ZILUCOPLAN INJ,SOLN

Clinical Criteria Summary

Generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor antibody positive (AChR+)
No evidence to support use in MuSK+, LRP4+, or seronegative disease

Once daily subcutaneous (SubQ) injection
Weight-based dosing: <56 kg = 16.6 mg; ≥56 kg to <77 kg = 23 mg; ≥77 kg = 32.4 mg
Can be self-administered

REMS program required to reduce risk of meningococcal infections
Meningococcal vaccination must be completed at least 2 weeks prior to administering the first dose
Monitor for early signs of meningococcal infection; evaluate immediately if infection is suspected
Contraindicated in patients with unresolved Neisseria meningitidis infection
Increased susceptibility to infections, particularly encapsulated bacteria; vaccination for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae recommended
Obtain lipase and amylase levels at baseline; discontinue if pancreatitis is suspected until ruled out

Effective as a steroid-sparing treatment option for AChR+ gMG
May be considered as add-on therapy when traditional oral immunosuppressants (azathioprine, mycophenolate, steroids) with or without acetylcholinesterase inhibitor (pyridostigmine) are ineffective
Not studied as chronic immunotherapy in combination with plasma exchange, intravenous immunoglobulin (IVIg), rituximab, neonatal Fc receptor antagonists, or other complement inhibitors

Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Thymectomy within 12 months
Concomitant therapy with neonatal Fc receptor antagonists (e.g., efgartigimod), rituximab, or other complement inhibitors (e.g., eculizumab, ravulizumab)
Chronic therapy with intravenous immunoglobulin or plasma exchange (may be used for exacerbations)

Care provided by a VA/VA Community Care neurologist
Diagnosis of acetylcholine receptor (AChR) antibody positive generalized myasthenia gravis (gMG)
Not a candidate for thymectomy
Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV
Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) total score ≥ 6
Vaccination against pneumococcal disease and Neisseria meningitidis with both Meningococcal conjugate vaccine (MenACWY) and Meningococcal serogroup B vaccine

One of the following must be met:
Inadequate symptom control to maximally tolerated pyridostigmine and at least two immunosuppressive agents separately trialed for at least 6 months each (e.g., azathioprine, cyclosporine, mycophenolate)
History of intolerance or contraindication preventing trial of immunosuppressive agents (e.g., azathioprine, cyclosporine, mycophenolate)
Lack of symptom control despite 4 or more courses of plasma exchange, high-dose steroid bursts and/or intravenous immune globulin within a 12-month period

In emergent cases where waiting to initiate zilucoplan at least two weeks after completion of vaccination is not possible, patients should begin the vaccination series at the time of initial zilucoplan dosing and be provided with appropriate prophylaxis.