ModifiedHealth NetPolicy CP PHAR.97

Eculizumab (Soliris) and biosimilars (Bkemv, Epysqli) — coverage criteria

Policy governing medical necessity criteria, prior authorization, and continued use for eculizumab (Soliris) and biosimilars (Bkemv, Epijkstra) across covered lines of business; affects providers prescribing these agents for PNH, aHUS, gMG, NMOSD, and other indications for Health Net/Centene products.

Policy Summary

PayerHealth Net

PolicyEculizumab (Soliris), Bkemv, Epijkstra — coverage criteria

Policy CodePolicy CP PHAR.97

Change TypeMaterial updates: biosimilars addedcontinued approval extendedconcurrent therapy list revised

Effective Date03.01.12

Next Review Date

Key ActionSubmit prior authorization with supporting clinical documentation demonstrating all applicable criteria are met.

SourceLink

POLICY UPDATE CHANGES

Added newly approved biosimilar Bkemv.

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

Updated list of therapies that Soliris/Bkemv/Epijkstra should not be prescribed concurrently with, adding multiple products including Rystiggo, Vyvgart Hytrulo, Zilbrysq, Fabhalta, Ultomiris, and later PiaSky.

Revised continued approval duration from 6 to 12 months for all indications.

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

4FDA-approved primary indications listed

6 moInitial approval duration

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Coverage Criteria and Clinical Rules

Initial Therapy — 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 demonstrating detectable GPI-deficient hematopoietic clones or ≥10% PNH cells. 4. Age criteria met as specified in the product labeling. 5. Member meets ONE of the following: (a) History of ≥1 red blood cell transfusion in the past 24 months AND either (i) hemoglobin <7 g/dL if asymptomatic OR (ii) hemoglobin <9 g/dL if symptomatic; OR (b) history of thrombosis. 6. Medication is not prescribed concurrently with Empaveli, Fabhalta, PiaSky, or Ultomiris unless the member is in a ≤4‑week cross‑titration period. 7. Dosing does not exceed 600 mg per week for the first 4 weeks, followed by 900 mg for the fifth dose one week later, then 900 mg every 2 weeks thereafter.see text

Approval duration: 6 months

Initial Therapy — aHUS

Covered when ALL of the following are met:

aHUS initial: 1. Diagnosis of atypical hemolytic uremic syndrome (complement‑mediated HUS). 2. Prescribed by or in consultation with a hematologist or nephrologist. 3. Age ≥ 2 months. 4. Platelet count <150 × 10^9/L. 5. Evidence of thrombotic microangiopathy (TMA) including hemolysis such as elevated LDH and serum creatinine above the upper limits of normal or need for dialysis. 6. Documentation that the member does NOT have ADAMTS13 deficiency or STEC‑HUS. 7. Medication is not prescribed concurrently with Ultomiris. 8. Dosing does not exceed the age‑based FDA maximum (for adults: 900 mg weekly ×4 then 1,200 mg for the fifth dose one week later, then 1,200 mg every 2 weeks).see text

Additional doses may be approved during concomitant plasmapheresis/plasma exchange/FFP; Approval duration: 6 months

Initial Therapy — 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–IV. 5. Baseline MG‑ADL score ≥6. 6. Positive anti‑AChR antibody serology. 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. Medication is not prescribed concurrently with Rystiggo, Ultomiris, Vyvgart, Vyvgart Hytrulo, or Zilbrysq. 11. Dose limits per FDA labeling (example adult induction: 900 mg weekly ×4 then 1,200 mg for the fifth dose one week later then 1,200 mg every 2 weeks).MG-ADL >=6

Approval duration: 6 months

Initial Therapy — 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 serology. 5. Either: (a) history of ≥2 relapses in the prior 12 months OR (b) history of ≥3 relapses in the prior 24 months with at least one relapse in the past 12 months. 6. Baseline EDSS score <7. 7. Failure of rituximab at maximally indicated doses unless contraindicated. 8. Medication is not prescribed concurrently with rituximab, Enspryng (Uplizna), or Ultomiris. 9. Dose does not exceed 900 mg weekly ×4 then 1,200 mg for the fifth dose one week later then 1,200 mg every 2 weeks thereafter.see text

