First Patient Dosed in Phase 3 Trial of Zilucoplan, Ra Pharma Announces

Ra Pharmaceuticals announced the first patient enrolled in RAISE, the company’s Phase 3 clinical trial assessing the effectiveness of zilucoplan  as a therapy for generalized myasthenia gravis (gMG), has started receiving treatment.

Zilucoplan, formerly known as RA101495, is an artificial peptide that binds to complement 5 (C5), blocking its activity and preventing the overactivation of the complement system — a set of more than 50 blood proteins that form part of the body’s immune defenses, which is thought to be involved in the formation of harmful autoantibodies in myasthenia gravis (MG).

In September, the U.S. Food and Drug Administration (FDA) granted the designation of orphan drug to zilucoplan for the treatment of MG. It is being developed to treat people with gMG, immune-mediated necrotizing myopathy (IMNM), and other rare complement system disorders currently lacking treatment options.

RAISE is a 12-week, global, pivotal, randomized, double-blind, placebo-controlled Phase 3 trial that has been designed to assess the effectiveness of zilucoplan when self-administered by an under-the-skin injection at a dose of 0.3 mg/kg, once-a-day, compared to a placebo.

The trial is expected to enroll approximately 130 patients with gMG, including individuals who already had received prior therapies and those who never received any form of treatment.

The trial’s primary outcome will be to evaluate changes in the score of the MG Activities of Daily Living (MG-ADL) scale from baseline to Week 12. The MG-ADL scale will be used to measure the therapy’s ability to improve participants’ engagement in daily activities.

After completing the 12-week treatment period of RAISE, study participants will have the chance to enroll in RAISE-XT, the trial’s open-label, long-term extension study, to continue treatment with zilucoplan. Ra Pharma is expecting to announce top-line findings from RAISE in the beginning of 2021.

“We’re pleased to have dosed the first patient in the RAISE study, a critical milestone in our mission to expand patient access to convenient complement inhibition. With feedback from the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) incorporated into the global Phase 3 trial design, we look forward to advancing zilucoplan through late-stage clinical development in gMG,” Doug Treco, PhD, president and CEO of Ra Pharma, said in a press release.

“With additional indications, including immune-mediated necrotizing myopathy (IMNM) and amyotrophic lateral sclerosis (ALS) recently added to the pipeline, we believe zilucoplan, if successfully developed and approved in these indications, has the potential to support the creation of a leading complement-focused neurology franchise,” Treco said.

The launch of RAISE followed the completion of a Phase 2 clinical trial (NCT03315130) assessing the safety and effectiveness of daily doses of zilucoplan (0.1 mg/kg or 0.3 mg/kg) for the treatment of patients with gMG, compared with a placebo, for 12 weeks.

The study’s findings showed that patients treated with the highest dose of zilucoplan attained a significant reduction of 6.0 points in the quantitative MG (QMG) score and of 3.4 points in the MG-ADL score since the beginning of the trial, compared with those treated with a placebo, who had a reduction of 2.8 points in their QMG score and of 2.3 points in their MG-ADL score. The QMG is a test that measures the degree of muscle weakness.

Zilucoplan was generally safe and well-tolerated by the patients, which was consistent with findings from previous studies. The majority of adverse events (AEs, or side effects)) reported during the trial were considered mild and not directly associated with zilucoplan. No serious AEs linked to treatment with zilucoplan were reported.

“In a Phase 2 clinical trial, zilucoplan achieved rapid, clinically meaningful, and statistically significant reductions in primary and key secondary efficacy endpoints, with a durable treatment effect that was sustained at 24 weeks for patients enrolled in the long-term extension study,” said James F. Howard, MD, distinguished professor of Neuromuscular Disease at the Department of Neurology, University of North Carolina School of Medicine.

“We look forward to building on these data to support zilucoplan’s potential as a simple, convenient, self-administered complement inhibitor for a broad spectrum of patients with gMG,” Howard said.