Centene pegcetacoplan Coverage Update

Coverage Criteria for Pegcetacoplan (Empaveli, Syfovre)

Initial Approval — Paroxysmal Nocturnal Hemoglobinuria (PNH)

Covered when ALL of the following are met:

PNH initial criteria: 1) Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH); 2) Request is for Empaveli (pegcetacoplan); 3) Prescribed by or in consultation with a hematologist; 4) Age >= 18 years; 5) Flow cytometry demonstrates detectable GPI-deficient hematopoietic clones >= 10% PNH cells; 6) Documentation of hemoglobin <= 10.5 g/dL; 7) Empaveli is not prescribed concurrently with Syfovre or another FDA‑approved product for PNH (e.g., Soliris, Ultomiris, Fabhalta, Voydeya, Bkemv, Epysqli, PiaSky) unless the member is within an allowed cross‑titration/switching period (provider must attest to presence/absence of concomitant therapy and follow cross‑titration guidance); 8) Dose does not exceed 2,160 mg per week or 1,080 mg every 3 days (total 10 doses per month) with documentation of LDH > 2x ULN when dosing at the upper limit; 9) Provider submits clinical documentation supporting diagnosis and criteria fulfillment

Approval duration: 6 weeks if within cross‑titration with Soliris/Bkemv/Epijkstra (initiate Empaveli while continuing prior therapy and discontinue prior therapy after 4 weeks) otherwise 6 months; continued approval duration for chronic PNH revised to 12 months (see continued therapy criteria).

Initial Approval — C3 Glomerulopathy (C3G) or Primary IC‑MPGN

Covered when ALL of the following are met:

C3G/IC‑MPGN initial criteria: 1) Diagnosis of C3 glomerulopathy (C3G) or primary immune‑complex membranoproliferative glomerulonephritis (primary IC‑MPGN) confirmed by kidney biopsy (not recurrent post‑transplant); 2) Request is for Empaveli (pegcetacoplan); 3) Prescribed by or in consultation with a nephrologist; 4) Age >= 12 years; 5) Urine protein‑to‑creatinine ratio (UPCR) >= 1 g/g; 6) Estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m^2; 7) Failure of at least a 12‑week trial of a RAAS inhibitor (ACEI or ARB) at up to maximally indicated doses unless contraindicated or not tolerated; 8) Empaveli is not prescribed concurrently with Syfovre or another FDA‑approved product for C3G/IC‑MPGN (e.g., Fabhalta) outside of any allowed switching window; 9) Dose per weight‑based regimen (adults and pediatric >=50 kg: 1,080 mg SC twice weekly; 35 to <50 kg: 810 mg SC twice weekly; <35 kg: 648 mg SC twice weekly) and does not exceed labeled maximums

Approval duration: typically 12 months

Initial Approval — Geographic Atrophy (GA) secondary to AMD

Covered when ALL of the following are met:

GA initial criteria: 1) Diagnosis of geographic atrophy (GA) secondary to age‑related macular degeneration (AMD); 2) GA characteristics confirmed on fundus autofluorescence imaging including: total GA area >= 2.5 and < 17.5 mm^2 (1 to 7 disk areas), lesions not contiguous with peripapillary atrophy, if multifocal at least one lesion >= 1.25 mm^2, and presence of hyperautofluorescence in the junctional zone; 3) Best corrected visual acuity (BCVA) of >= 24 ETDRS letters (approximately 20/320 Snellen equivalent); 4) Prescribed by or in consultation with an ophthalmologist; 5) Request is for Syfovre (intravitreal pegcetacoplan); 6) No history of or active choroidal neovascularization (CNV) in the affected eye(s); 7) Syfovre is not prescribed concurrently with Empaveli; 8) Dose does not exceed 15 mg (0.1 mL of 150 mg/mL solution) per affected eye every 25 days

Approval duration: 12 months; diagnostic confirmation must be on fundus autofluorescence imaging per plan request and pivotal study alignment.

