RARE Daily

EC Approves UCB’s Zilbrysq for Generalized Myasthenia Gravis

December 4, 2023

Rare Daily Staff

The European Commission granted a marketing authorization for UCB’s Zilbrysq as an add-on to standard therapy for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor antibody-positive.

Generalized myasthenia gravis (gMG) is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterized by dysfunction and damage at the neuromuscular junction (NMJ). Several factors are understood to be drivers of gMG disease pathology, including the complement cascade, immune cells, and pathogenic Immunoglobulin G (IgG) autoantibodies.

In anti-acetylcholine receptor (AChR) antibody-positive gMG, pathogenic AChR autoantibodies (IgG1 and IgG3) initiate the classical complement pathway, leading to the cleavage of C5 and the MAC (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 to preserve neuromuscular transmission. Myasthenia gravis has a global prevalence of 100–350 cases per every 1 million people.

Zilbrysq (zilucoplan) is the first once-daily subcutaneous, targeted peptide inhibitor of complement component 5. It is the only once-daily gMG target therapy for self-administration by adult patients with anti-AChR antibody-positive gMG. As a complement C5 inhibitor, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted mechanism of action. Benefits of self-administered treatment compared with intravenously administered treatments can include reduced traveling time to and from hospitals, decreased interference with work obligations, and increased independence. Unlike monoclonal antibody C5 inhibitors, as a peptide, zilucoplan can be used concomitantly with intravenous immunoglobulin and plasma exchange, without the need for supplemental dosing.

The European Commission’s approval of zilucoplan is supported by safety and efficacy data from the RAISE study, published in The Lancet Neurology in May 2023. The RAISE study was a multi-center, phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy, safety profile, and tolerability of zilucoplan in adult patients with anti-acetylcholine receptor (AChR) antibody-positive gMG. Patients were randomized in a 1:1 ratio to receive daily subcutaneous (SC) injections of 0.3 mg/kg zilucoplan or placebo for 12 Weeks. The study demonstrated that zilucoplan delivered rapid, consistent, clinically meaningful and statistically significant improvements in different patient- and clinician-reported outcomes at week 12 in a broad population of adult patients with mild-to-severe anti-AChR antibody-positive gMG.2

As included within the zilucoplan EU Summary of Product Characteristics, the most frequently reported adverse reactions were injection site reactions (injection site bruising (13.9 percent) and injection site pain (7.0 percent)) and upper respiratory tract infections (nasopharyngitis (5.2 percent), upper respiratory tract infection (3.5 percent) and sinusitis (3.5 percent)).

European approval of zilucoplan follows approvals by the U.S. Food and Drug Administration for the treatment of generalized myasthenia gravis (gMG) in adult patients who are AChR antibody-positive and by the Japanese Ministry of Health, Labour and Welfare for the treatment of gMG in adult patients who inadequately respond to steroids or other immunosuppressants.

“With the European Commission’s approval of zilucoplan I’m very excited that UCB is taking another important step forward in delivering patient value to the gMG community, giving clinicians an opportunity to address complement activation in gMG with a once-daily, self-administered, subcutaneous treatment option,” said Jean-Christophe Tellier, CEO, UCB.

The approval of zilucoplan from the EC is valid in all EU member states, as well as in the European Economic Area countries Iceland, Liechtenstein, and Norway.

UCB is committed to making zilucoplan available to patients as quickly as possible and anticipates European availability will commence in the first quarter of 2024.

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