ModifiedEmblemHealthPolicy N/A

Complement Inhibitors — Eculizumab Products Utilization Management Medical Policy

Medical benefit prior-authorization and coverage criteria for eculizumab (Soliris and biosimilars) for Medicare Advantage lines of business; defines indications, dosing, and approval durations for aHUS, gMG, PNH, NMOSD, and select other uses.

Policy Summary

PayerEmblemHealth

PolicyComplement Inhibitors — Eculizumab Products Utilization Management Medical Policy

Policy CodePolicy N/A

Change TypeMaterial revisions and biosimilars added

Effective Date04/08/2025

Next Review DateN/A

Key ActionSubmit prior authorization with indication-specific diagnostic documentation and dosing consistent with listed regimens.

SourceLink

POLICY UPDATE CHANGES

Bkemv (biosimilar to Soliris) was added to the policy; the same criteria apply as that for Soliris.

Epysqli (biosimilar to Soliris) was added to the policy; the same criteria apply as that for Soliris.

Generalized Myasthenia Gravis age requirement for initial and continuation therapy was changed to ≥ 26 years of age (previously ≥ 18 years).

Removed criteria requiring evidence of clinically significant hemolysis or documented history of a major adverse event from thromboembolism from PNH indication.

Removed from aHUS indication requirement that TTP be ruled out (e.g., normal ADAMTS13) or that trial of plasma exchange failed.

Neuromyelitis Optica Spectrum Disorder criteria were separated into Initial Therapy and Patients Currently Receiving Soliris, with approval duration, age restriction, diagnosis confirmation, and specialist requirement retained.

MALine(s) of business

aHUS,gMG,PNH,NMOSDIndications

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

1y / 6mTypical approval

Bkemv,EpysqliBiosimilars

Boxed WarningSafety REMS

Recommended Authorization Criteria

Atypical Hemolytic Uremic Syndrome (aHUS) - Initial and Dosing

Approve for 1 year if the patient does not have signs of Shiga toxin E. coli–related hemolytic uremic syndrome and dosing matches weight‑based regimens.

aHUS approval: Patient does not have signs of Shiga toxin E. coli–related hemolytic uremic syndrome

IC-L

Dosing meets regimen: Dose meets specified weight‑based induction and maintenance regimens (examples include adult regimen: 900 mg IV weekly x4 then 1200 mg at week 5 then 1200 mg every 2 weeks; pediatric weight‑based regimens for 30–40 kg, 10–20 kg, 5–10 kg as listed)

dosing specifics in chunk 11

Generalized Myasthenia Gravis (gMG) - Initial and Continuation

Approve Soliris if the patient meets antibody status and treatment history criteria; initial therapy approved for 6 months when criteria met; continuation approvals typically for 1 year when patient is deriving benefit per prescriber.

Eligibility: Confirmed anti‑acetylcholine receptor (anti‑AChR) antibody–positive generalized myasthenia gravis

IC-L

Initial therapy prerequisites: Patient is ≥ 6 years of age AND has received or is receiving, or had inadequate efficacy, contraindication, or significant intolerance to at least one conventional therapy (examples include pyridostigmine, a corticosteroid, azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, tacrolimus, cyclophosphamide)

IC-ISGP

Initial approval duration: Initial therapy approval duration: 6 months

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Dosing meets regimen: Dose administered IV and meets listed adult or pediatric weight‑based induction and maintenance regimens (e.g., adult: 900 mg weekly x4 then 1200 mg at week 5 then 1200 mg q2w; pediatric regimens by weight as listed)

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Paroxysmal Nocturnal Hemoglobinuria (PNH) - Initial and Continuation

Approve if adult diagnosis is confirmed by peripheral blood flow cytometry or if patient is currently receiving eculizumab and deriving benefit; initial approvals noted for 6 months and continuation approvals typically for 1 year when benefit continues.

Eligibility: Patient ≥ 18 years AND diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) confirmed by peripheral blood flow cytometry showing absence or deficiency of GPI‑anchored proteins on at least two cell lineages

IC-COMP / IC-ISGP

Continuation: Patient currently receiving eculizumab and continuing to derive benefit according to the prescriber for continuation approval

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Dosing: Dose meets listed induction and maintenance regimens (examples include 600 mg IV weekly x4 induction or 900 mg IV weekly x4 then 1200 mg thereafter per weight‑based guidance)

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Neuromyelitis Optica Spectrum Disorder (NMOSD) - Initial and Continuation

Approve for adults ≥ 18 years with positive anti‑aquaporin‑4 (AQP4) antibody for initial therapy (1 year) or for patients currently receiving eculizumab and deriving clinical benefit.

