Next-generation complement C5 inhibitor for anti-AChR Ab+ gMG2
ZILBRYSQ® is indicated as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine recepter (AChR) antibody positive (Ab+).1
Mechanism of Action
In gMG, pathogenic immunoglobulin G (IgG) autoantibodies attack key proteins, most commonly the AChR, on the neuromuscular junction (NMJ).2-4
This prevents AChR binding, reduces receptor density and activates the complement system.4,5
Complement activation following the binding of AChR autoantibodies initiates cleavage of C5 into C5a and C5b by C5 convertase.1,4
C5a is a potent inflammatory mediator, while C5b initiates the terminal complement pathway.2
C5b activates the terminal complement pathway by binding to additional complement proteins to form the MAC, resulting in an influx of ions that cause damage to the post-synaptic membrane of the NMJ leading to damage and subsequent impaired synaptic transmission.4,6
ZILBRYSQ® is the first and only dual-acting small macrocyclic peptide C5 inhibitor.1,2
ZILBRYSQ® binds to C5 with high affinity and specificity, preventing its cleavage into C5a and C5b by C5 convertase.2,6
Additionally, by binding to the C5b moiety of C5, ZILBRYSQ® prevents its interaction with C6, blocking the formation of the MAC, should any C5b be formed.2
First small macrocyclic peptide C5 inhibitor for gMG2,7
As a peptide, ZILBRYSQ® can be used concomitantly with intravenous immunoglobulin (IVIg) or plasma exchange (PLEX) with no requirement for additional supplemental dosing.1,2
Abbreviations
Ab+, antibody positive; AChR, acetylcholine receptor; C[x], complement component [x]; gMG, generalised myasthenia gravis; IgG, immunoglobulin G; IVIg, intravenous immunoglobulin; MAC, membrane attack complex; NMJ, neuromuscular junction; PLEX, plasma exchange.
References
1. ZILBRYSQ® (zilucoplan) Product Information.
2. Howard JF, et al. Lancet Neurol. 2023;22(5):395–406.
3. Gable KL, et al. Front Immunol. 2020;10(3052)1-9.
4. Wolfe GI, et al. J Neurol Sci. 2021;430:118074.
5. Mané-Damas M, et al. Autoimmun Rev. 2022;21(7):103104.
6. Tang G, et al. Front Immunol. 2023;14:1–11.
7. Howard JF, et al. Ther Adv Neurol Disord. Published online April 17, 2024 doi:10.1177/17562864241243186.
PBS information: ZILBRYSQ is listed on the PBS as a section 100 item for the treatment of generalised Myasthenia Gravis (gMG). Refer to PBS Schedule for full authority information.
Please review the full Product Information before prescribing ZILBRYSQ®. The full Product Information is available from UCB Australia here.
▼ This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events at www.tga.gov.au/reporting-problems.
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors; ZILBRYSQ® is a complement inhibitor. Patients must be vaccinated against meningococcal infection (Neisseria meningitidis) and monitored for early signs of meningococcal infections. Refer to the boxed warning and section 4.4 Special Warnings and Precautions for Use in the approved product information (available at www.ucbpharma.com.au/zilbrysq) for additional guidance.
AU-ZL-2500001
Date of preparation: April 2026