacy assessments were performed every four weeks until week 16.

Compared to placebo, lenabasum led to greater improvements in patients’ overall health status — assessed by the American College of Rheumatology Combined Response Index in Systemic Sclerosis (ACR-CRISS), a composite measure of disease state and organ damage — starting at week 8 and reaching a maximum at week 16.

Improvements in skin health and patient-reported outcomes were also greater among those on lenabasum.

Analyses of skin biopsies taken at the study’s start and at week 12 showed that lenabasum led to stronger reductions in inflammation and tissue scarring compared to placebo.

Adverse events were experienced by more than half of the patients receiving lenabasum (63%) and those given a placebo (60%)  over the course of the study.

The most frequent adverse events observed in both groups included dizziness, fatigue, headache, joint pain, upper respiratory tract infections, and nausea.

No serious adverse event was deemed related to lenabasum’s use, and no deaths were reported.

“Overall, the results of this Phase 2 study indicate potential efficacy in lenabasum in dcSSc patients, with consistent improvement in multiple physician- and patient-reported outcomes and apparent improvement in underlying disease mechanisms as shown in skin biopsies,” the researchers wrote.

Further studies, however, are needed to investigate lenabasum’s therapeutic potential for scleroderma and other inflammatory and fibrotic diseases, they added.

A Phase 3 trial (NCT03398837), called RESOLVE-1, is assessing the efficacy and safety of lenabasum in 365 adults with dcSSc. As the previous Phase 2 trial, RESOLVE-1 will evaluate effectiveness based on changes in ACR-CRISS scores, and other measures of skin involvement and lung function.

In a press release, Corbus announced that top-line findings from RESOLVE-1 are expected this summer.