CurrentCignaPolicy IP0622

Complement Inhibitors - Zilbrysq

Defines Cigna coverage, prior authorization, and medical necessity criteria for Zilbrysq (zilucoplan subcutaneous injection) for adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

Policy Summary

PayerCigna

PolicyComplement Inhibitors - Zilbrysq

Policy CodePolicy IP0622

Change TypeCoding additionsdocumentation and coverage clarifications

Effective Date

Next Review Date

Key ActionObtain prior authorization; approvals are for initial therapy 6 months and continuation 1 year when criteria are met.

SourceLink

POLICY UPDATE CHANGES

Coding table with HCPCS codes C9399 and J3490 was added.

Documentation statement was updated to require prescription receipts and explicit patient-specific identifying information.

Conditions Not Covered was expanded to explicitly include concomitant use with Uplizna (inebilizumab-cdon intravenous infusion).

≥18minimum age for coverage

MG-ADL ≥6baseline symptom severity

6 monthsduration for new starts

1 yearduration for ongoing therapy

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Boxed WarningREMS / boxed warning

Coverage criteria for Zilbrysq (zilucoplan)

inv-03: Conditions Not Covered

Not medically necessary uses: Use of Zilbrysq for any indication other than anti‑AChR antibody-positive generalized myasthenia gravis in adults is considered not medically necessary

Concomitant therapy exclusion: Concomitant use with another complement inhibitor, a neonatal Fc receptor blocker, a rituximab product, or Uplizna (inebilizumab-cdon) is considered not medically necessary

Examples of complement inhibitors: eculizumab (Soliris) and ravulizumab (Ultomiris); examples of neonatal Fc receptor blockers: Imaavy (nipocalimab), rozanolixizumab, efgartigimod products (Vyvgart, Vyvgart Hytrulo)

Concomitant use of Zilbrysq with another complement inhibitor, a neonatal Fc receptor blocker, a rituximab product, or Uplizna (inebilizumab-cdon) is explicitly considered not medically necessary. The policy notes there is no evidence to support concurrent use and gives examples of complement inhibitors (e.g., eculizumab [Soliris] and ravulizumab [Ultomiris]) and neonatal Fc receptor blockers (e.g., nipocalimab [Imaavy], rozanolixizumab, and efgartigimod products [Vyvgart, Vyvgart Hytrulo]).

Use of Zilbrysq for any indication other than the FDA‑approved indication—adult anti‑acetylcholine receptor (anti‑AChR) antibody‑positive generalized myasthenia gravis—is considered not medically necessary. The policy’s Conditions Not Covered section states that Zilbrysq for any other use is not medically necessary and will be updated as new data become available.

Billing and coding

Considered Medically Necessary when criteria metHCPCSCovered

C9399	Unclassified drugs or biologicals.
J3490	Unclassified drugs.

inv-07: MG-ADL score — ≥ 6

MG-ADL thresholdMG-ADL score ≥ 6

Scale descriptionAn 8-item patient-reported scale assessing daily functions affected by generalized myasthenia gravis

Scoring directionHigher scores indicate greater impairment

Clinical use in policyRequired baseline severity for initial therapy eligibility

What providers must do

Prior Authorization

Prior Authorization Required

Prior authorization is required for benefit coverage of Zilbrysq. Approvals are provided for the durations noted in the policy (initial approvals = 6 months; continuation/renewal approvals = 1 year). When approvals are authorized in months, 1 month = 30 days. Zilbrysq must be prescribed by or in consultation with a physician who specializes in the condition being treated (e.g., a neurologist).

Initial approval duration: 6 months when initial therapy criteria are met
Continuation approval duration: 1 year when continuation criteria are met
Approvals measured in months: 1 month = 30 days
Prescriber requirement: prescribed by or in consultation with a specialist (neurologist)

Prior Authorization

Provider Actions Before Initial Approval

Before approval for initial therapy, the patient must have received or be currently receiving pyridostigmine, OR have documented inadequate efficacy, a contraindication, or significant intolerance to pyridostigmine. The prescriber must document anti-acetylcholine receptor antibody–positive status and relevant disease severity measures (MGFA class II–IV and MG-ADL ≥ 6) as specified in the criteria.

Clinical background

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease characterized by activity‑dependent skeletal muscle weakness, most commonly caused by antibodies to the acetylcholine receptor. Zilbrysq (zilucoplan) is an FDA‑approved complement C5 inhibitor indicated specifically for adults with anti‑AChR antibody‑positive generalized MG. Clinical trials demonstrated statistically significant improvement in MG‑related function (including MG‑ADL scores) versus placebo over 12 weeks, supporting its use in patients meeting the policy’s severity and treatment‑history thresholds.

Scales and classifications

inv-13: MG-ADL definition — Myasthenia Gravis-Activities of Daily Living: an 8-item scale; higher scores indicate greater impairment

NameMyasthenia Gravis-Activities of Daily Living (MG-ADL)

Item count8 items

AssessmentAssesses impact of generalized MG on daily functions (eight signs or symptoms)

ScoringEach item scored on a 4-point scale; higher total indicates greater impairment

Trial useUsed as primary efficacy measure in Zilbrysq RCT (baseline inclusion: MG-ADL ≥ 6)

inv-14: MGFA classification — Myasthenia Gravis Foundation of America clinical classification (classes II to IV used here)

Policy Summary

PayerCigna

PolicyComplement Inhibitors - Zilbrysq

Policy CodePolicy IP0622

Change TypeCoding additionsdocumentation and coverage clarifications

Effective Date

Next Review Date

Key ActionObtain prior authorization; approvals are for initial therapy 6 months and continuation 1 year when criteria are met.

SourceLink

On This Page

Patient received or is currently receiving pyridostigmine; OR documented inadequate efficacy, contraindication, or significant intolerance to pyridostigmine
Documented anti-acetylcholine receptor antibody–positive generalized myasthenia gravis [documentation required]
Disease severity: MGFA class II–IV and MG-ADL score ≥ 6

Documentation Required

Documentation Requirements

Documentation is required where noted in the criteria. Acceptable documentation may include chart notes, laboratory test results, claims records, prescription receipts, and other supporting information. All documentation must include patient-specific identifying information and should be available for review at the time of the prior authorization request.

Examples: chart notes, laboratory tests, claims records, prescription receipts, identifiers
All documentation must include patient-specific identifying information
Provide documentation for antibody status, prior therapies, MGFA class, MG-ADL score, and evidence of ongoing benefit for continuation requests

Denial Risk

Billing and Denial Risks

Requests for Zilbrysq submitted without prior authorization, or claims billed without covered HCPCS/administration codes for the medication, may be denied. Use of Zilbrysq for indications other than FDA-approved generalized myasthenia gravis (or as specified in this policy) may be considered not medically necessary and denied.

Requests lacking prior authorization may be denied
Claims billed without appropriate covered HCPCS/J-codes (e.g., C9399, J3490 as applicable) or other required coding may be denied
Use for indications outside the policy (including concomitant use with another complement inhibitor, neonatal Fc receptor blocker, rituximab product, or Uplizna®) may be denied as not medically necessary

Myasthenia Gravis Foundation of America (MGFA) clinical classification

Classes referencedClasses II to IV are used for eligibility in this policy

Clinical contextMGFA classification denotes severity and distribution of muscle involvement

Policy roleRequired as part of initial therapy criteria alongside MG-ADL ≥ 6