ModifiedCentenePolicy CP PHAR.616

Clinical Policy: Zilucoplan (Zilbrysq)

Covers medical necessity criteria, dosing, and continuation requirements for zilucoplan (Zilbrysq) for treatment of anti‑AChR antibody positive generalized myasthenia gravis in adults for Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyClinical Policy: Zilucoplan (Zilbrysq)

Policy CodePolicy CP PHAR.616

Change TypeFDA labeling updatesconcurrent-therapy contraindications added

Effective Date10.17.23

Next Review Date

Key ActionSubmit prior authorization with documentation of adult gMG diagnosis, positive anti‑AChR antibodies, MG-ADL ≥6 baseline, prior therapy history, prescriber specialty, and current weight.

SourceLink

POLICY UPDATE CHANGES

Drug is now FDA approved and dosing criteria updated per FDA labeling.

Added Bkemv, Epysqli, and Rystiggo to the list of therapies that Zilbrysq should not be prescribed concurrently with.

Drug is now FDA approved and dosing criteria were updated per FDA labeling.

Adults, anti‑AChR+FDA approved population

≥6Baseline MG-ADL required

6 moContinuation approval

REMS: meningococcal vaxSafety requirement

Policy Summary

PayerCentene

PolicyClinical Policy: Zilucoplan (Zilbrysq)

Policy CodePolicy CP PHAR.616

Change TypeFDA labeling updatesconcurrent-therapy contraindications added

Effective Date10.17.23

Next Review Date

Key ActionSubmit prior authorization with documentation of adult gMG diagnosis, positive anti‑AChR antibodies, MG-ADL ≥6 baseline, prior therapy history, prescriber specialty, and current weight.

SourceLink

On This Page

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Weight-tieredPrefilled syringes

Coverage Criteria

inv-01: Initial Approval

Covered when ALL of the following are met:

Initial Approval Criteria: 1. Diagnosis of generalized myasthenia gravis (gMG).

Initial Approval Criteria: 2. Prescribed by or in consultation with a neurologist.

Initial Approval Criteria: 3. Age > 18 years.

Initial Approval Criteria: 4. Baseline Myasthenia Gravis–Activities of Daily Living (MG‑ADL) total score ≥ 6.≥ 6

Initial Approval Criteria: 5. Myasthenia Gravis Foundation of America (MGFA) clinical classification Class II–IV.

Initial Approval Criteria: 6. Positive serologic test for anti‑acetylcholine receptor (anti‑AChR) antibodies.

Initial Approval Criteria: 7. Failure of a corticosteroid (see Appendix B) unless contraindicated or clinically significant adverse effects are experienced.

Initial Approval Criteria: 8. Failure of a cholinesterase inhibitor (see Appendix B) unless contraindicated or clinically significant adverse effects are experienced.

Initial Approval Criteria: 9. Failure of at least one immunosuppressive therapy (see Appendix B) unless contraindicated or clinically significant adverse effects are experienced.

Initial Approval Criteria: 10. Not prescribed concurrently with Soliris, Bkemv, Epysqli, Ultomiris, Rystiggo, or Vyvgart.

Initial Approval Criteria: 11. Documentation of member's current weight in kilograms.

Initial Approval Criteria: 12. Requested dose does not exceed weight‑tiered dosing limits and product use: one prefilled syringe per day.

Dose tiers: weight < 56 kg = 16.6 mg/day; 56–<77 kg = 23 mg/day; ≥77 kg = 32.4 mg/day; 1 prefilled syringe daily.

inv-02: Continuation (Renewal) Criteria

Covered when ALL of the following are met:

Continuation Criteria: 1. Member is currently receiving medication via the Centene benefit or has previously met initial approval criteria (continuity of care provisions apply where state/product rules require).

Continuation Criteria: 2. Member demonstrates positive clinical response defined as ≥ 2‑point reduction from baseline in MG‑ADL total score.≥ 2‑point reduction from baseline

Continuation Criteria: 3. Documentation of member's current weight in kilograms.

