ModifiedCentenePolicy CP PHAR.97

Eculizumab (Soliris) and biosimilars coverage

Defines medical necessity, prior authorization, and dosing criteria for Soliris and its biosimilars (eculizumab-aeeb, eculizumab-aagh) across indications including PNH, aHUS, gMG, and NMOSD for Centene lines of business.

Policy Summary

PayerCentene

PolicyEculizumab (Soliris) and biosimilars coverage

Policy CodePolicy CP PHAR.97

Change TypeMaterial updates and clarifications (biosimilars, non-concurrency, approval duration)

Effective Date03.01.12

Next Review Date

Key ActionSubmit prior authorization with documentation that the member meets all indication-specific approval criteria and specialty consultation as required.

SourceLink

POLICY UPDATE CHANGES

Added newly approved biosimilar Bkemv and updated Soliris concurrent-therapy restrictions to include additional therapies for gMG and PNH.

Added biosimilar Epysqli and updated its FDA-approved indication to include adult patients with gMG who are AChR antibody positive.

Revised continued approval duration from 6 to 12 months for all indications classified as chronic conditions.

Added PiaSky to the list of therapies that should not be prescribed concurrently with Soliris/Bkemv/Epijkstra for PNH.

For gMG, clarified that the required immunosuppressive therapy should be non-steroidal.

4FDA-approved indications listed

12 monthsContinued therapy approval duration

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3biosimilars/agents referenced

6 moInitial approval duration

Coverage Criteria for Eculizumab (Soliris) and Biosimilars

Initial Therapy: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Covered when ALL of the following are met

PNH Initial: 1) Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH); 2) Prescribed by or in consultation with a hematologist; 3) Flow cytometry shows detectable GPI-deficient hematopoietic clones or 10% PNH cells; 4) Age 18 years; 5) Member meets one of the following: (a) History of 1 red blood cell transfusion in the past 24 months AND (i) hemoglobin < 7 g/dL in members without anemia symptoms OR (ii) hemoglobin < 9 g/dL in members with anemia symptoms; OR (b) History of thrombosis; 6) Provider attestation of presence or absence of concomitant Empaveli (pegcetacoplan) therapy; 7) Dosing does not exceed 600 mg per week for the first 4 weeks followed by 900 mg for the fifth dose 1 week later, then 900 mg every 2 weeks thereafter.age >=18

Approval duration: 6 months

Initial Therapy: Atypical Hemolytic Uremic Syndrome (aHUS)

Covered when ALL of the following are met

aHUS Initial: 1) Diagnosis of atypical hemolytic uremic syndrome (aHUS; complement-mediated HUS); 2) Prescribed by or in consultation with a hematologist or nephrologist; 3) Age 2 months; 4) Platelet count < 150 x 10^9/L; 5) Member has signs of thrombotic microangiopathy (TMA) evidenced by hemolysis (e.g., elevated LDH), thrombocytopenia, and renal involvement (e.g., serum creatinine above upper limit of normal or requirement for dialysis); 6) Documentation that member does NOT have ADAMTS13 deficiency or STEC-HUS; 7) Soliris/Bkemv/Epysqli is not prescribed concurrently with Ultomiris; 8) Dosing: for age 18 years: 900 mg weekly x4 then 1200 mg for fifth dose 1 week later then 1200 mg every 2 weeks; for age 2 months to <18 years: FDA‑approved weight‑based pediatric dosing; additional doses may be approved in setting of concomitant plasmapheresis/plasma exchange/fresh frozen plasma infusion (see Appendix E).

Initial Therapy: Generalized Myasthenia Gravis (gMG)

Covered when ALL of the following are met

gMG Initial: 1) Diagnosis of generalized myasthenia gravis (gMG); 2) Prescribed by or in consultation with a neurologist; 3) Age 6 years; 4) MGFA clinical classification Class II to IV; 5) MG-ADL score 6 at baseline; 6) Positive anti‑AChR antibody; 7) Failure of a corticosteroid unless contraindicated; 8) Failure of a cholinesterase inhibitor unless contraindicated; 9) Failure of at least one non‑steroidal immunosuppressive therapy unless contraindicated; 10) Soliris/Bkemv/Epysqli is not prescribed concurrently with Rystiggo, Ultomiris, Vyvgart, Vyvgart Hytrulo, or Zilbrysq; 11) Dosing per FDA‑approved regimen (age‑based); additional doses may be approved with concomitant plasmapheresis/plasma exchange/fresh frozen plasma infusion or IVIg (see Appendix E).