Eligibility: Patient ≥ 18 years AND diagnosis confirmed by a positive blood serum test for anti‑aquaporin‑4 (AQP4) antibody

IC-L

Initial approval: Initial therapy approval duration: 1 year

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Continuation: Patient currently receiving eculizumab and deriving clinical benefit per prescriber for continuation approval

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Dosing: Dose administered IV and meets listed induction and maintenance regimens (e.g., 900 mg weekly x4 induction OR 1200 mg every 2 weeks maintenance as specified)

Dense Deposit Disease (Other use with supportive evidence)

Approve for 1 year if biopsy‑proven dense deposit disease and documented elevated serum sC5b‑9 (SMAC).

Eligibility: Biopsy‑proven dense deposit disease AND documented elevated serum sC5b‑9 (serum membrane attack complex) levels

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Dosing: Induction 900 mg IV weekly x4; maintenance 1200 mg IV every 14 days starting at week 5

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Summary of criteria changes and current structural notes

Summary of revisions affecting indication‑specific criteria, age thresholds, biosimilar additions, and continuation rules.

biosimilars: Bkemv and Epysqli were added to the policy with the same criteria as Soliris.

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gMG age requirement: Age requirement for generalized myasthenia gravis changed to ≥ 26 years for initial and continuation therapy.>=26 years

Corticosteroid added to examples of immunosuppressant therapies.

PNH criteria removed: Removed requirement for evidence of clinically significant hemolysis or documented history of a major thromboembolic event for PNH indication.

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Eculizumab is not indicated for the treatment of patients with Shiga toxin–producing Escherichia coli–related hemolytic uremic syndrome.

Companion Medicare coverage documents and articles may list specific HCPCS or ICD‑10 codes for reference, but the presence or absence of a given code alone is not sufficient to approve coverage; coding should be considered alongside documented clinical criteria and supporting evidence.

Coverage is not recommended for circumstances that are not expressly listed in the Recommended Authorization Criteria. The criteria will be updated as new published data become available; requests outside the stated criteria should be expected to be denied unless supporting evidence justifies exception.

Criteria for Initiating Therapy

Initial therapy criteria — indication-specific time limits and diagnostic/dosing requirements

Initial therapy approvals have indication‑specific time limits and require documented diagnostic confirmation and dosing consistent with the listed regimens.

aHUS initial: Approve for 1 year if patient is not Shiga toxin–related HUS and dosing meets weight‑based induction/maintenance regimens

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gMG initial: Approve for 6 months if patient meets: confirmed anti‑AChR antibody positivity, age requirement (see policy), and prior use/intolerance/inadequate response to at least one conventional therapy

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PNH initial: Approve initial therapy (duration noted in policy) if PNH diagnosis is confirmed by peripheral blood flow cytometry

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Criteria for Continuing Therapy

Continuation therapy rules — ongoing clinical benefit required; prescriber documentation needed

Continuation approvals are allowed when the prescriber documents that the patient is continuing to derive clinical benefit; continuation durations are typically 1 year.

gMG continuation: Patient is continuing to derive benefit from eculizumab according to the prescriber for continuation approval (approve for 1 year)

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PNH continuation: Patient currently receiving eculizumab and deriving benefit per prescriber for continuation approval (approve for 1 year)

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NMOSD continuation: Patient currently receiving eculizumab and deriving clinical benefit per prescriber for continuation approval (approve for 1 year)

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What Providers Must Do

Prior Authorization

Prior Authorization Required

Prior authorization is required for medical benefit coverage of eculizumab and its biosimilars when the applicable coverage criteria are met. Approval will be granted only when documentation supports the requested indication and dosing.

Prior authorization required for eculizumab products (including Soliris, Bkemv, Epysqli) — same criteria apply to biosimilars

Documentation Required

Approval Durations and Dosing Requirements

Approvals are time-limited and vary by indication. Ensure the request specifies the intended indication and matches the approval duration below; dosing must conform to the indication-specific dosing rules in the Criteria and Dosing sections.

