Centene pegcetacoplan coverage update

Coverage Criteria

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 subcutaneous). 3. Prescribed by or in consultation with a hematologist. 4. Age ≥ 18 years. 5. Flow cytometry demonstrating detectable GPI-deficient hematopoietic clones or ≥ 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, Epijkstra, PiaSky), unless the member is in a 4‑week cross‑titration period between Soliris/Bkemv/Epijkstra and Empaveli; provider must submit attestation regarding concomitant Soliris/Bkemv/Epijkstra therapy. 8. Dose does not exceed 2,160 mg per week or 1,080 mg every 3 days (total 10 doses per month) except when documented LDH > 2 x ULN justifies adjusted dosing per label.see nodes

Approval duration: 6 weeks if within cross‑titration period with Soliris; otherwise 6 months.

Initial Approval — C3 Glomerulopathy 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 (IC‑MPGN) confirmed by kidney biopsy (not recurrent disease post‑transplant for IC‑MPGN). 2. Request is for Empaveli. 3. Prescribed by or in consultation with a nephrologist. 4. Age ≥ 12 years. 5. Documentation of both: a) urine protein‑to‑creatinine ratio (UPCR) ≥ 1 g/g; and b) eGFR ≥ 30 mL/min/1.73 m2. 6. Failure of at least a 12‑week trial of a RAAS inhibitor at up to maximally indicated doses unless contraindicated or intolerant. 7. Empaveli is not prescribed concurrently with Syfovre or another FDA‑approved product for C3G/IC‑MPGN (e.g., Fabhalta). 8. Dose does not exceed weight‑based regimens: adults and pediatric members ≥50 kg: 1,080 mg twice weekly; 35 to <50 kg: 810 mg twice weekly; <35 kg: 648 mg twice weekly.see nodes

For Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

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: a) total GA area ≥ 2.5 and ≤ 17.5 mm2; b) if multifocal, at least one lesion ≥ 1.25 mm2; c) lesion(s) not contiguous with peripapillary atrophy; d) presence of hyperautofluorescence in the junctional zone. 3. Request is for Syfovre (intravitreal pegcetacoplan). 4. Prescribed by or in consultation with an ophthalmologist. 5. Age ≥ 60 years. 6. Best corrected visual acuity (BCVA) of ≥ 24 ETDRS letters (≈20/320). 7. No other condition that may cause GA and no history of or active choroidal neovascularization in the affected eye(s). 8. Syfovre is not prescribed concurrently with Empaveli. 9. Dose does not exceed 15 mg (0.1 mL of 150 mg/mL) in each affected eye every 25 days.see nodes

Approval duration: 12 months.

Continuation/Renewal Criteria by Indication

Covered when ALL of the following are met (by indication)

PNH Continuation: 1. Member is currently receiving Empaveli via Centene benefit or has previously met initial approval criteria. 2. Request is for Empaveli. 3. Member is responding positively to therapy (examples include improved hemolysis markers, reduced transfusion requirements, stabilized or increased hemoglobin, reduced fatigue, improved quality of life, or fewer thrombotic events). 4. Empaveli is not prescribed concurrently with Syfovre or another FDA‑approved PNH product. 5. If a dose increase is requested, new dose does not exceed 2,160 mg/week or 1,080 mg every 3 days (total 10 doses/month) unless justified by documented LDH > 2 x ULN.see nodes

Approval duration: 12 months.

C3G/IC‑MPGN Continuation: 1. Member is currently receiving Empaveli via Centene benefit or has previously met initial approval criteria. 2. Request is for Empaveli. 3. Member is responding positively as evidenced by decreased UPCR or reduced total urine protein/day from baseline. 4. Empaveli is not prescribed concurrently with Syfovre or another FDA‑approved product for C3G/IC‑MPGN. 5. If a dose increase is requested, new dose does not exceed the weight‑based regimens noted for initial therapy.see nodes

Approval duration: 12 months.

Other/Off-Label Uses

Covered only when specified conditions met

Other/Off‑Label Uses: 1. If the drug has had a label change within the last 6 months that is not yet reflected in this policy (e.g., newly approved indication, age expansion, new dosing), follow the referenced formulary/no‑coverage/non‑formulary policies for the applicable line of business (see policy cross‑references). OR 2. If the requested use is not specifically listed under 'Diagnoses/Indications for which coverage is NOT authorized' and criterion 1 does not apply, the request should be evaluated per the off‑label use policy for the relevant line of business.see nodes

See cross‑references: CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16, CP.CPA.09, HIM.PA.154, CP.PMN.53.

Covered Indications and Dosing

Covered when meeting indication-specific dosing and administration guidance per FDA labeling and policy updates

Transitioning from other complement inhibitors: For patients switching from Soliris, Bkemv, or Epijkstra, initiate Empaveli while continuing the prior agent at its current dose and discontinue the prior agent after 4 weeks before continuing Empaveli monotherapy. When switching from Ultomiris, initiate Empaveli within 4 weeks after the last Ultomiris dose.within 4 weeks

Policy restricts concurrent use with listed therapies except per allowed transition timing; updates have added additional restricted agents.