Initial Therapy: Neuromyelitis Optica Spectrum Disorder (NMOSD)

Covered when ALL of the following are met

NMOSD Initial: 1) Diagnosis of neuromyelitis optica spectrum disorder (NMOSD); 2) Prescribed by or in consultation with a neurologist; 3) Age 18 years; 4) Positive anti‑AQP4 antibody; 5) Member meets one of the following relapse criteria: history of 2 relapses in prior 12 months OR 3 relapses in prior 24 months with at least one in last 12 months; 6) Baseline EDSS score < 7; 7) Failure of rituximab at maximally indicated doses unless contraindicated; 8) Soliris/Bkemv/Epysqli is not prescribed concurrently with rituximab, Enspryng, or Ultomiris; 9) Dosing does not exceed 900 mg weekly x4 then 1200 mg for fifth dose 1 week later then 1200 mg every 2 weeks thereafter.

Continued Therapy Criteria (by indication)

Covered when ALL of the following are met for continuation

Continued Therapy General: 1) Member is currently receiving medication via Centene benefit or has previously met initial approval criteria; 2) Member is responding positively to therapy as evidenced by indication‑specific improvements: PNH — normalization of LDH, reduced transfusion need, stabilization/increase in hemoglobin, reduced fatigue, fewer thrombotic events, improved quality of life; aHUS — improved hemolysis (e.g., LDH), increased/stabilized platelet counts, improved/stabilized serum creatinine or eGFR, reduced need for dialysis; gMG — 2‑point reduction from baseline in MG‑ADL total score; NMOSD — improvement or stabilization in relapse frequency, EDSS, or visual acuity; 3) Drug is not prescribed concurrently with disallowed agents per indication (e.g., PNH: Empaveli, Fabhalta, PiaSky, Ultomiris; aHUS: Ultomiris; gMG/NMOSD: see indication sections); 4) If request is for a dose increase, new dose does not exceed indication‑specific maximums (PNH: 900 mg q2w; aHUS: 1200 mg q2w; gMG/NMOSD: 1200 mg q2w); Approval duration: 12 months.

Dosage and supplemental dosing criteria

Dosing and supplemental dosing conditions

Standard adult dosing for PNH/gMG/NMOSD/aHUS: Adults: induction and maintenance dosing per FDA‑approved regimens: PNH — IV infusion 600 mg weekly for first 4 weeks, then 900 mg for fifth dose 1 week later, then 900 mg every 2 weeks (maximum 900 mg/dose); aHUS adults — 900 mg weekly x4 then 1,200 mg for fifth dose then 1,200 mg q2w (maximum 1,200 mg/dose); gMG and NMOSD adults — induction 900 mg weekly x4 then 1,200 mg for fifth dose then 1,200 mg q2w (maximum 1,200 mg/dose).

See Sections V and Appendix E for pediatric and weight‑based dosing and for exceptions.

Supplemental dosing with interventions: Supplemental eculizumab doses are required with plasmapheresis/plasma exchange or fresh frozen plasma infusion and in some IVIg scenarios: examples — if most recent eculizumab dose = 300 mg, supplemental 300 mg per plasmapheresis session; if most recent dose = 600 mg, supplemental 600 mg per session; fresh frozen plasma infusion — supplemental 300 mg per infusion; IVIg: supplemental dosing depends on frequency and most recent eculizumab dose (see Appendix E and chunk 28 for specific tables).

Supplemental dosing may be approved only when documentation of the intervention is provided.

General coverage conditions

Covered when ALL applicable FDA/label and policy-specific requirements are met (per-indication criteria referenced elsewhere in the full policy).

