Myasthenia Agent Zilucoplan Continues to Show Positive Efficacy in Long-Term Extension


In participants who received placebo during the parent studies, rapid improvements were observed as early as week 1 after switching to zilucoplan, and continued through week 12 of the extension period.

Angela Genge, MD, FRCP, director of the ALS Center of Excellence for Research and Patient care at McGill University

Angela Genge, MD, FRCP

Interim data from RAISE-XT, a phase 3, open-label extension (OLE) study of UCB Pharma’s zilucoplan, an agent currently under review for myasthenia gravis (MG), showed favorable long-term safety profile, with positive efficacy in those who continued treatment from the double-blind period and those who switched from placebo.

RAISE-XT, an ongoing study, featured 199 patients with MG who participated in previously conduced phase 2 (NCT03315130) and phase 3 (NCT04115293) studies. Patients self-administered daily subcutaneous injections of 0.3 mg/kg zilucoplan and were assessed on the primary outcome of treatment-emergent adverse events (TEAEs). At data cutoff (February 18, 2022), participants had a median duration of exposure of 253 days (range, 29-1434) during RAISE-XT and the OLE portion of the phase 2 study for participants who continued in RAISE-XT.

Led by Angela Genge, MD, FRCP, director of the ALS Center of Excellence for Research and Patient care at McGill University, the findings were presented at the 2023 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 19-22, in Dallas, Texas. At the 24-month period, 84.9% (n = 169) experienced a TEAE, and 23.1% (n = 46) documented serious AEs. Between both groups, the most common TEAEs were headache and worsening of MG, both occurring in 16.6% of patients.

Throughout the study, 4 treatment-emergent deaths occurred, all in patients with multiple cardiovascular risk factors, and none of them were considered treatment related. Cardiac arrest was the cause in 2 patients, 1 patient experienced head injury, and 1 had severe pneumonia 2 days prior to death. Infections were reported in nearly half (49.2%) of the cohort, although most (86%) were non-serious.

Myasthenia Gravis Activities of Daily Living (MG-ADL), a measure of efficacy, was rapidly improved throughout the OLE period among those who switched from placebo to zilucoplan. Similarly, the zilucoplan group demonstrated significant improvements on MG-ADL during the OLE (P = .0002). From double-blind study baseline, zilucoplan-treated individuals achieved least square mean changes in MG-ADL score of –6.30 (95% CI, –7.44 to –5.15). These results were similar for the placebo-switch group, with score reductions of –6.32 (95% CI, –8.00 to –4.65). Scores on key secondary outcomes such as Qualitative Myasthenia Gravis score, Myasthenia Gravis Composite score (MGC), and Myasthenia Gravis Quality of Life 15-item-revised, were similar across both treatment groups as well.

In November 2022, the FDA accepted UCB’s new drug application for zilucoplan using data from the pivotal phase 3 RAISE study. In that trial, 0.3 mg/kg daily of zilucoplan met its primary end point in MG-ADL score at week 12, with placebo-correct mean improvements of 2.09 points. Zilucoplan not only met its primary end point, but it showed statistically significant improvements in secondary end points such as QMG score, MGC, and Myasthenia Gravis Quality of Life 15-item Scale score relative to placebo. These improvements were seen as early as 1 week after treatment initiation.2

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1. Genge A, Hussain Y, Kaminski HJ, et al. Safety and tolerability of zilucoplan in RAISE-XT: a multicenter, open-label extension study in patients with myasthenia gravis. Presented at: MDA 2023; February 19-22; Dallas, TX. Abstract 145.
2. UCB presents efficacy and safety results for zilucoplan and rozanolixizumab in generalized myasthenia gravis. News release. UCB Pharma. May 10, 2022. Accessed November 14, 2022.
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