Zilucoplan: A Novel Strategy for Management of Myasthenia Gravis

Background: Generalized myasthenia gravis is an autoimmune disease that leads to eventual end-organ damage. Zilucoplan is a new agent for the treatment of generalized myasthenia gravis for patients who are acetylcholine receptor antibody positive. Pharmacodynamics, And Pharmacokinetics: It is the first in its class that exerts its effect by binding to complement protein C5 and inhibiting activation to C5a and C5b-9. Zilucoplan may increase the risk of bacterial infections in patients, as its mechanism does heavily rely on altering components of the immune system. Zilucoplan has a black box warning because of the risk of meningococcal infections. Zilucoplan is the first subcutaneous, at-home treatment for generalized myasthenia gravis, which may allow for increased adherence. It is supplied as a prefilled syringe and the dosing varies based on the bodyweight. Onset of action was seen as early as 1 week in clinical studies. Clinical Trials: There were 2 major trials that led to Food and Drug Administration approval. A 12-week phase 2 study identified 0.3 mg/kg as the clinically efficacious dose for patients with generalized myasthenia gravis. A phase 3 trial (RAISE) showed clinical benefit in patients randomized to zilucoplan compared with placebo. There was a significant change in Myasthenia Gravis Activities of Daily Living score after 12 weeks of treatment. There was no difference in safety end points in both the phase 2 and phase 3 studies. Most patients experienced treatment-emergent adverse events, COVID-19 infections, and exacerbation of myasthenia gravis symptoms being among the most commonly reported. Therapeutic Advance: Zilucoplan is a new agent with a novel mechanism of action and provides an additional treatment option for patients who do not respond to standard of care. Evidence from postmarketing studies assessing the benefit–risk profile of zilucoplan in real-world settings, in addition to randomized controled trials, as well as pharmacoeconomic studies, is necessary to establish its place in therapy.