General coverage conditions: Approval requires meeting FDA‑approved indication(s) and adherence to policy‑specific requirements including non‑concurrency with specified therapies, appropriate specialist prescribing or consultation, required diagnostic and response documentation, and adherence to dosing limits; continuation approvals for chronic indications are granted for 12 months.

Supplemental dosing may be approved if member is receiving plasmapheresis, plasma exchange, fresh frozen plasma, or IVIg; prior authorization and HCPCS coding apply (see policy).

Coverage is not authorized for STEC-HUS and for non‑FDA approved indications that are not addressed in this policy unless the request includes sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage documents.

Requests for the following diagnoses are specifically excluded from coverage: STEC‑HUS, antiphospholipid syndrome (D68.61), and unspecified nephritic syndrome with other morphologic changes (N0S.8). Use of eculizumab, Bkemv, or Epysqli for these and other non‑FDA indicated conditions is considered investigational or not authorized unless supported by the off‑label use policies or other formal evidence of coverage.

Concurrent prescribing of Soliris, Bkemv, or Epysqli with certain other complement‑ or immune‑modulating therapies is restricted and may result in denial if used outside permitted exceptions. Examples of therapies listed in the policy as not to be prescribed concurrently include Empaveli, Ultomiris, Rystiggo, Vyvgart, Vyvgart Hytrulo, Zilbrysq, Fabhalta, and most recently PiaSky. For aHUS, the policy explicitly states that Soliris/Bkemv/Epquelize (Epysqli) must not be prescribed concurrently with Ultomiris.

Use of Soliris, Bkemv, or Epysqli for indications that are not FDA‑approved and are not addressed by this policy is considered not authorized unless the provider supplies sufficient documentation demonstrating efficacy and safety consistent with the applicable off‑label use policies. Such requests should reference the off‑label policy pathway and provide the clinical evidence required by those policies.

Use of Soliris, Bkemv, or Epysqli for listed excluded indications is considered investigational due to lack of conclusive randomized controlled trial evidence. The policy provides example alternative therapies for some excluded diagnoses (e.g., immunosuppression for unspecified nephritic syndrome) and indicates that investigational uses are not authorized absent robust evidence.

Coding or billing requests that do not align with the policy’s specified indications and coding guidance may not guarantee coverage. The policy’s HCPCS entries (for example, J1299, Q5151, Q5152) are provided for informational purposes only; inclusion of a code does not ensure payment and providers must follow current professional coding guidance when submitting claims.

Coding and Billing Guidance

Diagnoses Not AuthorizedICD-10Not Covered

D68.61	Antiphospholipid syndrome
N0S.8	Unspecified nephritic syndrome with other morphologic changes

Diagnoses excluded from coverageICD-10Not Covered

D68.61	Antiphospholipid syndrome
N0S.8	Unspecified nephritic syndrome with other morphologic changes

HCPCS / billing codes referencedHCPCS

J1299	Injection, eculizumab, 2 mg
Q5151	Injection, eculizumab-aagh (epysqli) biosimilar, 2 mg
Q5152	Injection, eculizumab-aeeb (bkemv) biosimilar, 2 mg
Q5139	HCPCS code previously added/removed per updates
J1300	HCPCS code removed per updates
J3590	HCPCS code removed per updates
C9399	HCPCS code removed per updates

Clinical thresholds and response measures (examples)

MG-ADL baseline for gMG initiationMG-ADL score ≥6 at baseline is required for initiation of therapy for generalized myasthenia gravis.

MG-ADL for continuationContinued approval requires a clinical response such as a ≥2-point reduction in MG-ADL from baseline.

Hemoglobin transfusion thresholds for PNHHistory of ≥1 RBC transfusion in past 24 months with hemoglobin <7 g/dL in members without anemia symptoms or <9 g/dL in members with anemia symptoms.

Platelet count requirement for aHUSPlatelet count <150 x10^9/L and evidence of thrombotic microangiopathy (hemolysis/LDH elevation and renal involvement) are required for aHUS initial approval.

LDH as hemolysis marker for PNH continuationNormalization or reduction in LDH consistent with decreased hemolysis is used as evidence of response for continued therapy in PNH.

