CurrentCignaPolicy IP0622

Complement Inhibitors – Zilbrysq - (IP0622)

Defines Cigna coverage and prior authorization criteria for Zilbrysq (zilucoplan subcutaneous injection) for treatment of anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG) in adults, including initial and continuation therapy criteria, not-covered uses, prescribing specialist requirement, documentation expectations, and applicable HCPCS codes.

Policy Summary

PayerCigna

PolicyComplement Inhibitors – Zilbrysq - (IP0622)

Policy CodePolicy IP0622

Change TypeSelected revision (coding added); documentation updates; examples updated

Effective Date

Next Review Date

Key ActionPrior Authorization is required for Zilbrysq; approvals provided for specified durations (6 months initial, 1 year continuation).

SourceLink

POLICY UPDATE CHANGES

Added coding table with HCPCS codes C9399 and J3490.

Updated documentation statement to require prescription receipts and patient-specific identifying information.

Expanded 'Conditions Not Covered' to include Uplizna (inebilizumab-cdon) and added Imaavy to examples of neonatal Fc receptor blockers.

Policy created as new on 07/01/2024 and had subsequent annual revisions with 'No criteria changes' on 03/01/2025 and 03/01/2026.

6mo;1yrApproval Durations (initial; continuation)

≥18Age eligibility (years minimum)

Coverage Summary

Scope: Defines Cigna coverage and prior authorization criteria for Zilbrysq (zilucoplan subcutaneous injection) for treatment of anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG) in adults, including initial and continuation therapy criteria, not-covered uses, prescribing specialist requirement, documentation expectations, and applicable HCPCS codes. Coverage stance: covered_with_criteria. Indication summary: Zilbrysq is indicated for adults with anti-acetylcholine receptor antibody-positive gMG. Safety: there is a Boxed Warning for serious meningococcal infections and Zilbrysq is available only through a restricted access REMS program.

Initial and Continuation Therapy Criteria

FDA-Approved Indication - Generalized Myasthenia Gravis

Approve for the duration noted if the patient meets ONE of the following (A or B):

ANY of the following

A) Initial therapy (Approve for 6 months)
- Patient is ≥ 18 years of age≥ 18 years
- Patient has confirmed anti-acetylcholine receptor antibody-positive generalized myasthenia gravis
  [documentation required]
- Disease severity and activity
  - Myasthenia Gravis Foundation of America classification of II to IV
  - Myasthenia Gravis Activities of Daily Living (MG-ADL) score of ≥ 6MG-ADL ≥ 6
- Pyridostigmine use or intolerance
  - Patient received or is currently receiving pyridostigmine
  - Patient has had inadequate efficacy, a contraindication, or significant intolerance to pyridostigmine
- Immunosuppressant therapy history
  - Patient received or is currently receiving two different immunosuppressant therapies for ≥ 1 year≥ 2 therapies for ≥ 1 year
    Examples: azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, tacrolimus, cyclophosphamide.
  - Patient had inadequate efficacy, a contraindication, or significant intolerance to two different immunosuppressant therapies2 therapies
    Examples: azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, tacrolimus, cyclophosphamide.
- Patient has evidence of unresolved symptoms of generalized myasthenia gravis
  Examples include difficulty swallowing, difficulty breathing, and functional disability resulting in discontinuation of physical activity (e.g., double vision, talking, impairment of mobility).
- Medication is being prescribed by or in consultation with a neurologist
B) Patient is currently receiving Zilbrysq (Approve for 1 year)
- Patient is ≥ 18 years of age≥ 18 years
- According to the prescriber, patient is continuing to derive benefit from Zilbrysq
  Examples of derived benefit include reductions in exacerbations of myasthenia gravis; improvements in speech, swallowing, mobility, and respiratory function.
- Medication is being prescribed by or in consultation with a neurologist

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Conditions Not Covered (Not Medically Necessary)

Zilbrysq for any other use is considered not medically necessary, including the following examples:

Concomitant use with another complement inhibitor, a neonatal Fc receptor blocker, a rituximab product, or Uplizna (inebilizumab-cdon intravenous infusion) is not covered

Examples of complement inhibitors: eculizumab (Soliris, biosimilars) and Ultomiris (ravulizumab-cwvz). Examples of neonatal Fc receptor blockers: Imaavy (nipocalimab-aahu), Rystiggo (rozanolixizumab-noli), Vyvgart (efgartigimod alfa), Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc).

Applicable Codes

Covered HCPCS/Drug Codes (when criteria met)HCPCSCovered

C9399	Unclassified drugs or biologicals
J3490	Unclassified drugs

Provider Actions

Prior Authorization

Prior authorization required

Prior authorization is required for benefit coverage of Zilbrysq. Approvals are provided for the durations specified in the policy: 6 months for initial therapy and 1 year for continuation therapy.

C9399
J3490

Documentation Required

Documentation requirements

Documentation is required where noted in the criteria, including confirmation of anti-acetylcholine receptor antibody positivity, prior therapies (e.g., pyridostigmine and immunosuppressants), MGFA class, MG-ADL score, and evidence of unresolved symptoms. Documentation may include chart notes, laboratory tests, claims records, and prescription receipts and must include patient-specific identifying information.

Clinical Evidence

-4.39 vs -2.30 (P < 0.001)MG-ADL change at Week 12

RAISE study, phase 3, n=174Key trial

Evidence summary: A 12-week randomized, double-blind, placebo-controlled trial (RAISE; n=174) in anti-acetylcholine receptor antibody-positive gMG patients demonstrated statistically significant improvement in MG-ADL with Zilbrysq versus placebo (-4.39 vs -2.30 points; P < 0.001). Safety context: Zilbrysq carries a Boxed Warning for serious meningococcal infections and is available only through the Zilbrysq REMS restricted access program.

Background & Definitions

Background: Zilbrysq (zilucoplan) is a complement C5 inhibitor indicated for adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. It has a Boxed Warning for serious meningococcal infections and is available only through the REMS restricted access program. Coding: applicable HCPCS codes include C9399 and J3490 when policy criteria are met.

Term	Definition
MG-ADL	Myasthenia Gravis-Activities of Daily Living, an 8-item scale assessing daily function; higher score indicates greater impairment.
MGFA	Myasthenia Gravis Foundation of America clinical classification system.

Revision History

07/01/2024policy_created

Initial policy created as new on 07/01/2024.

03/01/2025annual_revision

Annual revision on 03/01/2025 with no criteria changes.

08/15/2025selected_revision

Selected revisions began 08/15/2025 updating examples and Conditions Not Covered; Imaavy was later added to examples of neonatal Fc receptor blockers (part of multi-step revisions between 08/15/2025 and 10/01/2025).