Topline results from a Phase 2 trial of Ra Pharma’s zilucoplan (previously known as RA101495), a potential self-administered therapy for patients with generalized myasthenia gravis (MG), showed a statistically significant decrease in markers of disease severity, achieving both its primary objectives.
All the trial participants completed the 12-week treatment; 98 percent of them will move into a long-term extension phase where all will receive zilucoplan.
Zilucoplan is a potent inhibitor of complement component 5, a validated therapeutic target in MG.
“Zilucoplan has the potential to become the first convenient, self-administered, complement inhibitor, expanding access for patients living with this chronic, debilitating, neuromuscular disease,” James F. Howard, MD, professor of neuromuscular disease at the University of North Carolina School of Medicine, said in a press release.
Nancy Law, chief executive officer of the Myasthenia Gravis Foundation of America (MGFA), said, “This represents a potential breakthrough for all patients who are struggling every day with their MG, and seeking more effective and convenient treatment options.”
Law said, “This unmet need was highlighted in a recent survey of patients from the MGFA database, where we learned that a majority of patients with MG are not satisfied with their current treatments and are interested in effective, at home, self-injectable treatment options.”
The Phase 2 study (NCT03315130), which enrolled 44 patients with generalized MG in the U.S. and Canada, evaluated the safety and efficacy of zilucoplan, regardless of patients’ prior therapies.
The severity of participants’ disease at the beginning of the study varied from mild (Class II) to severe (Class IV) and had a quantitative MG (QMG) — a test that assesses a patient’s level of muscle weakness — score of 12 or higher.
Participants were randomized to receive one of two daily doses of zilucoplan — 0.1 mg/kg or 0.3 mg/kg — administered under the skin, or a placebo for 12 weeks.
The trial’s main objective was to assess the therapy’s efficacy by measuring changes in the QMG score at the end of the 12-week treatment. The secondary objective was to assess the therapy’s ability to improve participants’ engagement in daily activities using the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale.
The results showed that zilucoplan dosed at 0.3 mg/kg led to a statistically significant reduction in the QMG score of 6.0 points and 3.4 points in the MG-ADL score, relative to the beginning of the study and compared to the placebo group (2.8 points and 2.3 points, respectively).
None of the patients treated with zilucoplan at 0.3 mg/kg required rescue therapy (either with intravenous antibodies or plasma exchange), while this was required to treat 20 percent (three of 15) of the patients in the placebo group.
Zilucoplan dosed at 0.1 mg/kg also led to improvements in both QMG and MG-ADL scores, although less pronounced, with only one patient requiring rescue therapy.
Zilucoplan’s safety profile was in agreement with that of previous studies, with only mild adverse effects that were unrelated to the therapy. No serious adverse effects were detected in participants treated with zilucoplan.
“The rapid, profound, and sustained reductions in QMG and MG-ADL observed in this Phase 2 study confirm that complement inhibition was effective across a wide spectrum of MG patients in this study, whether refractory or non-refractory,” Howard said.
Doug Treco, founder and chief executive officer of Ra Pharma, said: “Designed for subcutaneous self-administration, zilucoplan offers convenience and accessibility, giving it the potential to bring C5 inhibition to the forefront of the treatment paradigm for [generalized MG].”
These findings will be used in conversations with the U.S. Food and Drug Administration to support the launch of a Phase 3 trial to further evaluate zilucoplan, dosed at 0.3 mg/kg versus placebo, in patients with generalized MG.
“We look forward to meeting with regulators to review our Phase 2 data and the design of our planned Phase 3 program with the ultimate goal of transforming the lives of thousands of patients with this disease,” Treco said.