Provider Actions, Authorization and Documentation Requirements

Documentation Required

Provider action: Documentation required

Prior Authorization Required — Prior authorization requires documentation that the member meets all indication-specific initial approval criteria and that the drug is prescribed by or in consultation with the appropriate specialist (e.g., hematologist, nephrologist, neurologist). Provider must submit documentation (such as office chart notes, lab results, vaccination records, medication history, and other clinical information) supporting that the member has met all approval criteria. Failure to submit required documentation may result in denial or delay of the request.

Documentation should include relevant specialist consultation notes when required (hematology for PNH, nephrology for aHUS, neurology for gMG and NMOSD).
Include vaccination documentation for meningococcal vaccine administered ≥2 weeks prior to first dose when possible, or documentation of an appropriate risk discussion and plan if urgent therapy is needed.
For initial and continuation requests include medication history showing prior therapies tried and response, transfusion history (for PNH), and any prior dosing/administration records.

Documentation Required

Provider action: Diagnostic test expectations

Background and Clinical Context

Eculizumab and its biosimilars (eculizumab‑aeeb/Bkemv and eculizumab‑aagh/Epysqli) are terminal complement C5 inhibitors used to reduce complement‑mediated hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), to treat complement‑mediated thrombotic microangiopathy in atypical hemolytic uremic syndrome (aHUS), and to manage certain antibody‑mediated neurologic conditions such as AChR‑positive generalized myasthenia gravis (gMG) and AQP4‑antibody positive neuromyelitis optica spectrum disorder (NMOSD). The policy references specific diagnostic and response biomarkers (for example, flow cytometry for GPI‑deficient clones in PNH, platelet count and LDH for aHUS, MG‑ADL for gMG, and AQP4 seropositivity and EDSS for NMOSD) to support initiation and continuation decisions.

Definitions and Abbreviations

PNH — definition and references

Definition: PNHPNH: paroxysmal nocturnal hemoglobinuria.

Reference literaturePNH diagnostic and management literature is referenced (e.g., Parker et al., Blood 2005).

Abbreviation contextPNH is listed in the policy abbreviation appendix as paroxysmal nocturnal hemoglobinuria.

aHUS — definition and references

Definition: aHUSaHUS: atypical hemolytic uremic syndrome.

Consensus guidance referencedInternational consensus guidance for aHUS management is referenced (Loirat et al.; Pediatr Nephrol. 2016) and other adult recommendations noted.

Revision History and Material Changes

2024-07-25added

RT4 3Q 2024 annual review: added biosimilars Bkemv and Epysqli, updated concurrent-therapy restrictions to include Rystiggo, Vyvgart Hytrulo, Zilbrysq (gMG), Fabhalta (PNH), and Ultomiris (NMOSD); updated Epysqli FDA indication to include adult gMG AChR-positive patients; HCPCS code changes applied.

2025-06-24revisedLatest

3Q 2025 annual review: updated Bkemv FDA indication to include adult gMG AChR-positive patients; added PiaSky to PNH non-concurrency list; clarified that required immunosuppressive therapy for gMG should be non-steroidal; revised continued approval duration from 6 to 12 months for chronic indications.

Policy Summary

PayerCentene

PolicyEculizumab (Soliris) and biosimilars coverage

Policy CodePolicy CP PHAR.97

Change TypeMaterial updates and clarifications (biosimilars, non-concurrency, approval duration)

Effective Date03.01.12

Next Review Date

Key ActionSubmit prior authorization with documentation that the member meets all indication-specific approval criteria and specialty consultation as required.

SourceLink

On This Page

Supplemental eculizumab dosing with plasmapheresis/IVIg (Appendix E)

Supplemental dosing with plasmapheresis/plasma exchange (most recent dose = 300 mg)Supplemental eculizumab dose with each plasmapheresis or plasma exchange session = 300 mg when most recent eculizumab dose = 300 mg.

Supplemental dosing with plasmapheresis/plasma exchange (most recent dose = 600 mg)Supplemental eculizumab dose with each plasmapheresis or plasma exchange session = 600 mg when most recent eculizumab dose = 600 mg.

