ModifiedColorado Rocky Mountain Health PlansPolicy 2025 P 2323-3

Zilbrysq® (zilucoplan) - Prior Authorization/Medical Necessity - UnitedHealthcare Commercial Plansopen_in_new

Defines prior authorization and medical necessity criteria for Zilbrysq (zilucoplan) for treatment of generalized myasthenia gravis (gMG) in adults who are anti-AChR antibody positive, including initial and reauthorization criteria, required documentation, prescribing clinician, and authorization duration.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyZilbrysq® (zilucoplan) - Prior Authorization/Medical Necessity - UnitedHealthcare Commercial Plansopen_in_new

Policy CodePolicy 2025 P 2323-3

Change TypeMODIFIED

Effective DateDec 1, 2025

Next Review Date

Key ActionSubmit medical records confirming diagnosis, anti-AChR positivity, MGFA class II-IV, MG-ADL ≥6, prior therapy history and FcRn blocker failure/intolerance if applicable, and documentation that Zilbrysq is not used with other complement inhibitors or FcRn blockers.

SourceLink

POLICY UPDATE CHANGES

Addition of criteria requiring a trial and failure, intolerance, or contraindication to an FcRn blocker.

Updated listing of examples of complement inhibitors and neonatal Fc receptor blockers without change to clinical intent.

Annual review updates reflected (P&T dates 1/2024, 1/2025, 9/2025).

12 monthsAuthorization duration

MG-ADL ≥ 6Initiation MG-ADL threshold

≥ 2 points

Reauth MG-ADL improvement required

Trial requiredFcRn blocker requirement

Coverage Summary

Defines prior authorization and medical necessity criteria for Zilbrysq (zilucoplan) for treatment of generalized myasthenia gravis (gMG) in adults who are anti-AChR antibody positive. Approval requires submission of medical records confirming diagnosis, positive anti-AChR serology, MGFA class II–IV, and baseline MG-ADL score of MG-ADL ≥ 6.

Initial criteria also require prior therapy failure: either failure of at least two immunosuppressive agents over ≥ 12 months, or failure of one immunosuppressive agent plus ≥ 4 courses of plasmapheresis/PLEX and/or IVIG over ≥ 12 months. A trial and failure (or documented intolerance/contraindication) of an FcRn blocker is required when applicable.

Zilbrysq must not be used in combination with another complement inhibitor or an FcRn blocker, must be prescribed by or in consultation with a neurologist, and authorizations (initial and reauthorization) are issued for 12 months. Reauthorization requires documentation of treatment response including at least a 2-point improvement in MG-ADL from baseline, reduction in signs/symptoms, and maintenance/reduction/discontinuation of baseline IST.

Authorization duration12 months

Initiation MG-ADL thresholdMG-ADL ≥ 6

Reauthorization MG-ADL improvement≥ 2-point reduction from pre-treatment baseline

FcRn blocker requirementTrial and failure of one FcRn blocker OR intolerance/contraindication to all FcRn blockers

Prior immunosuppressive therapy durationFailure of ≥2 immunosuppressive agents over ≥12 months OR failure of ≥1 agent plus ≥4 courses of PLEX/IVIG over ≥12 months

Initial Therapy Criteria (Prior Authorization)

Initial Authorization

Zilbrysq will be approved based on all of the following criteria:

ALL of the following

Diagnosis and baseline requirements
- Submission of medical records (e.g., chart notes, laboratory values, etc.) confirming diagnosis and baseline metrics
- Diagnosis of generalized myasthenia gravis (gMG)
- Positive serologic test for anti-AChR antibodies
- Myasthenia Gravis Foundation of America (MGFA) Clinical Classification of class II, III, or IV at initiation of therapy

Continuation (Reauthorization) Criteria

Reauthorization (Continuation) Criteria

Zilbrysq will be approved for reauthorization based on all of the following criteria:

ALL of the following

Submission of medical records (e.g., chart notes, laboratory tests) demonstrating treatment response and medication management
Clinical response requirements
- Improvement and/or maintenance of at least a 2-point improvement (reduction in score) in the MG-ADL score from pre-treatment baselineMG-ADL improvement ≥ 2 points from baseline
- Reduction in signs and symptoms of myasthenia gravis

Exclusions / Combination Therapy

Policy excludes using Zilbrysq in combination with another complement inhibitor (examples: Soliris (eculizumab), Ultomiris (ravulizumab-cwvz)) or with an FcRn blocker (examples: Imaavy (nipocalimab), Vyvgart (efgartigimod alfa), Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase), Rystiggo (rozanolixizumab) where listed).

Provider actions note that claims may be denied if Zilbrysq is used in combination with another complement inhibitor or an FcRn blocker.

Denial Risk

Combination therapy exclusion

Claims may be denied if Zilbrysq is used in combination with another complement inhibitor or an FcRn blocker (examples include Soliris (eculizumab), Ultomiris (ravulizumab-cwvz), Imaavy (nipocalimab), Vyvgart (efgartigimod alfa), Vyvgart Hytrulo).

Provider Actions & Authorization Details

Prior Authorization

Prior authorization required with documentation

Submit medical records (e.g., chart notes, laboratory values) confirming diagnosis and baseline metrics: diagnosis of generalized myasthenia gravis (gMG); positive anti-AChR antibody serology; MGFA Clinical Classification II–IV at initiation; MG-ADL total score ≥ 6 at initiation. Provide prior therapy history per policy: either failure of at least two immunosuppressive agents over ≥ 12 months, or failure of one immunosuppressive therapy plus ≥ 4 courses of plasmapheresis/PLEX and/or IVIG over ≥ 12 months. If applicable, documentation of trial and failure of an FcRn blocker or intolerance/contraindication to FcRn blockers. Also include documentation that Zilbrysq is not being used in combination with another complement inhibitor or an FcRn blocker. Prescriber is a neurologist or consult with one.

