Zilucoplan Shows Improvement in Scores for Generalized Myasthenia Gravis

In the RAISE study (NCT04115293), zilucoplan (RA101495; UCB, Atlanta, GA) significantly improved scores on the Myasthenia Gravis Activities of Daily Living (MG-ADL) in adults with acetylcholine receptor autoantibody positive (antiAChR+) generalized myasthenia gravis (gMG). 

Participants treated with zilucoplan (0.3 mg/kg daily) had improvements as soon as 1 week and a mean placebo-adjusted improvement of 2.12 points in the MG-ADL score at 12 weeks (P<.001).Improvement in gMG symptoms was also seen, as measured with the Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite (MGC), and Myasthenia Gravis Quality of Life 15-Item revised (MG-QoL15r). A significantly higher proportion of participants treated with zilucoplan vs placebo achieved at least 3- and 5-point improvements on the MG-ADL and QMG, respectively.  

“The results from the RAISE study are an exciting development in the gMG treatment paradigm and reinforce the critical role that complement inhibition could play for physicians treating patients with this debilitating illness. By targeting the underlying mechanisms of gMG at the neuromuscular junction, complement inhibitors like zilucoplan have the potential to provide rapid, consistent disease control earlier in the disease course. 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.

Zilucoplan is a self-administered subcutaneous peptide inhibitor of complement C5. Participants in the study were randomly assigned to receive zilucoplan (n=86) or placebo (n=88). The rate of adverse events with zilucoplan vs placebo was similar (76.7% vs 70.5%), and the most common adverse events observed with zilucoplan treatment were diarrhea, headache, site bruising, and MG worsening.

These data are being presented at the 14th Myasthenia Gravis Foundation of America (MGFA) International Conference on Myasthenia and Related Disorders, May 10-12, 2022.