Fresh frozen plasma infusion supplementSupplemental eculizumab dose with each infusion of fresh frozen plasma = 300 mg regardless of most recent dose (example listing includes most recent dose = 2300 mg).

IVIg acute rescue therapyNo supplemental eculizumab dose needed for IVIg given as acute rescue therapy per Appendix E.

IVIg frequent dosing interactionWhen IVIg is administered with frequency ≥ every 4 weeks, supplemental dosing may be 600 mg (or 300 mg) at same time as scheduled eculizumab dose depending on most recent eculizumab dose as specified in Appendix E.

Continued approval duration and related continuation rules

Continued approval durationContinued therapy approvals for chronic indications are granted for 12 months.

Continuation requirementsContinuation requires documentation of ongoing clinical response as specified per indication (e.g., LDH for PNH, ≥2-point MG-ADL reduction for gMG, improved/stable EDSS for NMOSD).

Dose increase and maximumsIf a dose increase is requested, the new dose must not exceed indication-specific maximums (PNH: 900 mg q2w; aHUS: 1200 mg q2w; gMG/NMOSD: 1200 mg q2w).

Diagnostic test expectations vary by indication and must be included in initial authorization requests. For PNH, flow cytometry demonstrating detectable glycosylphosphatidylinositol (GPI)-deficient hematopoietic clones or ≥10% PNH cells is required. For gMG, document MG-ADL score at baseline and anti-AChR serology if positive; MGFA clinical classification (Class II–IV) should be recorded. For NMOSD, document anti-AQP4 antibody (AQP4-IgG) serostatus using a validated cell-binding assay and baseline EDSS score. For aHUS, include platelet count, evidence of thrombotic microangiopathy (e.g., elevated LDH, hemolysis), serum creatinine and ADAMTS13 to exclude deficiency.

PNH: flow cytometry report showing GPI-deficient clone percentage (≥10% threshold).
gMG: baseline MG-ADL total score, MGFA class, and anti-AChR antibody test result.
NMOSD: anti-AQP4 antibody (cell-based assay) result and baseline EDSS score.
aHUS: platelet count, LDH, serum creatinine, documentation excluding ADAMTS13 deficiency and STEC-HUS.

Documentation Required

Provider action: Clinical response and biomarker documentation

Clinical response and biomarker documentation must be provided for continuation requests and to demonstrate efficacy. Examples of acceptable response measures include stabilization or improvement in condition-specific markers: for PNH — reduced LDH, fewer transfusions, improved hemoglobin and clinical symptoms; for gMG — ≥2-point reduction in MG-ADL score is considered clinically meaningful; for aHUS — normalization of platelet count and LDH, reduced need for plasma therapy or dialysis, improved GFR; for NMOSD — stabilization or reduction in EDSS and relapse frequency. For AQP4 serostatus, document commercial cell-based assay results.

Include baseline and most recent values for LDH, hemoglobin, transfusion frequency (PNH).
Provide baseline and follow-up MG-ADL scores and clinical notes documenting functional change (gMG).
Provide platelet count, LDH, creatinine/GFR trends and dialysis dependence status (aHUS).
Document relapses, EDSS trend, and AQP4-IgG results (NMOSD).

Step Therapy

Provider action: Step therapy requirements / Step therapy sequence

Step therapy and sequencing requirements differ by indication. For gMG, member must have failed a qualifying immunosuppressive therapy (now clarified to one non-steroidal immunosuppressive agent unless contraindicated) and failed a corticosteroid unless contraindicated; MG-related step edits may be subject to state-specific exceptions (e.g., Illinois HB 5395). For NMOSD, member must have failed rituximab at maximally indicated doses (preferred products: Ruxience and Truxima; Truxima and Ruxience specified), with prior authorization generally required for rituximab products. Historically, stepwise redirection requirements (e.g., redirection to Enspryng if rituximab failed) were implemented and later removed; current policy requires failure of rituximab before eculizumab but no mandatory redirection to Enspryng.

gMG: document trial and failure (or contraindication) of corticosteroid and one non-steroidal immunosuppressive agent unless state law exempts step edits.
NMOSD: document trial and inadequate response or intolerance to rituximab (preferred biosimilars noted); prior authorization for rituximab products may be required.
Be aware of state-specific mandates (e.g., IL) that may override step therapy requirements.

