Positive results were announced from two phase 3 studies evaluating zilucoplan and rozanolixizumab in adults with generalized myasthenia gravis (gMG).

Zilucoplan is a synthetic, macrocyclic peptide inhibitor of complement component 5 (C5). The multicenter, randomized, double-blind, placebo-controlled RAISE study (ClinicalTrials.gov Identifier: NCT04115293) included 174 adults with gMG. Patients were randomly assigned 1:1 to receive zilucoplan or placebo subcutaneously once daily for 12 weeks. 

Results showed that zilucoplan met the primary endpoint demonstrating a placebo-corrected mean improvement of 2.12 points in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score at week 12 (P <.001). Zilucoplan was also associated with statistically significant improvements in the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Composite score, and the Myasthenia Gravis – Quality of Life revised score. 

Significant improvements for all endpoints were observed as early as week 1. Moreover, a significantly greater proportion of patients in the zilucoplan arm achieved at least a 3-point reduction on the MG-ADL score and at least a 5-point reduction in QMG score at week 12 compared with placebo. The most common treatment-emergent adverse events (TEAE) reported were injection site bruising, headache, diarrhea, and MG worsening. 

“These findings are an encouraging sign that we may be able to meet patients’ needs effectively, with treatments that are minimally invasive and well tolerated,” said James F. Howard, MD, Distinguished Professor of Neuromuscular Disease, Professor of Neurology, Medicine and Allied Health, The University of North Carolina at Chapel Hill School of Medicine and lead investigator in the RAISE trial.

Rozanolixizumab is a humanized monoclonal antibody that binds with high affinity to human neonatal Fc receptor (FcRn). The investigational treatment is designed to block the interaction of FcRn and immunoglobulin G (IgG), accelerating the catabolism of antibodies and inducing the removal of pathogenic IgG autoantibodies. 

The multicenter, randomized, double-blind, placebo-controlled MycarinG study (ClinicalTrials.gov Identifier: NCT03971422) included 200 adults with gMG. Patients were randomly assigned 1:1:1 to receive either rozanolixizumab 7mg/kg, rozanolixizumab 10mg/kg, or placebo subcutaneously.

Findings demonstrated that treatment with rozanolixizumab met the primary endpoint demonstrating a placebo-corrected mean improvement of 2.586 points at the 7mg/kg dose and 2.619 points at the 10mg/kg dose in the MG-ADL compared with placebo (both doses P <.001). Rozanolixizumab also reduced the mean maximum total IgG levels by more than 70% (71% for 7mg/kg and 78% for 10mg/kg); anti-AChR autoantibody levels decreased over the treatment period in line with the total IgG reduction.

Rozanolixizumab was well tolerated with the most frequently reported TEAE being headache. Other common TEAEs included diarrhea, pyrexia and nausea.

“The results from the MycarinG study are extremely encouraging, and demonstrate the potential of rozanolixizumab as a new, effective and flexible treatment option to help ease the day-to-day burden of this challenging disease and improve treatment outcomes for patients,” said Professor Vera Bril, Professor of Medicine (Neurology), University of Toronto, Director of the Neuromuscular Section, Division of Neurology, University of Toronto and University Health Network, Toronto, and lead investigator of the MycarinG study.

UCB expects to file regulatory submissions for both zilucoplan and rozanolixizumab later this year.


UCB presents efficacy and safety results for zilucoplan and rozanolixizumab in generalized myasthenia gravis. News release. UCB, Inc. Accessed March 16, 2022. https://www.prnewswire.com/news-releases/ucb-presents-efficacy-and-safety-results-for-zilucoplan-and-rozanolixizumab-in-generalized-myasthenia-gravis-301543626.html