Approval duration: 6 months

Continued Therapy

Criteria for continued therapy and renewal logic:

Continued therapy general: 1. Member is currently receiving the medication via the benefit or previously met initial approval criteria. 2. Member is responding positively to therapy as evidenced by indication‑specific improvement: PNH — improved intravascular hemolysis (e.g., normalization of LDH), reduced RBC transfusion requirement, increased or stable hemoglobin, reduced fatigue, fewer thrombotic events, improved health‑related quality of life; aHUS — normalization of LDH, increased/stable platelet count, improved or stabilized serum creatinine/eGFR, reduced need for dialysis; gMG — ≥2‑point reduction in MG‑ADL from baseline; NMOSD — improvement or stabilization in EDSS, relapse frequency, or visual acuity. 3. Medication is not prescribed concurrently with disallowed agents for the specific indication (e.g., PNH: Empaveli, Fabhalta, PiaSky, Ultomiris; aHUS: Ultomiris; gMG: Rystiggo, Ultomiris, Vyvgart, Vyvgart Hytrulo, Zilbrysq; NMOSD: rituximab, Enspryng/Uplizna, Ultomiris). 4. If request is for a dose increase, new dose must not exceed indication‑specific maximums (PNH: 900 mg every 2 weeks; aHUS: 1,200 mg every 2 weeks; gMG/NMOSD: 1,200 mg every 2 weeks).

Approval duration for continued therapy: 12 months

Continuity of care: Member currently receiving medication and enrolled in a state/product with continuity of care regulations may continue therapy per state addenda.

Approval duration: 12 months

Other Indications / Off-label handling

Handling of other/ off‑label indications and formulary considerations:

Other indications handling: 1. If the requested indication is on the formulary/PDL, follow the no‑coverage‑criteria policy for the applicable line of business (e.g., CP.CPA.190 commercial, HIM.PA.33 marketplace, CP.PMN.255 Medicaid). 2. If the drug is NOT on the formulary/PDL, follow the non‑formulary policy for the applicable line of business (e.g., CP.CPA.190 commercial, HIM.PA.103 marketplace, CP.PMN.16 Medicaid). 3. If the requested use is not listed in section III and criterion 1 above does not apply, refer to the off‑label use policy for the relevant line of business (CP.CPA.09 commercial, HIM.PA.154 marketplace, CP.PMN.53 Medicaid).

If the drug label has changed within the last 6 months and this policy is not updated, refer to the specified formulary/non‑formulary policies.

Covered indications (listed in document)

Covered indications listed in the policy (coverage requires meeting the indication‑specific criteria elsewhere in this document):

Covered indications: PNH; aHUS (complement‑mediated HUS); generalized myasthenia gravis (AChR antibody positive); neuromyelitis optica spectrum disorder (AQP4‑IgG seropositive).

Dosing regimens and indication‑specific requirements are provided in the Dosage and Administration and Initial/Continued criteria sections.

Dose adjustment during plasmapheresis/IVIg

Supplemental dosing guidance during extracorporeal therapies or frequent IVIg:

Supplemental dosing rules: Provide supplemental eculizumab dosing when the patient undergoes plasmapheresis/plasma exchange or receives fresh frozen plasma per the table in Appendix E: e.g., if most recent eculizumab dose = 300 mg, give 300 mg supplemental per plasmapheresis session; if most recent dose = 600 mg, give 600 mg supplemental per session; fresh frozen plasma infusion: 300 mg supplemental per infusion; IVIg: supplemental dosing rules vary by frequency and most recent eculizumab dose as specified (no supplemental dose for some acute IVIg rescue scenarios; 300–600 mg adjustments for frequent IVIg per Appendix E).

See Appendix E and the detailed table for per‑intervention mg amounts and timing.