Documentation Required

Provider action: Continuation and supplemental dosing documentation

Continuation and supplemental dosing documentation — For continuation requests, provide evidence of ongoing clinical benefit per the response measures above. Continuation approvals were revised to longer durations for chronic conditions (continued approval duration updated to 12 months per recent review). Supplemental dosing or additional doses may be approved when the member is receiving plasmapheresis, plasma exchange, fresh frozen plasma infusion, or IVIg; for gMG specifically, supplemental eculizumab dosing is required in the setting of concomitant IVIg. Continuity-of-care allowances have been extended to cover Bkemv and Epysqli for continuation requests.

Continuation requests must include documentation of clinical benefit (see Clinical response and biomarker documentation).
If the member is receiving plasmapheresis/plasma exchange/FFP/IVIg, submit timing of procedures and rationale for supplemental dosing per Appendix E.
Note updated continued approval duration: 12 months for chronic indications (per 3Q 2025 review).

Note

Provider action: Step-therapy history for NMOSD

Step-therapy history for NMOSD — Policy history included a period where, after rituximab failure, members were required to be redirected to Enspryng prior to eculizumab; this redirection requirement was later removed. Current policy requires failure of rituximab (preferred biosimilars noted) prior to consideration of eculizumab, but does not mandate Enspryng as an intermediate step. Providers should document prior rituximab regimen, doses, dates, and rationale for discontinuation or failure.

Document rituximab product used (e.g., Rituxan, Ruxience, Truxima, Riabni) and dosing regimen (induction: 375 mg weekly x4; maintenance per product regimen).
If rituximab was not used or was discontinued for intolerance, document reasons and supporting clinical notes.

Abbreviation contextaHUS is included in the abbreviation appendix as atypical hemolytic uremic syndrome.

MG-ADL — definition and policy use

Definition: MG-ADLMG-ADL: Myasthenia Gravis-Activities of Daily Living (used as a baseline and response measure in gMG criteria).

Usage in policyMG-ADL score ≥6 required at baseline for initiation; ≥2-point reduction used to document response for continuation.

Appendix listingMG-ADL appears in the policy abbreviation appendix alongside other clinical scales (MGFA, EDSS).

EDSS — definition and policy use

Definition: EDSSEDSS: Expanded Disability Status Scale (baseline EDSS <7 required for NMOSD initial approval).

NMOSD usageBaseline EDSS score <7 is an explicit requirement for NMOSD initial approval in the policy.

Appendix listingEDSS is included in the policy abbreviation appendix for clinical scoring reference.

aHUS — terminology

aHUS (terminology)aHUS: atypical hemolytic uremic syndrome.

Management guidancePolicy references international consensus management guidance for aHUS diagnostics and monitoring.

Abbreviation entryaHUS appears in the policy abbreviation appendix as atypical hemolytic uremic syndrome.

PNH — terminology

PNH (terminology)PNH: paroxysmal nocturnal hemoglobinuria.

Diagnostic referencesPolicy cites literature for diagnosis and management of PNH (see referenced works in appendices).

Abbreviation entryPNH included in abbreviation appendix as paroxysmal nocturnal hemoglobinuria.

PNH — full reference

PNH: formal name and sourcesPNH: Paroxysmal nocturnal hemoglobinuria; policy references diagnostic and management literature (Parker et al.).

Clinical contextPNH definitions and management sources are provided to support diagnostic flow-cytometry requirements in the policy.

Appendix listingPNH appears in the abbreviation appendix for quick reference.

aHUS — references and guidance

aHUS: formal name and guidanceaHUS: Atypical hemolytic uremic syndrome; policy references international consensus management guidance (Loirat et al., other reviews).

Supporting literatureMultiple guideline and review citations are listed to support diagnostic and monitoring recommendations for aHUS.

Appendix listingaHUS included in the abbreviation appendix for clinician reference.