Atypical Hemolytic Uremic Syndrome (aHUS): initial approval = 1 year; dosing per aHUS weight-based schedule
Generalized Myasthenia Gravis (gMG): initial therapy = 6 months; continuation approvals = 1 year if clinical benefit is documented; dosing per gMG IV schedule

Step Therapy Requirements and Exceptions

Requirement	Details
Required prior use or intolerance of conventional therapies
Patient received or is currently receiving, or had inadequate efficacy, contraindication, or significant intolerance to at least one conventional therapy (examples include pyridostigmine, a corticosteroid, azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, tacrolimus, cyclophosphamide)

Exception	Policy note
NMOSD step therapy exception
Note created to allow an exception to previously tried systemic therapies for patients who have tried Enspryng (satralizumab) or Uplizna (inebilizumab)

Medicare Coverage Documents and Coding References

Referenced Medicare Coverage Documentsmixed

LCD L33394 / Article A54548

Medicare Local Coverage Determination and Local Coverage Article referenced for eculizumab

Soliris and Biosimilar Products

Note

Soliris and biosimilars managed under same UM framework

Eculizumab (Soliris) and its biosimilars are managed under the same utilization framework; policy language and criteria apply across these products.

Note

Bkemv added — same criteria as Soliris

Bkemv (biosimilar to Soliris) was added to the policy; the same indication-specific criteria and utilization management rules that apply to Soliris apply to Bkemv.

Note

Epmysqli added — same criteria as Soliris

Epysqli (biosimilar to Soliris) was added to the policy; the same indication-specific criteria and utilization management rules that apply to Soliris apply to Epysqli.

Key Definitions and Reference Terms

Atypical Hemolytic Uremic Syndrome (aHUS) — definition

DefinitionA subtype of hemolytic uremic syndrome (HUS) in which thrombotic microangiopathy results from dysregulation of the complement system leading to endothelial damage in renal and other microvasculature; distinct from typical (Shiga toxin–related) HUS.

Key clinical triadNon‑immune hemolytic anemia, thrombocytopenia, and acute renal failure due to systemic thrombotic microangiopathy.

Distinguishing noteEculizumab is not indicated for Shiga toxin–producing Escherichia coli–related (typical) HUS.

Relevance to policyPolicy approval for aHUS requires absence of signs of Shiga toxin E. coli–related HUS and adherence to specified weight‑based induction and maintenance dosing regimens (initial approval typically 1 year).

Paroxysmal Nocturnal Hemoglobinuria (PNH) — definition

Policy Summary

PayerEmblemHealth

PolicyComplement Inhibitors — Eculizumab Products Utilization Management Medical Policy

Policy CodePolicy N/A

Change TypeMaterial revisions and biosimilars added

Effective Date04/08/2025

Next Review DateN/A

Key ActionSubmit prior authorization with indication-specific diagnostic documentation and dosing consistent with listed regimens.

SourceLink

On This Page

Continuation: Patient is continuing to derive benefit from eculizumab per prescriber for continuation approval (approve for 1 year)

aHUS criteria removed:

Removed requirement that TTP be ruled out (for example, normal ADAMTS13) or that a trial of plasma exchange failed from the aHUS indication; continuation criteria removed from this indication.

NMOSD initial therapy change: Removed criterion requiring use of two systemic therapies for NMOSD initial therapy; NMOSD criteria separated into Initial Therapy and Patients Currently Receiving Soliris with approval duration, age restriction, diagnosis confirmation, and specialist requirement retained. Exception note added for patients who previously tried Enspryng or Uplizna.

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NMOSD initial: Approve for 1 year if patient ≥ 18 years and diagnosis confirmed by positive anti‑AQP4 antibody test

Initial therapy changes — NMOSD and other revisions including removed requirement for two systemic therapies and exceptions

Key recent revisions to initial therapy criteria, including NMOSD and other updates.

NMOSD step therapy removed: Removed requirement that patients trial two systemic therapies before NMOSD initial therapy; Soliris is listed as a first‑line option per NEMOS 2024 recommendations.

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NMOSD exceptions: Exception allowed for patients who have previously tried Enspryng or Uplizna (note created to allow exception to prior systemic therapy requirement).

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gMG examples updated: Examples of conventional therapies for gMG were updated to explicitly include corticosteroid among immunosuppressant examples.

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Continuation therapy notes — revisions and removals across indications (aHUS, others)

Notes on recent revisions to continuation criteria across indications.

Removed aHUS continuation: Continuation criteria were removed for aHUS in the referenced policy update.

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Updated wording for continuing benefit: For gMG and PNH patients currently receiving Soliris, examples of continuing benefit were changed to Notes and prescriber wording was updated to 'prescriber'.

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Continuation criteria revisions summary: Continuation criteria were revised in multiple indications; example measures of benefit (eg, FACIT‑Fatigue score) were added to notes where applicable.