Coverage updates and restrictions

Recent coverage updates, restrictions, and utilization management clarifications:

Concurrent therapy restriction: Eculizumab products (Soliris, Bkemv, Epinnaq/Epigslist) should not be prescribed concurrently with listed therapies: for gMG — Rystiggo, Vyvgart, Vyvgart Hytrulo, Zilbrysq; for PNH — Fabhalta, Empaveli, PiaSky; for NMOSD — Ultomiris, rituximab, Enspryng/Uplizna. Exceptions may be allowed for limited cross‑titration periods as specified in the policy.

Continuation of therapy duration: Continued approval duration for chronic indications revised from 6 months to 12 months for continuing therapy requests.12 months

Applies to continued therapy and continuity of care allowances, including for biosimilars.

gMG immunosuppressive therapy requirement: For generalized myasthenia gravis (gMG), required adjunct immunosuppressive therapy must be non‑steroidal (i.e., non‑steroidal immunosuppressants are required when specified).

Clarified in 3Q 2025 review.

Coverage is NOT authorized for the following diagnoses: STEC-HUS (Shiga toxin–producing E. coli–associated HUS); antiphospholipid syndrome (ICD-10: D68.61); and unspecified nephritic syndrome with other morphologic changes (ICD-10: N0S.8). In addition, uses that are non‑FDA approved and are not addressed by this policy are excluded unless the request includes sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (CP.CPA.09, HIM.PA.154, CP PMN.53) or other evidence-of-coverage documents.

The policy considers certain indications investigational and therefore excluded from coverage due to lack of conclusive, randomized controlled trial evidence. Examples called out in the policy include unspecified nephritic syndrome with other morphologic changes; when an indication is considered investigational, conventional therapies (for example, immunosuppression such as prednisone or mycophenolate mofetil) are listed as alternatives. Requests for non‑FDA indications will be handled per the off‑label use policies referenced above and may be denied if supporting evidence is insufficient.

The policy includes explicit restrictions on concurrent therapy: eculizumab (Soliris) and its biosimilars should not be prescribed concurrently with a growing list of targeted therapies across indications (examples include Ultomiris, Fabhalta, Rystiggo, Vyvgart/Vyvgart Hytrulo, Zilbrysq, PiaSky and others). These restrictions have evolved over time — earlier reviews first added Ultomiris to the prohibition for PNH and aHUS and later updates expanded the list to include additional agents and biosimilars. Providers should note limited exceptions for brief cross‑titration periods where specified in the criteria.

Specific uses that are not authorized include STEC-HUS and other indications the policy designates as investigational. The policy further requires supplemental dosing in the setting of extracorporeal therapies or frequent IVIg — for aHUS, gMG, and NMOSD, supplemental eculizumab doses are required when plasmapheresis, plasma exchange or fresh frozen plasma infusions are given. Where an indication is considered investigational, alternative, evidence‑based therapies are recommended.

Uses listed as investigational/not covered are those lacking conclusive randomized controlled trial data in the body of evidence. The policy explicitly states that Soliris/Bkemv/Epysqli for certain indications (for example, unspecified nephritic syndrome with other morphologic changes) is considered investigational; such requests are managed according to off‑label policies and may be denied when evidence is insufficient.

Policy history documents prior restrictions on concurrent use: early updates prohibited concurrent prescribing with Ultomiris for PNH and aHUS, and subsequent reviews expanded the prohibited list and clarified cross‑titration exceptions. Recent reviews also added biosimilars (Bkemv, Epysqli) to continuity‑of‑care and concurrent‑use language and adjusted billing code references; providers should review the concurrently prohibited agents when submitting prior authorization requests.