Continued Therapy — General

Covered when ALL of the following general conditions are met for continuation:

Continued therapy general: 1) Member is currently receiving the medication via the Centene benefit or has previously met initial approval criteria; 2) Request is for the same product initially approved (Empaveli for PNH or C3G/IC‑MPGN; Syfovre for GA); 3) Member is responding positively to therapy as evidenced by indication‑specific clinical improvement (examples: for PNH — improved intravascular/extravascular hemolysis measures such as normalization or reduction in LDH, reduced reticulocyte count, increased or stabilized hemoglobin, reduced transfusion need, improved symptoms; for C3G/IC‑MPGN — reduction in proteinuria/UPCR; for GA — clinical evidence of therapeutic response per ophthalmology assessment); 4) Empaveli/Syfovre are not prescribed concurrently with disallowed complement‑targeted agents outside of allowed cross‑titration or switching windows; 5) Dose increases must not exceed indication‑specific maximums (PNH: <= 2,160 mg/week or 1,080 mg every 3 days; GA: <= 15 mg/eye every 25 days) and LDH or other monitoring thresholds are met when applicable

Approval duration typically 12 months for continued therapy; provider must submit supporting documentation (office notes, labs, imaging).

PNH (Empaveli) coverage criteria

Coverage applies when dosing, indication, and restrictions per product labeling and health plan criteria are met.

PNH systemic therapy (Empaveli): Patient indication consistent with PNH and dosing per label: adults >=50 kg — 1,080 mg SC twice weekly; weight‑based pediatric dosing as specified (>=50 kg: 1,080 mg twice weekly; 35 to <50 kg: 810 mg twice weekly; <35 kg: 648 mg twice weekly). For patients switching from Soliris/Bkemv/Epysqli, initiate Empaveli while continuing prior therapy and discontinue the prior complement inhibitor after 4 weeks; for switches from Ultomiris, initiate Empaveli within 4 weeks of the last Ultomiris dose. Adjust dosing for LDH >= 2x ULN. Empaveli should not be prescribed concurrently with listed complement‑targeted therapies (e.g., Soliris, Ultomiris, Fabhalta, Voydeya, Bkemv, Epysqli, PiaSky) outside allowed cross‑titration or switching windows. Maximum Empaveli dosing limits apply and must be documented in the request.

Continued approval duration for chronic PNH revised to 12 months; provider must document dosing regimen and any cross‑titration/switching details.

Geographic Atrophy coverage criteria

Coverage applies for GA secondary to AMD when diagnostic and dosing requirements are met per label and plan imaging confirmation.

GA (Syfovre/APL-2): Indication for geographic atrophy secondary to AMD with diagnostic confirmation on fundus autofluorescence imaging per plan request (total GA area >= 2.5 and < 17.5 mm^2; lesions not contiguous with peripapillary atrophy; if multifocal at least one lesion >= 1.25 mm^2; presence of hyperautofluorescence in the junctional zone). Dose and administration per label: 15 mg (0.1 mL of 150 mg/mL) intravitreal injection to each affected eye with maximum frequency every 25 days. Exclude eyes with active or history of CNV only in the affected eye(s). HCPCS code J2781 applies for intravitreal pegcetacoplan dosing/billing as available. Contraindications and hypersensitivity per updated prescribing information apply.

Approval duration: 12 months; fundus autofluorescence imaging confirmation required per health plan request.

Non‑FDA approved indications that are not specifically addressed in this policy are not covered unless the provider supplies sufficient supporting documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 for commercial, HIM.PA.154 for the health insurance marketplace, and CP.PMN.53 for Medicaid.

Empaveli (pegcetacoplan systemic formulation) must not be prescribed concurrently with other complement‑targeted therapies except within specified cross‑titration or switching windows. The policy explicitly lists restricted agents for PNH, including Fabhalta, Voydeya, Bkemv, Soliris, and Ultomiris, and was recently updated to also include Epgetsi/Epigslist-type agents (Epigslist/Epiginna/Epighinn/Epysqli) and PiaSky (added 3Q 2025). An exception is provided for defined cross‑titration periods (for example, a 4‑week overlap when initiating Empaveli while discontinuing certain C5 inhibitors); providers must document timing of prior and planned doses when requesting authorization.

Uses that are not listed in the covered diagnoses/indications sections of this policy, or uses subject to the plan’s no‑coverage/non‑formulary/off‑label policies, are not authorized. Refer to the applicable line‑of‑business policies for guidance: commercial — CP.CPA.190 (no‑coverage) or CP.CPA.09 (off‑label); health insurance marketplace — HIM.PA.33 (no‑coverage) or HIM.PA.154 (off‑label); Medicaid — CP.PMN.255 (no‑coverage) or CP.PMN.53 (off‑label).

