Zilucoplan Prevents Myasthenia Gravis Worsening, Lowers Rescue Therapy Use

Zilucoplan significantly prevented worsening of generalized myasthenia gravis (MG) symptoms and necessitated less frequent use of rescue therapies compared with placebo, according to study results presented at the 2023 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, held from November 1 to 4 in Phoenix, Arizona.

Zilucoplan is a complement component 5 inhibitor currently being investigated for the treatment of acetylcholine receptor autoantibody-positive (AChR+) generalized MG. It is unknown whether patients with AChR+ generalized MG experience worsening of MG symptoms while taking zilucoplan, if the worsening of MG symptoms is related to the treatment, and, consequently, if rescue therapies are required more frequently for breakthrough MG symptoms during zilucoplan treatment.

An international team of researchers conducted a phase 3, double-blind, randomized, placebo-controlled trial (RAISE; ClinicalTrials.gov Identifier: NCT04115293) to determine whether MG symptoms worsened during treatment with zilucoplan. They randomly assigned 86 individuals with AChR+ generalized MG to the treatment group and 88 individuals to the placebo group. The treatment group received daily subcutaneous injections of zilucoplan dosed at 0.3 milligrams per kilogram of body weight (mg/kg) over 12 weeks.

Worsening of MG symptoms was defined as a 3-point increased score or greater on the MG Activities of Daily Living (MG-ADL) or a 5-point increased score or greater on the Quantitative MG (QMG). The researchers also recorded the concomitant need for rescue therapies, such as plasma exchange or intravenous immunoglobulin (IVIg) therapy, during MG symptom worsening.

Worsening of MG symptoms occurred more frequently in the placebo group compared with the zilucoplan group (25% vs 10.5%; nominal P <.05, not multiplicity-controlled). Treatment-emergent adverse events (AEs) occurred in 8 participants in the placebo group and all 8 (100%) required rescue therapy. Similar treatment-emergent AEs contributing to worsening of MG symptoms occurred in 9 participants in the zilucoplan group; however, in contrast, only 2 of these 9 patients (22.2%) required rescue therapy.

“A significantly lower proportion of zilucoplan patients experienced MG worsening, and, of those who had TEAE [treatment-emergent adverse events] of MG worsening, a lower proportion required rescue therapy at any time during RAISE, compared with placebo,” the researchers concluded.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures. The study was funded by UCB Pharma.