Blue Cross MA complement inhibitors Prior Auth Update

Coverage Criteria

inv-01: Initial Therapy / Indication-specific criteria

Covered when ALL of the following are met for each indication group

PNH (Paroxysmal nocturnal hemoglobinuria): Confirmed diagnosis of PNH; documented baseline serum lactate dehydrogenase (LDH) >= 2.5 times the upper limit of normal; age 18 years or older (agent-specific age exceptions noted elsewhere); no dual therapy with another terminal complement inhibitor (e.g., ravulizumab, pegcetacoplan, biosimilar eculizumab products, or Soliris); vaccination against Neisseria meningitidis, pneumococcus, and H. influenzae prior to initiation unless treatment cannot be delayed; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

Atypical hemolytic uremic syndrome (aHUS): Documented diagnosis of aHUS; documented baseline LDH (unless the patient has been receiving plasma exchange) per policy requirements; does not have Shiga toxin E. coli–related HUS (STEC‑HUS); no dual therapy with another terminal complement inhibitor; vaccination against Neisseria meningitidis, pneumococcus, and H. influenzae prior to initiation unless treatment cannot be delayed; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

Generalized myasthenia gravis (gMG): Positive serologic test for anti‑AChR antibodies (or MuSK antibodies for specified agents where applicable); Myasthenia Gravis Foundation of America (MGFA) Clinical Classification II–IV; age 18 years or older (some agents allow age >=6 or other agent‑specific age criteria); documented baseline MG‑Activities of Daily Living (MG‑ADL) total score above the agent‑specific threshold (policy cites >6 for some agents or >5 for others); vaccination against Neisseria meningitidis, pneumococcus, and H. influenzae prior to initiation unless treatment cannot be delayed; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency; for Soliris in adults, trial and failure of or contraindication to Vyvgart or Vyvgart Hytrulo is required.

Neuromyelitis optica spectrum disorder (NMOSD): Confirmed diagnosis of NMOSD with positive anti‑AQP4 antibody; age 18 years or older; vaccination against Neisseria meningitidis, pneumococcus, and H. influenzae prior to initiation unless treatment cannot be delayed; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

C3 glomerulopathy (C3G) and IgA nephropathy (IgAN) when applicable: Documented diagnosis of C3G or primary IgA nephropathy per policy‑specified indications (e.g., for Fabhalta); age and laboratory thresholds (such as UPCR or other lab criteria) as specified in the policy; vaccination and REMS enrollment as applicable; no dual therapy with another terminal complement inhibitor; documented dose and frequency within FDA‑approved dosing and frequency.

inv-02: Continuation Therapy

Continuation of therapy is approved when ALL of the following are met

PNH continuation: Confirmed diagnosis of PNH; demonstrated decrease in serum LDH from pretreatment baseline; age 18 years or older; no dual therapy with another terminal complement inhibitor; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

aHUS continuation: Documented decrease in LDH from pretreatment baseline; absence of Shiga toxin E. coli–related HUS (STEC‑HUS); no dual therapy with another terminal complement inhibitor; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

gMG continuation: Demonstrated decrease in MG‑ADL total score from baseline (or other measure such as fewer relapses for NMOSD as applicable); age 18 years or older; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

Medications named in this policy are restricted to the specific conditions and indications described in the criteria. We do not cover the medications listed above for conditions not listed above.

Requests for non-formulary or non-covered medications must meet the applicable policy criteria and, when formulary alternatives exist, the member must have had a prior treatment failure with or a documented contraindication to two covered formulary alternatives. If these requirements are not met, the request is not covered.

