Zilucoplan: a novel therapeutic approach to treat generalized myasthenia gravis


  • Fatima Laique Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
  • Sameen Mukhtar Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
  • Mubashir Mohiuddin Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan




MG/gMG, NMJ, Complement, Acetylcholine receptor, Zilucoplan


Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by muscle weakness due to autoantibodies targeting the neuromuscular junction (NMJ). Zilucoplan, a novel complement inhibitor, has shown promise in managing generalized MG (gMG) by blocking the terminal complement cascade. This article provides an overview of Zilucoplan's pharmacological properties, including its mechanism of action, pharmacokinetics, and pharmacodynamics. Clinical trials, including a phase 3 trial (RAISE), have demonstrated Zilucoplan's efficacy in improving muscle strength and function, as measured by the MG-ADL (MG-activities of daily life) score, compared to placebo. The safety profile of Zilucoplan is favorable, with injection-site reactions being the most common adverse event. Notably, Zilucoplan effectively inhibits both wild-type and clinical C5 variants, expanding its potential utility for patients who do not respond well to existing treatments. While further research is needed to assess its long-term safety and efficacy, Zilucoplan represents a valuable addition to the therapeutic armamentarium for managing gMG.


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Myasthenia gravis. Johns Hopkins Medicine. 2023. Available at: https://www.hopkinsmedicine.org/ health/conditions-and-diseases/myasthenia-gravis#:~:text=Myasthenia%20gravis%20(MG)%20is%20a,%2C%20mouth%2C%20throat%20and%20limbs. Accessed on 12 January, 2024.

Fana AKSM Faan. Myasthenia gravis: Practice Essentials, background, anatomy. Available at: https://emedicine.medscape.com/article/1171206-overview. Accessed on 12 January, 2024.

Professional CCM. Myasthenia gravis (MG). Cleveland Clinic. Available at: https://my. clevelandclinic.org/health/diseases/17252-myasthenia-gravis-mg. Accessed on 12 January, 2024.

Jackson K, Parthan A, Lauher-Charest M, Broderick L, Law N, Barnett C. Understanding the Symptom Burden and Impact of Myasthenia Gravis from the Patient's Perspective: A Qualitative Study. Neurol Ther. 2023;12(1):107-28.

Katella K. Myasthenia gravis: New drugs and a road to individualized treatment. Yale Medicine. 2023. Available at: https://www.yalemedicine.org/news/ myasthenia-gravis-new-drugs-individualized-treatment#:~:text=Zilucoplan%20(brand%20name%20ZILBRYSQ%C2%AE,damage%20to%20the%20neuromuscular%20junction. Accessed on 12 January, 2024.

Myasthenia gravis. National Institute of Neurological Disorders and Stroke. Available at: https://www.ninds.nih.gov/health-information/ disorders/myasthenia-gravis. Accessed on 12 January, 2024.

Shirley M. Zilucoplan: First Approval. Drugs. 2024;84(1):99-104.

Tang GQ, Tang Y, Dhamnaskar K, Hoarty MD, Vyasamneni R, Vadysirisack DD, et al. Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation. Front Immunol. 2023;14:1213920.

Howard JF Jr, Vissing J, Gilhus NE, Leite MI, Utsugisawa K, Duda PW, et al. Zilucoplan: An Investigational Complement C5 Inhibitor for the Treatment of Acetylcholine Receptor Autoantibody-Positive Generalized Myasthenia Gravis. Expert Opin Investig Drugs. 2021;30(5):483-93.

Zilucoplan: Uses, interactions, mechanism of action | DrugBank Online. DrugBank. Available at: https://go.drugbank.com/drugs/DB15636. Accessed on 12 January, 2024.

Tüzün E, Huda R, Christadoss P. Complement and cytokine based therapeutic strategies in myasthenia gravis. J Autoimmun. 2011;37(2):136-43.

Allenbach Y, Arouche-Delaperche L, Preusse C, Radbruch H, Butler-Browne G, Champtiaux N, et al. Necrosis in anti-SRP+ and anti-HMGCR+myopathies: Role of autoantibodies and complement. Neurology. 2018;90(6):e507-17.

Menon D, Bril V. Pharmacotherapy of Generalized Myasthenia Gravis with Special Emphasis on Newer Biologicals. Drugs. 2022;82(8):865-87.

Engel AG, Lindstrom JM, Lambert EH, Lennon VA. Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model. Neurology. 1977;27(4):307-15.

Johnston J, Ricardo A, Arata M. A phase 1 multiple-dose clinical study of RA101495, a subcutaneously administered synthetic macrolytic peptide inhibitor of complement C5 for treatment of paroxysmal noctural hemogloginuria. Haematologica. 2016;101:415-6.

Zilbrysq Interactions Checker. Drugs.com. Available at: https://www.drugs.com/drug-interactions/ zilucoplan,zilbrysq.html. Accessed on 12 January, 2024.

Johnston J, Ricardo A, Arata M, Lickliter J, DeMarco SJ, Fahrner R, et al. A phase 1 single-ascending-dose clinical study of RA101495, a subcutaneously administered synthetic macrocyclic peptide inhibitor of complement C5 for treatment of paroxysmal nocturnal hemoglobinuria [abstract P632]. Haematologica. 2016;101:247-8.

Inglis JE, Radziwon KA, Maniero GD. The serum complement system: a simplified laboratory exercise to measure the activity of an important immune system component. Adv Physiol Educ. 2008;32(4):317-21.

Zilbrysq (zilucoplan) dosing, indications, interactions, adverse effects, and more. Available at: https://reference.medscape.com/drug/zilbrysq-zilucoplan-4000353#4. Accessed on 12 January, 2024.

Howard JF Jr, Bresch S, Genge A, Hewamadduma C, Hinton J, Hussain Y, et al. Safety and efficacy of zilucoplan in patients with generalized myasthenia gravis (RAISE): a randomized, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22(5):395-406.






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