Codes, Thresholds, and Dose Notes

Policy identifiers and drug namesmixed

No codes listed

Explicit non-covered ICD-10 codesICD-10Not Covered

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

HCPCS/HCPCS-like 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 then removed per later update
J1300	HCPCS code removed per update
J3590	Code removed per earlier update
C9399	Code removed per earlier update

inv-19: Hemoglobin and laboratory thresholds — lab cutoffs and testing requirements

Hemoglobin thresholds for PNHDocumentation of hemoglobin <7 g/dL in members without anemia symptoms or <9 g/dL in members with anemia symptoms (when history of >=1 RBC transfusion in past 24 months is present)

Flow cytometry requirementFlow cytometry showing detectable GPI-deficient hematopoietic clones or ≥10% PNH cells is required to confirm PNH diagnosis

aHUS platelet and hemolysis criteriaFor aHUS, platelet count <150 x10^9/L plus evidence of hemolysis (elevated LDH) and other TMA features are required

MG baseline score thresholdFor gMG, baseline MG-ADL score ≥6 is required

NMOSD EDSS thresholdFor NMOSD, baseline Expanded Disability Status Scale (EDSS) score must be <7

Provider Actions, Prior Authorization, and Billing

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit clinical documentation (office chart notes, lab results, serologic test results, MG-ADL or EDSS scores, prior therapy records, and other relevant information) to support that the member meets all approval criteria. Refer to formulary and off‑label use policies for line-of-business specifics: CP.CPA.190 (commercial), HIM.PA.154 / HIM.PA.103 (health insurance marketplace), and CP.PMN.255 / CP.PMN.16 / CP.PMN.53 (Medicaid) as applicable.

Prior authorization required with supporting documentation (office notes, labs, serology, baseline scores).
Refer to formulary/non‑formulary/off‑label policies for coverage determination per line of business: CP.CPA.190, HIM.PA.154, HIM.PA.103, CP.PMN.255, CP.PMN.16, CP.PMN.53.

Denial Risk

Explicit Noncoverage

Requests for the following diagnoses/uses are not authorized under this policy: STEC‑HUS; antiphospholipid syndrome (D68.61); unspecified nephritic syndrome with other morphologic changes (N0S.8); and other non‑FDA indications not addressed in this policy unless sufficient documentation per off‑label policies or evidence of coverage is provided.

Background and Clinical Context

Eculizumab and biosimilars are complement C5 inhibitors used to reduce intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) and to inhibit complement‑mediated thrombotic microangiopathy in atypical hemolytic uremic syndrome (aHUS). They are also approved for neurologic autoimmune conditions in selected, antibody‑positive patients — specifically generalized myasthenia gravis (AChR antibody positive) and neuromyelitis optica spectrum disorder (AQP4‑IgG seropositive). The policy reflects this mechanism and clinical context and ties coverage to indication‑specific diagnostic and laboratory criteria (for example, flow cytometry for PNH, platelet count and LDH for aHUS, anti‑AChR or anti‑AQP4 antibody testing and functional scores for neurologic indications), REMS‑related vaccination requirements, and supplemental dosing rules when extracorporeal therapies or IVIg are used.

Definitions and Abbreviations

inv-34: paroxysmal nocturnal hemoglobinuria (PNH) — definition entry

DefinitionParoxysmal nocturnal hemoglobinuria (PNH): a hematologic disorder listed and abbreviated in the policy as PNH; diagnosis supported by flow cytometry for GPI-deficient clones

Diagnostic testFlow cytometry demonstrating detectable glycosylphosphatidylinositol (GPI)-deficient hematopoietic clones or ≥10% PNH cells

Typical clinical criteria in policyPolicy requires hematology consultation and criteria such as history of RBC transfusion or thrombosis for treatment eligibility

inv-35: atypical hemolytic uremic syndrome (aHUS) — definition entry

DefinitionAtypical hemolytic uremic syndrome (aHUS): complement-mediated HUS referenced in the policy as aHUS

Diagnostic exclusions

Policy Summary

PayerHealth Net

PolicyEculizumab (Soliris), Bkemv, Epijkstra — coverage criteria

Policy CodePolicy CP PHAR.97

Change TypeMaterial updates: biosimilars addedcontinued approval extendedconcurrent therapy list revised

Effective Date03.01.12

Next Review Date

Key ActionSubmit prior authorization with supporting clinical documentation demonstrating all applicable criteria are met.