Empaveli dosing for PNH: 1,080 mg subcutaneously twice weekly (maximum 1,080 mg per dose); adjust dosing per product information when LDH > 2 x ULN.LDH > 2 x ULN

Maximum dose and LDH‑based adjustments per prescribing information.

Empaveli dosing for C3G/IC‑MPGN: Empaveli dosing for C3G/primary IC‑MPGN (weight‑based): adults and pediatric members ≥50 kg: 1,080 mg SC twice weekly; 35 to <50 kg: 810 mg SC twice weekly; <35 kg: 648 mg SC twice weekly.

Non-FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider submits sufficient supporting documentation in accordance with the applicable off‑label use policies. See CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid) for the required evidence of efficacy and safety and any additional documentation requirements.

Empaveli should not be prescribed concurrently with the listed complement‑targeting therapies outside of allowed transition periods; the policy was updated to add therapies (e.g., Fabhalta, Voydeya, Bkemv, Epysqli, PiaSky and others) to the restricted list. When transitioning from certain complement inhibitors, the policy permits brief, documented overlap (for example, continuing the prior agent for 4 weeks after initiating Empaveli when switching from Soliris/Bkemv/Epysqli, or initiating Empaveli within 4 weeks after the last Ultomiris dose). Providers must document the rationale and timing of any cross‑titration or overlap.

Uses of pegcetacoplan for non‑FDA approved indications that lack adequate evidence or an approved off‑label justification are considered not authorized under this policy. Requests for such uses must follow the referenced off‑label use policies and include documentation demonstrating efficacy and safety to be considered for coverage.

Billing and coding entries included in this clinical policy are provided for informational purposes only. Inclusion of codes does not guarantee coverage; providers must verify current professional coding guidance and applicable payer billing requirements prior to claims submission.

Initial Therapy Criteria

Initial Therapy — Initial authorization requires meeting indication-specific diagnostic, prescriber specialty, age, and measurable clinical thresholds

Initial authorization requires meeting indication-specific diagnostic, prescriber specialty, age, and measurable clinical thresholds

Diagnostic confirmation: Requests must include documentation confirming the diagnosis per indication: PNH (flow cytometry with GPI‑deficient clones or ≥10% PNH cells), C3G/IC‑MPGN (kidney biopsy confirmation), or GA (fundus autofluorescence imaging meeting specified lesion size and characteristics).

Attach relevant diagnostic reports/imaging and laboratory results.

Prescriber specialty and age: Prescription must be written by or in consultation with the specialty appropriate to the indication: hematologist for PNH, nephrologist for C3G/IC‑MPGN, ophthalmologist for GA. Age thresholds: PNH ≥18 years; C3G/IC‑MPGN ≥12 years; GA ≥60 years.

Provide documentation of specialist consultation when applicable.

Measurable clinical thresholds:

Continuation / Renewal Criteria

Continuation Therapy — Continuation criteria mirror initial criteria and require evidence of clinical response and absence of concurrent disallowed therapies

Continuation criteria mirror initial criteria and require evidence of clinical response and absence of concurrent disallowed therapies

General continuation requirements: 1. Member is currently receiving the requested pegcetacoplan product via Centene benefit or previously met initial approval criteria. 2. Request is for continuation of the same product. 3. Member demonstrates clinical response to therapy appropriate to the indication. 4. Therapy is not being used concurrently with a disallowed complement‑targeting product for the same indication. 5. Dose requests continue to meet the dosing limits established for the indication.

Approval duration generally: 12 months.

Continued Therapy — Continued approval and response criteria for chronic PNH therapy

Continued approval and response criteria for chronic PNH therapy

PNH continued therapy: Continued approval duration for chronic PNH therapy has been revised to 12 months. Evidence of positive response may include improvement in extravascular hemolysis parameters, reduced transfusion needs, stabilized or increased hemoglobin, normalized or improved hemolysis markers, and fewer thrombotic events.

Provider Action & Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization required — Prior authorization is required for Empaveli and Syfovre. Requests must include clinical documentation demonstrating the specific indication criteria are met.

Prior authorization required for Empaveli and Syfovre
Submit clinical documentation demonstrating member meets all indication-specific criteria

Billing Rule

HCPCS Codes and Prior Authorization

HCPCS coding and prior authorization — Certain pegcetacoplan products may be billed under HCPCS and require prior authorization when billed as such. Verify and include the appropriate HCPCS code(s) on the PA request and claims.

