FDA Approves UCB’s Zilbrysq for the Treatment of Adults with Generalized Myasthenia Gravis

Rare Daily Staff

The U.S. Food and Drug Administration approved UCB’s Zilbrysq 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.

Zylbrysq (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 FDA 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 antibody-positive gMG. The study demonstrated that zilucoplan delivered rapid, consistent, and statistically significant benefits 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. The most common adverse reactions (≥10 percent) in patients with gMG were injection site reactions, upper respiratory tract infection, and diarrhea.

The approval of zilucoplan follows the company’s neonatal Fc receptor (FcRn) blocker Rystiggo, which was approved earlier this year by the FDA under Priority Review designation for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive and provides the option of addressing either complement activation or pathogenic auto-antibodies for appropriate patients.

“Until now, people living with gMG have only had access to C5 therapy intravenously, which can be inconvenient and time consuming. Now, with the option of zilucoplan, 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,” said Iris Loew-Friedrich, executive vice president and chief medical officer at UCB.

In September 2023, the Committee for Medicinal Products for Human Use of the European Medicines Agency issued a positive opinion recommending granting marketing authorization for zilucoplan in the European Union as an add-on to standard therapy for the treatment of gMG in adult patients who are anti acetylcholine receptor antibody positive. A final decision on approval in the EU is expected before the end of the year, in line with the EMA’s standard review timeline.

Zilucoplan was approved in Japan in September 2023 for the treatment of gMG in adult patients who inadequately respond to steroids or other immunosuppressants.

Photo: Iris Loew-Friedrich, executive vice president and chief medical officer at UCB