SourceLink

On This Page

inv-20: Supplemental dosing allowance — extra doses when plasmapheresis/IVIg ongoing

Supplemental dosing allowance (general)Additional doses of eculizumab may be approved when the member is receiving plasmapheresis, plasma exchange, or fresh frozen plasma infusion; see Appendix E for specifics

aHUS-specific notePolicy explicitly states additional doses may be approved in the setting of concomitant plasmapheresis/plasma exchange/FFP for aHUS

NMOSD and gMG supplemental dosingDocumented asterisk in dosing sections notes that additional doses may be approved for NMOSD and gMG if extracorporeal therapies or IVIg are given

Documentation Required

Vaccination and REMS Documentation

Because these agents are available only through a REMS for risk of meningococcal infection, document meningococcal vaccination status and REMS enrollment in the prior authorization request. Patients should be vaccinated at least 2 weeks before the first dose and revaccinated per current guidelines; monitor and document counseling about signs of meningococcal infection and emergency evaluation plans.

Document meningococcal vaccination dates and manufacturer where available.
Document REMS enrollment and that patient counseling/monitoring plans were provided.
Vaccinate at least 2 weeks prior to first dose and follow ACIP guidance for revaccination.

Billing Rule

Coding and Billing Documentation Note

Providers should reference current coding guidance when submitting claims. The policy lists HCPCS/CPT changes historically for information only; confirm up‑to‑date HCPCS/CPT/NDC codes prior to billing.

HCPCS updates noted historically (examples): Q5139, J1299, Q5151, Q5152; codes J3590 and C9399 were removed. Verify current codes before billing.
This policy's code listings are informational; use payer billing guidance for final code selection.

Step Therapy

Step Therapy Requirements

Step therapy requirements apply per indication. For gMG: diagnosis and baseline MG‑ADL ≥6, positive anti‑AChR antibodies, prescribed by or in consultation with a neurologist, age criteria, and failure of a corticosteroid (unless contraindicated) and at least one non‑steroidal immunosuppressive therapy as required by the current criteria. For NMOSD: diagnosis, positive anti‑AQP4 antibodies or documented relapse history per criteria, prescribed by or in consultation with a neurologist, age criteria, and failure of rituximab (preferred biosimilars listed) unless contraindicated. Note: for Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

gMG step requirements: diagnosis of gMG, neurologist involvement, age per criteria, MG‑ADL ≥6, positive anti‑AChR, failure of corticosteroid, and required non‑steroidal immunosuppressive therapy.
NMOSD step requirements: diagnosis of NMOSD, neurologist involvement, age ≥18, positive anti‑AQP4 or qualifying relapse history, failure of rituximab (preferred products: Ruxience, Truxima, others) unless contraindicated.
Illinois HIM exception: step therapy requirements waived effective 01/01/2026 per IL HB 5395.

Note

Therapeutic Alternatives / Sequencing

Therapeutic alternatives and sequencing should be documented in the PA request. Preferred alternatives include corticosteroids, cholinesterase inhibitors, immunosuppressants (azathioprine, mycophenolate mofetil, cyclosporine), and rituximab products (Rituxan and biosimilars Ruxience, Truxima, Riabni, etc.) where indicated. Prior authorization may be required for rituximab products.

List of alternatives commonly considered: corticosteroids (prednisone, methylprednisolone), cholinesterase inhibitors (pyridostigmine), immunosuppressants (azathioprine, mycophenolate mofetil, cyclosporine).
Rituximab and biosimilars (Rituxan, Ruxience, Truxima, Riabni) are therapeutic alternatives for NMOSD and may require prior authorization.
Document prior trials, doses, durations, and reasons for failure or intolerance to alternatives.

inv-41: PNH / aHUS / NMOSD — grouped reference to primary disease areas

Primary disease areasPolicy addresses paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and neuromyelitis optica spectrum disorder (NMOSD) as principal indications

Cross‑indication referencesDosing, discontinuation, and concurrent therapy restrictions are specified per condition across the policy

Related definitionsPNH, aHUS, and NMOSD are also listed together in the appendices and cited literature sections