MECHANISMS OF ACTION

Targeting two distinct pathways for adults living with gMG

Actor Portrayals

Understand the mechanisms of FcRn- and C5-targeted therapies to help individualize care

gMG is caused by specific autoantibodies that impair transmission at the neuromuscular junction (NMJ)1,2

Acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) are key proteins essential to normal signal transduction2,3

Acetylcholine (ACh) binds to AChRs at the NMJ, initiating a cascade that ultimately signals muscle contraction2,3
MuSK contributes to the high-density clustering of AChRs at the NMJ, resulting in increased efficiency of signal transduction2,4

Most patients with gMG express pathogenic immunoglobulin G (IgG) autoantibodies that inhibit normal AChR or MuSK function1,5

Up to
95%

of patients with gMG present with either AChR or MuSK autoantibodies.6

85%
of patients

have pathogenic autoantibodies against AChR (AChR Ab+).6 These autoantibodies are IgG1 and IgG33

~5%-10%
of patients

have pathogenic autoantibodies against MuSK (MuSK Ab+).6 This autoantibody is IgG43

The pathophysiology of gMG differs based on which autoantibody is present1

AChR antibody-positive (Ab+) gMG

IgG1 and IgG3 autoantibodies damage the NMJ through mechanisms such as functional blockade of AChRs (a), cross-linking or internalization of AChRs (b), and complement activation (c).1,7

Graphic of the pathophysiology of anti-AChR antibody positive (Ab+) gMG.

Complement component 5 (C5) activation

C5 is a key protein involved in downstream complement activation, leading to the formation of the membrane attack complex (MAC), which results in NMJ destruction, AChR loss, and subsequent impaired synaptic transmission.1,7,8

Graphic of complement component 5 (C5) activation.

MuSK Ab+ gMG

IgG4 autoantibodies cause progressive loss of AChRs at the NMJ and, ultimately, synaptic failure by blocking activation of MuSK (d) and inhibiting AChR clustering (e), without engaging complement.1,5

Graphic of the pathophysiology of anti-MuSK antibody positive gMG.

Neonatal Fc receptor (FcRn) recycling

FcRn is part of a natural salvage mechanism that recycles autoantibodies back into circulation, preventing their degradation in the lysosome. By binding to AChR and MuSK IgG autoantibodies, FcRn allows their pathogenic effects to continue.9

Graphic of neonatal Fc receptor (FcRn) recycling.

Ab+, antibody positive; ACh, acetylcholine; AChR, acetylcholine receptor; C5, complement component 5; gMG, generalized myasthenia gravis; FcRn, neonatal Fc receptor; IgG, immunoglobulin G; MAC, membrane attack complex; MG, myasthenia gravis; MuSK, muscle-specific tyrosine kinase; NMJ, neuromuscular junction.

UCB is dedicated to providing options for providers to help personalize care for gMG—a chronic, unpredictable, neuromuscular autoimmune disease.10

Explore more about UCB's commitment to innovation in neurology and gMG.

Explore the RYSTIGGO
MOA (FcRn blocker) 
Explore the ZILBRYSQ
MOA (C5 inhibitor) 

References:

  1. Gilhus NE, Tzartos S, Evoli A, et al. Myasthenia gravis. Nat Rev Dis Primers. 2019;5(1):30. doi:10.1038/s41572-019-0079-y
  2. Albazli K, Kaminski HJ, Howard JF Jr. Complement inhibitor therapy for myasthenia gravis. Front Immunol. 2020;11:917. doi:10.3389/fimmu.2020.00917
  3. Huang K, Luo YB, Yang H. Autoimmune channelopathies at neuromuscular junction. Front Neurol. 2019;10:516. doi:10.3389/fneur.2019.00516
  4. Cao M, Koneczny I, Vincent A. Myasthenia gravis with antibodies against muscle specific kinase: an update on clinical features, pathophysiology and treatment. Front Mol Neurosci. 2020;13(159):1-13. doi:10.3389/fnmol.2020.00159
  5. Phillips WD, Vincent A. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms. F1000Res. 2016;5:F1000 Faculty Rev-1513. doi:10.12688/f1000research.8206.1
  6. Gambino CM, Agnello L, Ciaccio AM, et al. Detection of antibodies against the acetylcholine receptor in patients with myasthenia gravis: a comparison of two enzyme immunoassays and a fixed cell-based assay. J Clin Med. 2023;12(14):4781. doi:10.3390/jcm12144781
  7. Mantegazza R, Antozzi C. From traditional to targeted immunotherapy in myasthenia gravis: prospects for research. Front Neurol. 2020;11:981. doi:10.3389/fneur.2020.00981
  8. Noris M, Remuzzi G. Overview of complement activation and regulation. Semin Nephrol. 2013;33(6):479-492. doi:10.1016/j.semnephrol.2013.08.001
  9. Gable KL, Guptill JT. Antagonism of the neonatal Fc receptor as an emerging treatment for myasthenia gravis. Front Immunol. 2020;10:(3052):1-9. doi:10.3389/fimmu.2019.03052
  10. Bril V, Drużdż A, Grosskreutz J, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023;22(5):383-394. doi:10.1016/S1474-4422(23)00077-7

IMPORTANT SAFETY INFORMATION FOR RYSTIGGO (rozanolixizumab-noli)

RYSTIGGO is associated with important warnings and precautions, including increased risk of infection, drug-induced aseptic meningitis, and hypersensitivity reactions. The most common adverse reactions (≥10%) in patients with gMG are headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.

IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING FOR ZILBRYSQ (zilucoplan)

ZILBRYSQ, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for meningococcal bacteria at least 2 weeks prior to the first dose...

IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING FOR ZILBRYSQ (zilucoplan) Injection

INDICATION

ZILBRYSQ (zilucoplan) is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

ZILBRYSQ, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.

  • Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of ZILBRYSQ, unless the risks of delaying therapy outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccination against meningococcal bacteria in patients receiving a complement inhibitor.
  • Patients receiving ZILBRYSQ are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected.

Because of the risk of serious meningococcal infections, ZILBRYSQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ZILBRYSQ REMS.

CONTRAINDICATIONS

ZILBRYSQ is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.

WARNINGS AND PRECAUTIONS

Serious Meningococcal Infections

ZILBRYSQ, a complement inhibitor, increases a patient’s susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (septicemia and/or meningitis) in any serogroup, including non-groupable strains. Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of ZILBRYSQ treatment is contraindicated in patients with unresolved serious Neisseria meningitidis infection.

Complete or update meningococcal vaccination (for serogroups A, C, W, Y, and B) at least 2 weeks prior to administration of the first dose of ZILBRYSQ, according to current ACIP recommendations for patients receiving a complement inhibitor.

If urgent ZILBRYSQ therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer meningococcal vaccines as soon as possible.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Consider interruption of ZILBRYSQ in patients who are undergoing treatment for serious meningococcal infection, depending on the risks of interrupting treatment in the disease being treated.

ZILBRYSQ REMS

Due to the risk of serious meningococcal infections, ZILBRYSQ is available only through a restricted program under a REMS called ZILBRYSQ REMS.

Under the ZILBRYSQ REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risk of serious meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines. Additional information on the REMS requirements is available at www.ZILBRYSQREMS.com or 1-877-414-8353.

Other Infections

Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported in patients treated with complement inhibitors. ZILBRYSQ blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Administer vaccinations for the prevention of Streptococcus pneumoniae infection according to ACIP recommendations. Patients receiving ZILBRYSQ are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination.

Pancreatitis and Other Pancreatic Conditions

Pancreatitis and pancreatic cysts have been reported in patients treated with ZILBRYSQ. Patients should be informed of this risk before starting ZILBRYSQ. Obtain lipase and amylase levels at baseline before starting treatment with ZILBRYSQ. Discontinue ZILBRYSQ in patients with suspected pancreatitis and initiate appropriate management until pancreatitis is ruled out or has resolved.

ADVERSE REACTIONS

In a placebo-controlled study, the most common adverse reactions (reported in at least 10% of gMG patients treated with ZILBRYSQ) were injection site reactions, upper respiratory tract infections, and diarrhea.

Please see the full Prescribing Information.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR RYSTIGGO (rozanolixizumab-noli)

INDICATION

RYSTIGGO (rozanolixizumab-noli) is indicated 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.

WARNINGS AND PRECAUTIONS

Infections: RYSTIGGO may increase the risk of infection. Delay RYSTIGGO administration in patients with an active infection until the infection is resolved. During treatment with RYSTIGGO, monitor for clinical signs and symptoms of infection. If serious infection occurs, administer appropriate treatment and consider withholding RYSTIGGO until the infection has resolved.

Immunization

Immunization with vaccines during RYSTIGGO treatment has not been studied. The safety of immunization with live or live-attenuated vaccines and the response to immunization with any vaccine are unknown. Because RYSTIGGO causes a reduction in IgG levels, vaccination with live-attenuated or live vaccines is not recommended during treatment with RYSTIGGO. Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with RYSTIGGO.

Aseptic Meningitis: Serious adverse reactions of aseptic meningitis (also called drug-induced aseptic meningitis) have been reported in patients treated with RYSTIGGO. If symptoms consistent with aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care.

Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema and rash, were observed in patients treated with RYSTIGGO. Management of hypersensitivity reactions depends on the type and severity of the reaction. Monitor patients during treatment with RYSTIGGO and for 15 minutes after for clinical signs and symptoms of hypersensitivity reactions. If a reaction occurs, institute appropriate measures if needed.

ADVERSE REACTIONS

In a placebo-controlled study, the most common adverse reactions (reported in at least 10% of RYSTIGGO-treated patients) were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea. Serious infections were reported in 4% of patients treated with RYSTIGGO. Three fatal cases of pneumonia were identified, caused by COVID-19 infection in two patients and an unknown pathogen in one patient. Six cases of infections led to discontinuation of RYSTIGGO.

Please see the full Prescribing Information.

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RYSTIGGO® and ZILBRYSQ® are registered trademarks of the UCB Group of Companies. All other trademarks and registered trademarks are the property of their respective holders. 

©2026 UCB, Inc., Smyrna, GA 30080. All rights reserved.

US-RZ-2500510

UCB respects your privacy. Click here to manage your email preferences.

For US Healthcare Professionals Only.

RYSTIGGO® and ZILBRYSQ® are registered trademarks of the UCB Group of Companies. All other trademarks and registered trademarks are the property of their respective holders.

©2026 UCB, Inc., Smyrna, GA 30080. All rights reserved.

 

US-RZ-2500510