Policy history notes that the prior requirement for at least one RBC transfusion in the 12 months before Empaveli initiation was removed after review of trial data (PEGASUS), which showed a substantial proportion of patients with no prior transfusions and no difference in treatment effect; therefore, documentation of a recent RBC transfusion is not required for initial approval.

Coding, Dosing Limits, and Clinical Thresholds

HCPCS Codes referencedHCPCS

J2781	Injection, pegcetacoplan, intravitreal, L mg
J7799	Not otherwise classified drugs, other than inhalation, administered through DME drugs
C9151	Inactive HCPCS code (removed)

Total GA area — lesion size threshold for GA eligibility

Total GA area>= 2.5 and < 17.5 mm^2 (1 to 7 disk areas)

Lesion contiguityGA lesions must not be contiguous with peripapillary atrophy

Multifocal lesion sizeIf multifocal, at least one focal lesion >= 1.25 mm^2 (0.5 DA)

Empaveli dosing limit (PNH) — weekly and per-dose maxima

Weekly maximum (PNH)Does not exceed 2,160 mg per week

Per-dose maximumMaximum 1,080 mg per dose (also specified as 1,080 mg every 3 days)

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Empaveli and Syfovre. Submit a prior authorization request with all required clinical documentation demonstrating the member meets the diagnosis-specific criteria in this policy. Requests without sufficient documentation may be denied.

Include appropriate HCPCS/CPT/ICD-10 codes on the request — e.g., J2781 for subcutaneous pegcetacoplan administration when applicable and product‑specific HCPCS for intravitreal pegcetacoplan (Syfovre).
For intravitreal pegcetacoplan (Syfovre) include the eye-level diagnosis and laterality.
For Empaveli, include indication-specific coding (PNH vs C3G/IC‑MPGN) and any relevant procedure/administration codes.

Documentation Required

Provide supporting clinical documentation with the prior authorization request. Acceptable documentation includes office visit notes, consultation notes, specialty clinic notes, hospital records, procedure notes, laboratory results (e.g., LDH, hemoglobin, eGFR, UPCR), imaging reports (e.g., fundus autofluorescence for GA), and pathology reports (e.g., kidney biopsy).

Background and Drug Overview

Pegcetacoplan is a targeted complement inhibitor that binds to C3 and C3b, reducing complement‑mediated activity. It is available as a systemic subcutaneous formulation (Empaveli) approved for paroxysmal nocturnal hemoglobinuria (PNH) and certain glomerular complement disorders (C3 glomerulopathy and primary immune‑complex membranoproliferative glomerulonephritis), and as an intravitreal formulation (Syfovre/APL‑2) approved for geographic atrophy (GA) secondary to age‑related macular degeneration. Dosing and administration differ by formulation and indication (for example, Empaveli systemic dosing for adults typically uses 1,080 mg SC twice weekly, while Syfovre intravitreal dosing is 15 mg per affected eye every 25 days); refer to the dosing sections and product labeling for full instructions.

Definitions and Abbreviations

GPI — define glycosylphosphatidylinositol as used in flow cytometry criteria

Definition (GPI)GPI = glycosylphosphatidylinositol; abbreviation used in flow cytometry criteria to identify GPI-deficient hematopoietic clones

ContextFlow cytometry demonstrating detectable GPI-deficient clones (>= 10% PNH cells) is required for PNH eligibility

Appendix referenceListed in Appendix A: Abbreviation/Acronym Key

LDH — define lactate dehydrogenase (marker and thresholds referenced)

Definition (LDH)LDH = lactate dehydrogenase; a marker of hemolysis referenced for threshold-based dosing decisions

Thresholds referencedPolicy references LDH > 2x ULN as condition for dose adjustment or documentation when dosing at upper limit

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Clinical Policy: Pegcetacoplan (Empaveli, Syfovre) — Coverage Criteria

Coverage Criteria for Pegcetacoplan (Empaveli, Syfovre)

Coding, Dosing Limits, and Clinical Thresholds

Provider Requirements, Prior Authorization, and Documentation

Background and Drug Overview

Definitions and Abbreviations