Introduction
Zilbrysq (zilucoplan) is a complement inhibitor indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. It represents a novel therapeutic approach in the management of this autoimmune neuromuscular disorder.
Mechanism of Action
Zilucoplan is a macrocyclic peptide that inhibits the complement component 5 (C5) protein, preventing the formation of the membrane attack complex (MAC), which is implicated in the destruction of the neuromuscular junction in myasthenia gravis. By blocking C5 cleavage into C5a and C5b, it prevents the terminal complement cascade activation that contributes to the pathophysiology of gMG.
Indications
Zilbrysq is approved for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.
Dosage and Administration
- Recommended dosage: 0.3 mg/kg once daily
- Route of administration: Subcutaneous injection
- Special populations: No dosage adjustment required for renal or hepatic impairment
- Administration instructions: Administer subcutaneously in the abdomen, thigh, or upper arm. Rotate injection sites.
Pharmacokinetics
- Absorption: Peak plasma concentrations achieved approximately 2 hours after subcutaneous administration
- Distribution: Volume of distribution: 0.1 L/kg
- Metabolism: Not metabolized by cytochrome P450 enzymes
- Elimination: Primarily excreted unchanged in urine with a half-life of approximately 8 hours
Contraindications
- Known hypersensitivity to zilucoplan or any component of the formulation
- Patients with unresolved Neisseria meningitidis infection
Warnings and Precautions
- Meningococcal infections: Zilbrysq increases the risk of serious infections caused by Neisseria meningitidis. Vaccinate or revaccinate according to current guidelines at least 2 weeks prior to initiating Zilbrysq unless the risks of delaying therapy outweigh the risks of developing a meningococcal infection.
- Monitor for signs and symptoms of meningococcal infection and treat immediately if infection is suspected.
Drug Interactions
- No formal drug interaction studies have been conducted.
- Based on its pharmacokinetic profile, no clinically significant interactions are expected with drugs metabolized by CYP enzymes.
Adverse Effects
- Most common adverse reactions (≥10%): Injection site reactions, upper respiratory tract infection, headache, oropharyngeal pain
- Serious adverse reactions: Meningococcal infection
Monitoring Parameters
- Monitor for signs and symptoms of meningococcal infection
- Monitor for injection site reactions
- Monitor for signs of myasthenia gravis exacerbation
- Monitor for signs of hypersensitivity reactions
Patient Education
- Educate patients about the risk of meningococcal infection and the need for vaccination
- Instruct patients to seek immediate medical attention for signs of meningococcal infection
- Instruct patients on proper injection technique and rotation of injection sites
- Inform patients about the importance of reporting any signs of infection or injection site reactions
References
1. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 3. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 4. Howard JF, et al. Safety and: Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, 5. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 6. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 7. Howard JF, et al. Safety and efficacy of zilucoplan in generalized my 8. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 9. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 10. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 11. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 12. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 13. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 14. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 15. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 16. Howard JF, 17. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 18. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 19. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 20. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 21. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 22. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 23. Howard JF, et al. Safety and efficacy of z 24. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 25. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placebo-controlled, multicentre, phase 2, randomised, double-blind, placeholder 26. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 27. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 28. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 29. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 30. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 31. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 32. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 33. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 34. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 35. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 36. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 37. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 38. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 39. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 40. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 41. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 42. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 43. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 44. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 45. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 46. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 47. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 48. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 49. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, 50. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 51. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind, placeholder 52. Howard JF, et al. Safety and efficacy of zilucoplan in generalized myasthenia gravis: A phase 2, randomised, double-blind