Initial Therapy Examples by Agent and Indication

inv-20: Initial therapy examples

Agent- and indication-specific initial criteria (examples):

Soliris/Ultomiris for PNH: Confirmed diagnosis of PNH; documented baseline LDH >= 2.5x ULN; age criteria per agent (Soliris: age >=18; Ultomiris: may include age >=1 month); vaccination against Neisseria meningitidis, pneumococcus, and H. influenzae prior to initiation unless treatment cannot be delayed; no dual therapy with another terminal complement inhibitor; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

Fabhalta for C3G or IgAN (example): Documented diagnosis of C3G or primary IgA nephropathy where policy allows Fabhalta; age and lab criteria as specified in the policy (e.g., UPCR thresholds where applicable); vaccination and REMS enrollment as applicable; no dual therapy with another terminal complement inhibitor; documented dose and frequency within FDA‑approved dosing and frequency.

Vyvgart/Vyvgart Hytrulo for gMG: Positive anti‑AChR serology; MGFA Class II–IV; documented baseline MG‑ADL above agent‑specific threshold (policy lists >5 for some agents and >6 for others); age 18 years or older (agent‑specific exceptions apply); prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

Continuation Criteria Examples

inv-21: Examples of continuation rules

Continuation requirements vary by drug and indication; examples below.

Empaveli continuation (example): Confirmed diagnosis of PNH; decrease in serum LDH from pretreatment baseline; age 18 years or older; no dual therapy with another terminal complement inhibitor; prescribing physician enrolled in REMS program if available; documented dose and frequency within FDA‑approved dosing and frequency.

General continuation operational rule: For continuation across agents/indications: documented clinical improvement (e.g., reduced LDH for hemolytic indications, reduced MG‑ADL for gMG, or fewer relapses for NMOSD), age criteria met, no concurrent dual terminal complement inhibitor therapy, REMS enrollment if available, and documented dose and frequency within FDA‑approved dosing and frequency.

Coding and Clinical Thresholds

HCPCS CodesHCPCS

Q5152
Q5151	Epysqlie (eculizumab-aagb)
J1299	Injection, eculizumab (Soliris-originator) 2 mg
J1823	Injection, inebilizumab-cdon (UPLIZNA)
J1300	Injection, eculizumab, 10 mg (Soliris)
J1303
J3590
C9399	Not otherwise Classified Code (Empaveli)
J9333	Injection, rozanolixizumab (Rystiggo)
J9334	Injection, efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo)

HCPCS (updated)HCPCS

HCPCS updated

Policy history notes HCPCS codes were updated; specific updated code list referenced in policy history entry dated 4/2025.

inv-07: LDH baseline

LDH baseline requirementDocumented baseline serum lactate dehydrogenase (LDH) ≥ 2.5 times the upper limit of normal (documented baseline LDH 2.5x ULN).

Age requirement (PNH)18 years of age or older for PNH (agent-specific age exceptions noted elsewhere).

Dual-therapy restrictionNo dual therapy with another terminal complement inhibitor (temporary 4‑week overlap permitted when switching to Empaveli).

inv-08: MG-ADL baseline

MG-ADL baseline threshold (Soliris, some agents)Documented baseline MG‑Activities of Daily Living (MG‑ADL) total score > 6 (required for Soliris and specified agents).

MG-ADL baseline threshold (Vyvgart Hytrulo etc.)

Provider Actions, Submission & Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for listed biologics. If approved, prior authorization may be granted for up to one (1) year. Outpatient retail pharmacy requests and other PA requests must follow the submission instructions below.

If approved, the Prior Authorization will be granted for up to one (1) year.
Pharmacy (Rx) vs Medical (MED) benefit: some products are pharmacy-only; others are under the medical benefit. Refer to the formulary chart for benefit assignment.

Documentation Required

Prior Authorization Submission Requirement

Prior authorization requests must be submitted using the Massachusetts Standard Form for Medication Prior Authorization Requests (eForm) or by printing and faxing the Massachusetts Standard Form for Medication Prior Authorization Requests #434. For pharmacy prior authorization contact information, see Blue Cross Blue Shield of Massachusetts Pharmacy Operations.