Chart notes documenting diagnosis and clinical assessments
Laboratory results including positive anti-AChR antibody test
MG-ADL scores (baseline and dates) showing ≥ 6 at initiation
MGFA classification documentation (class II–IV)
Prior therapy timeline showing immunosuppressive agent trials and PLEX/IVIG courses
Documentation of FcRn blocker trial and failure, or intolerance/contraindication

Applicable Codes

Relevant diagnosis codes (examples referenced; program may use ICD-10 claim logic)ICD-10

No codes listed

Drug/HCPCS/NDC coding (not specified in policy text)mixed

No codes listed

Clinical Evidence & Background

Zilbrysq (zilucoplan) is a complement inhibitor indicated for treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-AChR antibody positive.

The policy aligns prior authorization and medical necessity criteria to clinical trial endpoints (MG-ADL) and prior therapy requirements used in the RAISE study and prescribing information. Initial approval thresholds mirror trial entry criteria (e.g., MG-ADL ≥ 6, MGFA class II–IV) and reauthorization criteria mirror clinical response endpoints (e.g., MG-ADL improvement ≥ 2 points).

RAISEKey phase 3 trial: RAISE (Lancet Neurol. 2023)

PI Apr 2024Prescribing information: Zilbrysq package insert, April 2024

MG-ADL: The Myasthenia Gravis Activities of Daily Living scale used to quantify symptom severity; policy uses score thresholds for initiation (MG-ADL ≥ 6) and response (≥ 2-point improvement from baseline).

MGFA: The Myasthenia Gravis Foundation of America Clinical Classification; policy requires class II–IV at initiation of therapy.

FcRn blocker: Neonatal Fc receptor blockers (examples include Imaavy (nipocalimab), Rystiggo (rozanolixizumab), Vyvgart (efgartigimod alfa), and Vyvgart Hytrulo), for which the policy requires trial and failure or documented intolerance/contraindication when applicable.

Revision History

9/2025material_changeLatest

Addition of criteria requiring a trial and failure, intolerance, or contraindication to an FcRn blocker.

9/2025addedLatest

Updated list of FcRn blocker examples included.

1/2025revised

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyZilbrysq® (zilucoplan) - Prior Authorization/Medical Necessity - UnitedHealthcare Commercial Plansopen_in_new

Policy CodePolicy 2025 P 2323-3

Change TypeMODIFIED

Effective DateDec 1, 2025

Next Review Date

SourceLink

On This Page

Myasthenia Gravis Activities of Daily Living scale (MG-ADL) total score ≥ 6 at initiation of therapyMG-ADL ≥ 6

Prior therapy - one of

History of failure of at least two immunosuppressive agents over the course of at least 12 months (e.g., azathioprine, corticosteroids, cyclosporine, methotrexate, mycophenolate, etc.)failure of ≥ 2 agents over ≥ 12 months
History of failure of at least one immunosuppressive therapy and required four or more courses of plasmapheresis/plasma exchanges and/or intravenous immune globulin over the course of at least 12 months without symptom control≥ 4 courses over ≥ 12 months

FcRn blocker requirement - one of

History of failure to one FcRn blocker (e.g., Imaavy (nipocalimab), Vyvgart (efgartigimod alfa), Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase))
Intolerance or contraindication to all FcRn blockers (i.e., Imaavy (nipocalimab), Rystiggo (rozanolixizumab), Vyvgart (efgartigimod alfa), Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase))

Patient is not receiving Zilbrysq in combination with another complement inhibitor (e.g., Soliris (eculizumab), Ultomiris (ravulizumab-cwvz)) or an FcRn blocker (e.g., Imaavy, Vyvgart, Vyvgart Hytrulo)

Prescribed by, or in consultation with, a neurologist

Maintenance, reduction, or discontinuation of dose(s) of baseline immunosuppressive therapy (IST) prior to starting Zilbrysq

Add on, dose escalation of IST, or additional rescue therapy from baseline while on Zilbrysq is considered treatment failure

Patient is not receiving Zilbrysq in combination with another complement inhibitor (e.g., Soliris (eculizumab), Ultomiris (ravulizumab)) or an FcRn blocker (e.g., Imaavy (nipocalimab), Vyvgart (efgartigimod alfa), Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase))

Prescribed by, or in consultation with, a neurologist

Documentation Required

Reauthorization documentation

Submit medical records for reauthorization showing all of the following: at least a 2-point improvement (reduction) in MG-ADL from pre-treatment baseline, reduction in signs and symptoms of myasthenia gravis, and maintenance, reduction, or discontinuation of baseline immunosuppressive therapy (IST). Note: add-on therapy, dose escalation of IST, or additional rescue therapy while on Zilbrysq is considered treatment failure.

Billing Rule

Authorization duration

Authorizations, both initial and for reauthorization, will be issued for 12 months.

Documentation Required

Prescriber specialty requirement

Zilbrysq must be prescribed by, or in consultation with, a neurologist.

Updated listing of examples of complement inhibitors and neonatal Fc receptor blockers without change to clinical intent.

1/2024program_status

Program created / Prior Authorization/Medical Necessity program established.

12/1/2025status_effective_date

Effective date for the program set to 12/1/2025.