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Paroxysmal Nocturnal Hemoglobinuria (PNH): initial approvals and continuation approvals = 1 year; confirm diagnosis by peripheral blood flow cytometry; dosing per PNH IV schedule

Neuromyelitis Optica Spectrum Disorder (NMOSD): initial and continuation approvals = 1 year; dosing per NMOSD IV schedule

Prior Authorization

gMG Prior Treatment Requirement

For generalized myasthenia gravis (gMG) initial therapy, the patient must have anti-acetylcholine receptor antibody–positive gMG and be at least the age required by the policy for initial therapy. Initial therapy requires prior use, current use, or inadequate response to at least one conventional therapy (examples include pyridostigmine, a corticosteroid, azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, tacrolimus, cyclophosphamide) unless contraindicated or not tolerated.

Initial therapy: documentation of prior use/current use or inadequate response to ≥1 conventional therapy, or documented contraindication/intolerance
Age requirement per policy for initial therapy (see Criteria)

Documentation Required

NMOSD Diagnostic Documentation

For Neuromyelitis Optica Spectrum Disorder (NMOSD), a positive blood serum test for anti–aquaporin-4 (AQP4) antibody is required to support initial therapy. For patients currently receiving eculizumab, documentation of a positive anti‑AQP4 antibody test and prescriber‑documented clinical benefit are required for continuation.

Initial therapy: positive anti‑AQP4 antibody test required
Continuation: positive anti‑AQP4 antibody test and prescriber statement of clinical benefit

Documentation Required

PNH Diagnostic Documentation

Documentation of Paroxysmal Nocturnal Hemoglobinuria (PNH) must include confirmation by peripheral blood flow cytometry demonstrating absence or deficiency of GPI‑anchored proteins on at least two cell lineages.

Include peripheral blood flow cytometry report showing GPI‑anchored protein deficiency/absence on ≥2 cell lineages

Billing Rule

Coding Is Not Determinative

The presence or absence of HCPCS, CPT, or ICD‑10 codes alone does not determine coverage. Code lists cited from Medicare NCDs/LCDs or companion articles are for reference only and do not by themselves authorize approval or denial.

Do not rely solely on HCPCS or ICD‑10 codes to support medical necessity requests
Include clinical documentation and test results that satisfy the criteria in this policy

Note

References and Coding Guidance

This policy incorporates Medicare National and Local Coverage Determinations and companion articles; these sources (including referenced HCPCS and ICD‑10 lists) are cited in the Sources of Information/References. Use those code lists for billing guidance only — clinical documentation must meet policy criteria for coverage.

Consult the Sources of Information/References section for Medicare guidance and companion article code lists
Referenced code lists are informational and not sufficient alone to approve coverage

A rare, genetic disorder of hematopoietic stem cells caused by a PIGA gene mutation resulting in deficiency of GPI‑anchored proteins on blood cells, leading to complement‑mediated intravascular hemolysis, thrombosis, and cytopenias.

Diagnostic confirmationDiagnosis should be confirmed by peripheral blood flow cytometry demonstrating absence or severe deficiency of GPI‑anchored proteins on at least two cell lineages.

Clinical consequencesComplications include hemolytic anemia, thrombosis, and peripheral blood cytopenias; prior to complement inhibitors, management was primarily supportive.

Clinical and guideline sources cited

Prescribing informationSoliris (eculizumab) intravenous infusion prescribing information (Alexion); June 2024.

Consensus guidance for aHUSCampistol JM et al., An update for atypical haemolytic uraemic syndrome: diagnosis and treatment: consensus document (Nefrologia 2015).

PNH and general reviewsCancado RD et al., Consensus statement for diagnosis and treatment of PNH (Hematol Transfus Cell Ther. 2021); Shah N, Bhatt H., Paroxysmal Nocturnal Hemoglobinuria (StatPearls, updated 2023).

NMOSD and gMG guidanceWingerchuk DM et al., International consensus diagnostic criteria for NMOSD; International consensus guidance for management of myasthenia gravis (Neurology 2016); NEMOS 2024 recommendations cited.

Medicare coverage documentsLCD L33394 and Local Coverage Article A54548 (CMS National Government Services) referenced for coverage and coding guidance.

Eculizumab is a monoclonal complement C5 inhibitor indicated for several rare, complement‑mediated disorders including atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), generalized myasthenia gravis (AChR antibody–positive), and neuromyelitis optica spectrum disorder (AQP4 antibody–positive). It carries a boxed warning for serious meningococcal infections and is available only through a restricted access program (REMS).