FDA Approves Zilucoplan for Generalized Myasthenia Gravis in AChR Antibody-Positive Adults


The approval marks the first and only once-daily target therapy for generalized myasthenia gravis for self-administration in this patient population.

Zilucoplan (Zilbrysq; UCB, Inc.) has been granted FDA approval for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody-positive.

gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease. It is characterized by dysfunction and damage at the neuromuscular junction and drivers of the disease pathology include the complement cascade, immune cells, and pathogenic immunoglobulin G autoantibodies.

“For people with gMG, the unpredictable nature of the severity and frequency of symptoms can be debilitating and can have a substantial impact on many aspects of their day-to-day lives,” said James F. Howard, MD, Distinguished Professor of Neuromuscular Disease and professor of neurology, medicine, and allied health at the university of North Carolina at Chapel Hill School of Medicine and lead investigator in the RAISE trial, in a press release. “In addition to muscle weakness, people living with gMG experience fatigue, affecting their overall quality of life.”

In anti-AChR antibody-positive gMG, pathogenic AChR autoantibodies (IgG1 and IgG3) initiate the classical complement pathway, leading to the cleavage of C5 and the membrane attack complex formation, damage to the NMJ, loss of AChRs, and subsequent impaired synaptic transmission. Preventing MAC formation reduces damage to the post-synaptic membrane, reduces disruption of ionic channel conductance, and helps preserve neuromuscular transmission.

Zilucoplan is the first once-daily subcutaneous, targeted peptide inhibitor of complement component 5 (C5 inhibitor) and is the only once-daily gMG target therapy for self-administration by adults with anti-AChR antibody-positive gMG. Benefits of self-administration compared to intravenous (IV) administration include reduced travel time, decreased interference with work and family obligations, and increased independence. As a peptide, zilucoplan can be used concomitantly with IV immunoglobulin and plasma exchange, without supplemental dosing.

The approval is supported by safety and efficacy data from the RAISE study (NCT04115293), published in May 2023. Patients were randomized 1:1 to receive daily subcutaneous injections of 0.3 mg/kg zilucoplan or placebo for 12 weeks.

The primary endpoint was change from baseline to week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score, which assesses activities such as breathing, talking, swallowing, and being able to rise from a chair. Efficacy was also measured as a secondary endpoint using the Quantitative Myasthenia Gravis (QMG) total score, which assesses muscle weakness.

According to the findings, zilucoplan delivered rapid, consistent, and statistically significant benefits among different patient- and clinician-reported outcomes at week 12 in a broad population of adults with mild-to-severe anti-AChR-antibody positive gMG. At week 12, treatment with zilucoplan demonstrated a statistically significant improvement from baseline for MG-ADL total score and QMG total score.

The most common adverse reactions were injection site reactions, upper respiratory tract infection, and diarrhea.

“Until now, people living with gMG have only had access to C5 therapy intravenously, which can be inconvenient and time consuming,” said Iris Loew-Friedrich, executive vice president and chief medical officer at UCB, in the press release. “Now, with the option of Zilbrysq, a self-administered once-daily, subcutaneous targeted complement C5 inhibitor, we hope a broad population of mild-to-severe adult patients with AChR-antibody-positive gMG will be able to have greater independence.”


UCB announces US FDA approval of Zilbrysq (zilucoplan) for the treatment of adults with generalized myasthenia gravis. News release. UCB. October 17, 2023. Accessed October 18, 2023. https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/ucb-announces-us-fda-approval-of-zilbrysq-zilucoplan-for-the-treatment-of-adults-with-generalized-myasthenia-gravis

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