Phase 3 Trial to Evaluate Safety & Efficacy of Dermatomyositis Treatment, Lenabasum

Plans for a phase 3 trial to investigate lenabasum as a potential treatment for dermatomyositis, a rare and often fatal multisystem inflammatory autoimmune disease affecting muscle and skin, have been announced by Corbus Pharmaceuticals Holdings, Inc.

The international, double-blind, randomized, placebo-controlled, phase 3 trial will test the safety and efficacy of lenabasum in approximately 150 adults with dermatomyositis over the course of 1 year, beginning at the end of 2018.

“Current treatment options for dermatomyositis patients are largely restricted to immunosuppressive drugs, including high-dose corticosteroids as first-line treatment,” said Barbara White, MD, chief medical officer of Corbus, in a recent statement. “Dermatomyositis is a rare disease, the unmet medical need for new treatments is great, and lenabasum treatment was associated with improvement in multiple efficacy outcomes in the phase 2 study.”

Participants with dermatomyositis will be randomized in the phase 3 trial to receive lenabasum 20 mg twice per day, lenabasum 5 mg twice per day, or placebo twice per day in a 2:1:2 ratio. The primary efficacy outcome will be the American College of Rheumatology (“ACR”)/ European League Against Rheumatism 2016 Total Improvement Score (“TIS”) in myositis, a composite measure of improvement from baseline in six endpoints: Physician Global Activity, Patient Global Activity, Health Assessment Questionnaire, Manual Muscle Testing, and measurement of muscle enzymes and extra muscular activity, according to a recent news release. A secondary efficacy outcome will be the Change in the Cutaneous Dermatomyositis Activity and Severity index (“CDASI”) activity score.

“Our goal is to approach the US Food and Drug Administration (FDA) about registration of lenabasum for treatment of dermatomyositis should the data from this single phase 3 study be positive,” added Dr White. “Our confidence in moving into phase 3 testing in dermatomyositis is anchored in consistent and often medically meaningful improvements in multiple physician- and patient-reported outcomes in phase 2 testing.”

Plans for the phase 3 trial are supported by favorable data gleaned from a phase 2 trial, which involved patients with refractory skin-predominant dermatomyositis. In this trial, treatment with lenabasum was associated with an improvement of minus 9.4 points from baseline in the CDASI activity score, a validated outcome measure of skin disease severity, at the end of the 16-week double-blinded placebo-controlled portion of the trial. In CDASI activity score, an improvement of minus 5 points or more is considered medically meaningful.

At the end of 28 weeks open-label dosing, an improvement in CDASI activity score was observed, as it increased further to minus 15.4 points. Investigators report that more than 80% of subjects achieved ≥ 10-point improvement from the start of the phase 2 trial and approximately 50% achieved low skin disease activity.

Consistent improvement in other measures of skin disease activity, physician global assessment, patient global assessment, and patient-reported function and symptoms during the double-blinded placebo-controlled portion of the trial were also attributed to the lenabasum treatment. In the ongoing open-label extension phase 2 trial, multiple key efficacy outcomes further improved as well.

"If approved, lenabasum would be the first ever drug approved by the FDA based on results of double-blind placebo controlled studies," said Dr White exclusively to Rare Disease Report®. "Currently, the 80,000 Americans living with DM are treated with potent immunosuppressive drugs that are associated with often very serious side effects while still experiencing mortality rates of 30%. In a recent Phase 2 study, lenabasum improved skin as well as patient reported outcome in DM patients in addition to changes in disease-specific inflammatory biomarkers. The potential impact of lenabasum on these patients, if approved, could be very significant. Our aim is to launch our Phase 3 study so that we generate data in late 2020."

Lenabasum is a synthetic, oral, small-molecule, endocannabinoid-mimetic, selective cannabinoid receptor type 2 (CB2) agonist that preferentially binds to CB2 expressed on activated immune cells and fibroblasts. Since CB2 activation triggers physiologic pathways that resolve inflammation, speed bacterial clearance, and halt fibrosis, it also causes the production of specialized pro-resolving lipid mediators that activate an endogenous cascade responsible for the resolution of inflammation and fibrosis, while reducing production of multiple inflammatory mediators.

Lenabasum received an orphan drug designation from the FDA this past July (2018).

Aside from dermatomyositis, lenabasum is also being investigated as a potential treatment for diffuse cutaneous systemic sclerosis and cystic fibrosis in phase 2 trials.