The research, “Safety and Efficacy of Lenabasum at 21 Months in an Open-Label Extension of a Phase 2 Study in Diffuse Cutaneous Systemic Sclerosis Subjects,” was presented by Robert Spiera, MD, the trial’s principal investigator, at the recent 2019 American College of Rheumatology and Association of Rheumatology Professionals Annual Meeting, in Atlanta, Georgia.
Lenabasum, developed by Corbus Pharmaceuticals, is an oral investigational treatment designed to activate the cannabinoid receptor type 2, or CB2, in immune cells and fibroblasts. Activation of CB2 reduces inflammation, promotes bacterial clearance, and prevents fibrosis (scarring).
The Corbus-sponsored Phase 2 trial (NCT02465437) aimed to assess the safety, tolerability, pharmacokinetics, and efficacy of lenabasum in 36 adults with dcSSc (mean age of 48 years, mean disease duration of 41 months). Of note, pharmacokinetics refers to how a compound is absorbed, distributed, metabolized, and excreted in the body.
After completing 12 weeks of treatment in Part A, all participants received 20 mg lenabasum twice a day along with their standard-of-care treatments in the open-label extension (OLE), or Part B.
In line with data at 21 months, updated results at 25 months showed that a composite measure of disease state and organ damage — the American College of Rheumatology Combined Response Index in Systemic Sclerosis (ACR-CRISS) score — remained above 0.95 since the 12th month of treatment. A score of 0.6 or greater indicates that clinical improvement is likely.
During the same period, the modified Rodnan Skin Scores — a measure of skin sclerosis — improved (decreased) more than 9.2 points. A decrease of 4 to 5 points in considered clinically significant.
In contrast, mean percent predicted forced vital capacity (FVC), a measure of lung function, declined 2% from the beginning of the study. FVC refers to the amount of air one can exhale after a deep breath.
Skin symptoms, itch, and patient-reported disability and function were either stabilized or continued to improve in months 12 to 25 of the therapy.
“Efficacy outcomes show stable improvement from about 1 year in the OLE or continued improvement in some cases,” the researchers wrote.
No severe or serious adverse events or study discontinuations related to lenabasum were reported as of the analysis cut-off date. Of the 36 patients who began the OLE, 29 (81%) were still participating in the study at 25 months.
All but one participant experienced more than one adverse event. Of these, seven patients experience side effects directly related to lenabasum, which included headache and dizziness.
At the meeting, Corbus also presented a session, with the abstract “Baseline Subject Demographics and Disease Characteristics in a Phase 3 Study of Safety and Efficacy of Lenabasum in Diffuse Cutaneous Systemic Sclerosis,” which addressed an international trial called RESOLVE-1 (NCT03398837).
That study will evaluate the safety and effectiveness of lenabasum in 364 adults with dcSSc on stable standard-of-care medications in a real-world scenario. Two dosages of lenabasum will be compared to a placebo over a one-year period. Participants (76% women, mean age of 50 years) will be divided into three groups based on disease duration.
“The persistently favorable safety profile and durable improvement in efficacy outcomes … support our optimism that the Phase 3 SSc study will show positive data in summer 2020,” Barbara White, MD, chief medical officer and head of research at Corbus, said in a press release.
In addition, Corbus also presented data showing early positive results of lenabasum for the treatment of dermatomyositis.
“We interpret the durable improvement in multiple efficacy outcomes as an indicator showing totality of benefit for these diseases,” added White.
For the treatment of SSc, lenabasum has been granted orphan drug status and fast track designation from the U.S. Food and Drug Administration (FDA), and orphan drug designation from the European Medicines Agency (EMA).
It has also been given orphan drug status by the FDA and the EMA for the treatment of dermatomyositis.