Understanding Zilucoplan’s Positive Impact on Fatigue in Myasthenia Gravis: Michael D. Weiss, MD, FAAN

WATCH TIME: 6 minutes

“When using this methodology, it suggests that the effects of fatigue are profound and whether that's going to be true for patients in the real world, we will soon see. But we're hopeful and optimistic that this therapy will have a market impact and fatigue in MG. We're looking forward to hearing from patients that they are doing better with their fatigue as a result.”

Myasthenia gravis (MG), a rare neuromuscular disorder, is marked by a variable combination of weakness of the eye, bulbar, respiratory, axial, and limb muscles. Since the condition affects postsynaptic cholinergic receptors, this results in symptoms of muscular fatigue.¹ The clinical signs for this symptom can be subtle and variable which can then often lead to many differentials. Based on this, inappropriate tests may be performed on patients and delay their diagnosis.² Overall, myasthenic fatigue has a marked negative impact on quality of life in patients with MG and remains a significant unmet need.

A new post hoc analysis of the phase 3 RAISE study (NCT94115293) and its open-label extension, RAISE-XT (NCT04225871), showed that treatment with zilucoplan (Zilbrysq; UCB Pharma) significantly and clinically meaningfully improved myasthenic fatigue compared with placebo, with further improvements that were sustained for up to 60 weeks.^{3 T}hese findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held November 1-4, in Phoenix, Arizona, by lead author Michael D. Weiss, MD, FAAN, director of the neuromuscular diseases division at the University of Washington (UW), and colleagues.

At the meeting, Weiss, who also serves as a professor of neurology and adjunct professor of rehabilitation medicine at UW, sat down in an interview with NeurologyLive® to discuss what zilucoplan is, and its impact on fatigue. Additionally, Weiss spoke about the implications the sustained effects of the treatment have for patients with MG and shared the next potential steps in this research.

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REFERENCES
1. Dewilde S, Phillips G, Paci S, De Ruyck F, Tollenaar NH, Janssen MF. The Burden Patients with Myasthenia Gravis Experience in Terms of Breathing, Fatigue, Sleep, Mental Health, Discomfort and Usual Activities in Comparison to the General Population. Adv Ther. 2023;10.1007/s12325-023-02704-w. doi:10.1007/s12325-023-02704-w
2. Gosain D, Das T. Myasthenia Gravis Presenting as Bulbar Palsy. Cureus. 2023;15(9):e46082. Published 2023 Sep 27. doi:10.7759/cureus.46082
3. Weiss MD, Freimer M, Maniaol A, et al. Effect of Zilucoplan on Fatigue in Generalized Myasthenia Gravis in the Phase 3 RAISE and RAISEXT Studies. Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting; November 1-4, 2023; Phoenix, AZ. Abstract 285.