Step Therapy and Prior Treatment Documentation

Requirement	Acceptable documentation
Prior use of formulary alternatives (required failure or contraindication when applicable)
Documentation may be established via prescription claims records showing previous fills for formulary alternatives
Provider-submitted clinical records when claims data are unavailable or insufficient (e.g., chart notes, treatment history specifying drug name, dose, dates, and reason for discontinuation)

Site of Care

Billing Rule

Confirm site‑of‑care and benefit (medical vs pharmacy) before submitting PA

Most listed agents are covered under the medical benefit; one drug in the chart is covered only under the pharmacy benefit — verify benefit assignment and submit authorization via the appropriate channel (medical prior authorization vs. Pharmacy Operations).

Chart indicates one drug is pharmacy‑only; all others are medical benefit with PA required.
Outpatient retail pharmacy requests should be directed to BCBSMA Pharmacy Operations.

Biosimilars

Billing Rule

Soliris and biosimilars: formulary with PA required

Soliris (eculizumab) and its biosimilars (Epysqlie, Bkemv) are listed as formulary with prior authorization required; biosimilars were added to the policy in the 4/2025 update.

Soliris (eculizumab) — PA Required per formulary chart.
Biosimilars Epysqlie and Bkemv added to policy history (4/2025) and require PA.

Billing Rule

Epysqlie (biosimilar) added to policy — include product name on PA

Epysqlie was added to the policy as a biosimilar and is referenced in the policy history and references; providers should include the specific product name in PA requests to align with updated HCPCS and policy entries.

Policy history (4/2025) lists Epysqlie addition.
Package insert reference for Epysqlie appears in the References section.

Billing Rule

Background

Complement inhibitors (for example, eculizumab, ravulizumab, pegcetacoplan) and related specialty biologics are used to treat rare complement-mediated disorders including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), neuromyelitis optica spectrum disorder (NMOSD), complement 3 glomerulopathy (C3G), and chronic inflammatory demyelinating polyneuropathy (CIDP). Prior to initiation and for continuation, the policy requires condition-specific documentation such as confirmed diagnosis, baseline laboratory or clinical scores (for example, baseline LDH ≥ 2.5× ULN for PNH or baseline MG‑ADL thresholds for gMG), appropriate serologic testing when indicated (eg, anti‑AChR, MuSK, or AQP4), vaccination and REMS enrollment where applicable, and adherence to FDA‑approved dosing and frequency.

Definitions

inv-18: PNH — Paroxysmal nocturnal hemoglobinuria (PNH)

TermParoxysmal nocturnal hemoglobinuria (PNH).

Key diagnostic requirementConfirmed diagnosis of PNH is required for coverage of PNH indications.

Associated lab requirementDocumented baseline LDH ≥ 2.5x ULN for PNH initiation; decrease in LDH from pretreatment baseline for continuation.

inv-19: gMG — Generalized myasthenia gravis (gMG) with MG-ADL scoring and MGFA clinical classification used for eligibility

ConditionGeneralized myasthenia gravis (gMG).

Serology requirementPositive serologic test for anti‑AChR antibodies (MuSK antibodies acceptable for some agents such as rozanolixizumab).

Revision History

2025-04material_updateLatest

Updated criteria to add biosimilars Epysqlie and Bkemv, cleaned up formatting, updated HCPCS codes, and added expanded indications for Fabhalta (C3G) and Soliris (gMG ages 6 and up).

2025-01material_update

Added Vyvgart Hytrulo and new indications for Fabhalta.

2024-07material_update

Added Zilbrysq to the policy and clarified coverage criteria.

OpenPayer

Soliris, Ultomiris and Related Complement Inhibitors — Pharmacy Medical Policy

Coverage Criteria

Initial Therapy Examples by Agent and Indication

Continuation Criteria Examples

Coding and Clinical Thresholds

Provider Actions, Submission & Documentation Requirements

Step Therapy and Prior Treatment Documentation

Site of Care

Biosimilars

Background

Definitions

Revision History