Complement C5 Inhibitor Zilucoplan Is Approved by FDA to Treat MG

UCB Pharma’s investigational agent zilucoplan, a complement C5 inhibitor, to treat patients with myasthenia gravis (MG) has been approved by the U.S. Food and Drug Administration (FDA) under the market name Zilbrysq. The subcutaneously delivered medication is indicated for those with acetylcholine receptor antibody-positive generalized MG (gMG), further expanding the toolbox of options for patients with the disease.

Approval was based on data from the large-scale, double-blind, placebo-controlled, Phase III RAISE study in which zilucoplan demonstrated rapid and clinically meaningful improvements in MG-specific efficacy outcomes. Conducted from 2019 to 2021, 174 eligible patients were included and randomly assigned to either 0.3 mg/kg of zilucoplan (n = 86) or placebo (n = 88) for a 12-week period, followed by an optional open-label extension study. After 12 weeks of treatment, zilucoplan met its primary end point, showing a placebo-corrected mean improvement of 2.09 points on the Myasthenia Gravis Activities of Daily Living score. In secondary efficacy outcomes, investigators observed a clinically meaningful reduction in Quantitative Myasthenia Gravis score after 12 weeks.

In terms of safety, zilucoplan demonstrated a favorable profile, with treatment-emergent adverse events (TEAEs) occurring in 77 percent of patients. The most frequently reported TEAEs were injection-site bruising (16 percent), headache (15 percent), diarrhea (10 percent) and worsening of MG (10 percent). Between the two groups, the incidence of frequently reported TEAEs were similar, except for injection-site bruising, diarrhea, injection-site pain and lipase increase, which were more frequent in the zilucoplan group.

In the zilucoplan group, four patients discontinued because of a TEAE (one each of aphthous ulcer, mouth ulceration, hepatic enzyme increase and COVID-19 leading to death) and two patients discontinued from the placebo group because of a TEAE (hyperemesis gravidarum and cerebral hemorrhage leading to death). Neither death was considered related to the study drug. Of note, a higher incidence of infections occurred in the zilucoplan group than in the placebo group (27 percent vs. 18 percent), which was driven by nonserious upper respiratory tract infections (14 percent vs. 7 percent). No meningococcal or other Neisseria spp infections or anaphylactic reactions occurred in either group.

“For people with gMG, the unpredictable nature of the severity and frequency of symptoms can be debilitating and can have a substantial impact on many aspects of their day-to-day lives. In addition to muscle weakness, people living with gMG experience fatigue, affecting their overall quality of life,” said lead investigator James F. Howard, MD, distinguished professor of neuromuscular disease and professor of neurology at The University of North Carolina at Chapel Hill School of Medicine. “Zilucoplan demonstrated rapid improvements in gMG symptoms at week 12, with differences seen as early as one week, and provides a new treatment option for a broad population of AChR antibody–positive gMG patients. Zilucoplan is designed for continued daily use.”