Continuation Criteria: 4. Not prescribed concurrently with Soliris, Bkemv, Epysqli, Ultomiris, Rystiggo, or Vyvgart.

Non‑FDA approved indications for zilucoplan (Zilbrysq) are excluded from coverage under this policy unless the request includes sufficient clinical documentation of efficacy and safety in accordance with the applicable off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid) or the member’s evidence of coverage allows coverage for the requested indication.

Zilucoplan (Zilbrysq) is contraindicated in patients with an unresolved Neisseria meningitidis infection. The product carries boxed warning(s) for serious meningococcal infections and therapy should not be initiated while such an infection is present.

Concurrent prescribing restrictions were updated during the 1Q 2025 annual review: Bkemv, Epysqli, and Rystiggo were added to the list of therapies that should not be prescribed concurrently with Zilbrysq. Prior authorization and prescribing checks must reflect these additions.

Requests for off‑label use of Zilbrysq for indications not addressed in this policy must follow the referenced off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53). Use for non‑FDA approved indications without sufficient supporting documentation per those policies is not authorized.

Coding & Measurement Requirements

MG-ADL baseline requirement

MG-ADL baseline required for initial approvalMG-ADL score ≥ 6 at baseline

Applies toAdults (age > 18 years) with diagnosis of generalized myasthenia gravis (gMG)

Documentation neededProvider must document baseline MG-ADL score in chart notes or submitted clinical records

Clinical response threshold for continuation

Clinical response required for continuationDemonstrates a ≥ 2-point reduction from baseline in total MG-ADL score

Other continuation requirementsMember currently receiving medication via Centene benefit or previously met initial criteria; documentation of current weight in kg

Provider Actions & Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required. Zilbrysq (zilucoplan) will be authorized only when all specified clinical criteria are met and required documentation is submitted to support the request. Coverage decisions remain subject to the member's contract, evidence of coverage, and applicable state/federal requirements.

Prior authorization must document an adult (age > 18 years) diagnosis of generalized myasthenia gravis (gMG).
Prescribing or consult must be by a neurologist.
Member must have a positive serologic test for anti‑AChR antibodies.
Baseline MG‑ADL score ≥ 6 and MGFA clinical classification Class II–IV.
Therapeutic trial history: failure, contraindication, or intolerance to a cholinesterase inhibitor AND a corticosteroid AND at least one immunosuppressant (see Appendix B for examples).
Zilbrysq must not be prescribed concurrently with eculizumab products (e.g., Soliris, Ultomiris) or specified complement inhibitors added to labeling (e.g., Bkemv, Epysqli, Rystiggo, Vyvgart) per updated labeling — prior authorization will reflect such concurrent therapy restrictions.
Dosing limits and weight‑based dosing must be followed as specified in the policy (weight documented in kg).
REMS requirement: Zilbrysq is available only through a REMS program due to risk of life‑threatening meningococcal infection. Patients should be vaccinated with a meningococcal vaccine at least 2 weeks prior to the first dose when possible and revaccinated per current guidelines; absence of vaccination or unresolved Neisseria meningitidis infection may preclude therapy.

Background

Zilucoplan (Zilbrysq) is a complement inhibitor approved for treatment of generalized myasthenia gravis in adults who are anti‑AChR antibody positive. The policy was created pre‑emptively and updated when the drug received FDA approval and dosing guidance; the 1Q 2025 review added specific concurrent‑therapy contraindications (Bkemv, Epysqli, Rystiggo). Therapy requires adherence to REMS safety measures related to meningococcal risk and applicable off‑label policies for any non‑FDA indications.

