UCB Reports Positive Results in Phase 3 Generalized Myasthenia Gravis Study
May 10, 2022
UCB reported positive results from two phase 3 studies evaluating its experimental treatments, zilucoplan and rozanolixizumab, in adults with the rare autoimmune condition generalized myasthenia gravis.
The study met its primary endpoint with zilucoplan showing a placebo-corrected mean improvement of 2.12 points in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 12. Significant improvement in the MG-ADL was observed from Week 1.
Generalized myasthenia gravis (gMG) is a rare and chronic autoimmune disease where IgG autoantibodies disrupt communication between nerves and muscles, causing debilitating and potentially life-threatening muscle weakness. Approximately 85 percent of people with MG progress to gMG within 24 months, where muscles throughout the body may be affected. Patients with confirmed anti-acetylcholine receptor (AChR) antibodies account for approximately 85 percent of the total gMG population.
Zilucoplan, a self-administered, subcutaneous (SC) peptide inhibitor of complement component 5 (C5 inhibitor). Rozanolixizumab is an SC-infused monoclonal antibody targeting the neonatal Fc receptor (FcRn).
Data from the phase 3 RAISE trial demonstrated treatment with zilucoplan resulted in clinically meaningful and statistically significant improvements in key gMG-specific outcomes compared with placebo in patients with acetylcholine receptor autoantibody positive (AChR+) gMG.
All key secondary endpoints were also met, including statistically significant improvements in the Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Composite (MGC) and Myasthenia Gravis Quality of Life 15-Item revised (MG-QoL15r), with significant improvement observed from Week 1. The proportion of patients on zilucoplan who responded to treatment by at least a 3-point reduction on MG-ADL and at least a 5-point reduction in QMG were also significantly higher than placebo.
A favorable safety profile and good tolerability was observed, consistent with prior data, showing a similar rate of treatment-emergent adverse events (TEAEs) between zilucoplan (76.7 percent) and placebo (70.5 percent). The most common TEAEs were injection site bruising, headache, diarrhea, and MG worsening.
“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,” said James Howard, 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. “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.”
Due to the fluctuating and unpredictable nature of gMG and the subjectivity of symptoms, patient reported outcomes (PROs) help provide greater insight into disease impact and more granular detail on the effect of treatments than traditional endpoints. Within the MycarinG study, the MG Symptoms PRO measure, which was developed by UCB with patients, was used to assess a series of quality-of-life measures, including muscle weakness fatigability, physical fatigue and bulbar muscle weakness, throughout the treatment and observation periods (poster 64)3.
All three MG Symptoms PRO scales or subdomains showed significant improvement from baseline with rozanolixizumab doses compared with placebo at Day 43, indicating treatment with rozanolixizumab improves patients’ symptoms and their ability to undertake daily activities. Further evaluation of the MG Symptoms PRO measure is ongoing.
UCB anticipates filing regulatory submissions for both zilucoplan and rozanolixizumab later this year.
Author: Rare Daily Staff
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