HCPCS J2781 = Injection, pegcetacoplan, intravitreal, 1 mg (example for intravitreal pegcetacoplan/Syfovre)

Coding and Billing

GA total area — GA lesion area thresholds

GA total area>= 2.5 and <= 17.5 mm^2

Multifocal lesion minimum sizeIf multifocal, at least one lesion >= 1.25 mm^2

Contiguity requirementLesions must not be contiguous with areas of peripapillary atrophy

PNH hemoglobin threshold — Hemoglobin threshold for PNH eligibility

Hemoglobin threshold for PNH eligibility< 10.5 g/dL

Supporting criterionDocumentation of hemoglobin < 10.5 g/dL required for initial PNH approval

Continuation note

Step Therapy & Prior Trials

Step	Requirement
RAAS inhibitor trial	Documentation of failure of at least a 12-week trial of a renin-angiotensin-aldosterone system (RAAS) inhibitor (e.g., irbesartan, losartan, lisinopril, benazepril) at up to maximally indicated doses is required prior to initiation of Empaveli for C3G or primary IC‑MPGN unless contraindicated or clinically significant adverse effects are experienced.

Restriction	Policy detail / allowed overlap
Concurrent complement‑targeting therapies	Empaveli should not be prescribed concurrently with listed complement‑targeting therapies (examples include Fabhalta, Voydeya, Bkemv, Epysqli, PiaSky, Soliris, Ultomiris, and other FDA‑approved products for the same indications).
Allowed short overlap for transitions	When switching from Soliris, Bkemv, or Epysqli, initiate Empaveli while continuing the prior agent at its current dose and discontinue the prior agent after 4 weeks (4‑week cross‑titration). When switching from Ultomiris, initiate Empaveli no more than 4 weeks after the last Ultomiris dose. Such brief overlap for transition must be documented with timing and rationale.

Quantity Limits & Dosing

Empaveli — 1,080 mg per dose (standard adult dose)

Standard adult Empaveli dose1,080 mg per dose (subcutaneous)

Product presentationEmpaveli supplied as single-dose vial for subcutaneous injection: 1,080 mg/20 mL

Typical regimen for PNH1,080 mg SC twice weekly for PNH (per dosing regimen)

Empaveli (PNH) — <= 2,160 mg per week or 1,080 mg every 3 days (max 10 doses/month for certain dosing with LDH>2xULN)

Weekly and per-dose limits for PNH<= 2,160 mg per week or 1,080 mg every 3 days

Maximum dosing allowance with LDH elevationTotal of 10 doses per month allowed when dosing increase is supported by LDH > 2x ULN

Site of Care & Administration

Note

Product presentations and administration settings (vials and routes)

Empaveli is supplied as single‑dose vials for subcutaneous injection; Syfovre is supplied as single‑dose vials for intravitreal injection and dosing/administration differs by setting and presentation.

Empaveli vial: 1,080 mg/20 mL for SC administration.
Syfovre vial: 150 mg/mL intravitreal formulation (0.1 mL = 15 mg).

Note

Office administration specifics for Empaveli (SC) and Syfovre (intravitreal)

Empaveli is administered subcutaneously (including by the on‑body injector per label); Syfovre is administered via intravitreal injection in the ophthalmology/office setting.

Syfovre intravitreal injections are performed in an ophthalmology office setting.
Empaveli SC dosing and administration instructions, including on‑body injector use, are per the product label.

Background

Pegcetacoplan is a complement C3/C3b inhibitor available in systemic and intravitreal formulations. The systemic formulation, Empaveli, is supplied as a single‑dose vial for subcutaneous administration and is indicated for conditions such as paroxysmal nocturnal hemoglobinuria and, per recent FDA updates, C3 glomerulopathy/primary IC‑MPGN; dosing varies by indication and weight. The intravitreal formulation, Syfovre, is administered as a 15 mg intravitreal injection per affected eye with labeling supporting dosing intervals down to every 25 days. Product availability and contraindication updates were incorporated into the policy during the 3Q 2024 and 3Q 2025 reviews.

Definitions

GA — Geographic atrophy definition

Definition of Geographic Atrophy (GA)GA secondary to age-related macular degeneration confirmed by fundus autofluorescence imaging

Imaging criteria summaryTotal GA area and lesion characteristics (see lesion size, multifocal lesion criteria, junctional zone hyperautofluorescence)

Exclusion examplesGA must not be due to other causes like Stargardt disease, pathologic myopia, cone rod dystrophy, or toxic maculopathies

PNH — Paroxysmal nocturnal hemoglobinuria definition

Definition of PNHParoxysmal nocturnal hemoglobinuria (PNH) — diagnosis supported by flow cytometry showing GPI-deficient clones or >= 10% PNH cells

Diagnostic testingFlow cytometry demonstrating detectable GPI-deficient hematopoietic clones or >= 10% PNH cells required

OpenPayer

Pegcetacoplan (Empaveli, Syfovre) coverage

Coverage Criteria

Initial Therapy Criteria

Continuation / Renewal Criteria

Provider Action & Documentation Requirements

Coding and Billing

Step Therapy & Prior Trials

Quantity Limits & Dosing

Site of Care & Administration

Background

Definitions