Definitions

Definition of MG‑ADL

InstrumentMG-ADL is an 8-item patient-reported scale measuring functional status in 8 domains (talking, chewing, swallowing, breathing, ability to brush teeth/comb hair, arise from a chair, double vision, eyelid droop)

ScoringEach domain scored 0–3 (0 = normal, 3 = most severe), total score is sum of items

Clinically meaningful changeA 2-point decrease in MG-ADL total score is considered a clinically meaningful response

Definition of gMG

TermgMG stands for generalized myasthenia gravis

ContextgMG denotes myasthenia gravis with generalized (rather than purely ocular) muscle involvement as used in this policy

Continuation Criteria: 5. If a dose increase is requested, the new dose does not exceed the weight‑tiered dosing limits and product use: one prefilled syringe per day.

Dose tiers: weight < 56 kg = 16.6 mg/day; 56–<77 kg = 23 mg/day; ≥77 kg = 32.4 mg/day; Approval duration for continuation: 6 months.

Approval duration for continuationApproval duration: 6 months

Required documentation: office chart notes, labs (including anti‑AChR serology), MG‑ADL and MGFA assessments, prior therapy history (dates, doses, reasons for discontinuation or intolerance), current weight in kg, and any REMS/vaccination records.

Continuation criteria: member must be responding as evidenced by ≥ 2‑point reduction in MG‑ADL from baseline; prior authorization for continuation requires documentation of ongoing benefit and current weight.

Approval durations: initial and continuation approvals as specified in policy (e.g., up to 6 months for continuation).

Step therapy: this policy does not define an explicit step‑therapy sequence beyond the therapeutic trial requirements noted above; state or contract level requirements may impose additional sequencing.

Documentation Required

REMS / Meningococcal Infection Risk

Highlights the documentation and patient safety obligations related to meningococcal risk and provider responsibilities.

Zilbrysq REMS: ensure patient enrollment and adherence to REMS requirements prior to initiation.
Meningococcal vaccination: document vaccination at least 2 weeks prior to first dose when feasible; if vaccination cannot be completed prior to dosing, inform patient of increased risk and ensure close monitoring.
Contraindication: unresolved Neisseria meningitidis infection is a contraindication to therapy.

Documentation Required

Provider Responsibility & Required Documentation

Providers are responsible for submitting complete clinical records to support medical necessity determinations. Coverage is subject to contract terms, exclusions, and state Medicaid precedence where applicable.

Submit office chart notes, MG‑ADL and MGFA scores, anti‑AChR antibody test results, prior therapy trials (including doses, dates, and reason for failure/intolerance), current weight in kg, and REMS/vaccination documentation.
Documentation should demonstrate that the member meets all initial or continuation criteria as applicable.
When state Medicaid provisions conflict with this policy, the state Medicaid provisions take precedence.

Prior Authorization

Therapeutic Trial Requirements

Therapeutic trial requirements must be met unless contraindicated or intolerant; these are required elements of the prior authorization review.

Failure of a cholinesterase inhibitor (e.g., pyridostigmine) unless contraindicated or causes clinically significant adverse effects.
Failure of a corticosteroid (see Appendix B for examples and dosing) unless contraindicated or causes clinically significant adverse effects.
Failure of at least one immunosuppressive therapy (see Appendix B for examples such as azathioprine, mycophenolate mofetil, cyclosporine, rituximab) unless contraindicated or causes clinically significant adverse effects.
If contraindications to one or more classes exist, document the clinical rationale in the submitted records.

Note

Non‑FDA Indications

Non‑FDA indications are not authorized under this policy unless supported by the applicable off‑label use policies or evidence of coverage allowances.

Requests for indications not addressed in this policy must be supported by evidence per off‑label use policies CPCPA.09 (commercial), HIM.PA.154 (marketplace), or CP PMN.53 (Medicaid) as applicable.

Population in policyPolicy applies to adults with anti‑AChR antibody–positive gMG

Concurrent therapy contraindications

Concurrent therapy contraindications (updated 1Q 2025)Zilbrysq should not be prescribed concurrently with Bkemv, Epysqli, or Rystiggo (added during 1Q 2025 review)

Other therapies listedAlso not to be used concurrently with Soliris, Ultomiris, or Vyvgart as specified in initial criteria

Policy noteConcurrent-prescribing contraindication expansion documented in 1Q 2025 annual review