Pegcetacoplan (Empaveli) — Coverage Criteria for Subcutaneous Infusion
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Medical necessity and site-of-care criteria for pegcetacoplan (Empaveli) subcutaneous infusion for treatment of PNH, C3G, and IC-MPGN for Blue Cross NC members.
For PNH indication, diagnostic criteria now require flow cytometry and LDH ≥ 1.5× ULN at baseline prior to starting complement inhibitor therapy.
Age requirement of 12 years or older was added for C3G and IC-MPGN indications according to FDA label.
Requirement for reduced serum C3 for the C3G indication was removed.
Site of care criteria expanded to allow outpatient hospital administration for patients with prior severe adverse events or conditions increasing risk for severe adverse events.
Medical Necessity: Coverage Criteria
Initial therapy — PNH
Covered when ALL of the following are met for PNH
Includes documented transition allowance from eculizumab with planned discontinuation 4 weeks after pegcetacoplan initiation
Initial therapy — C3G
Covered when ALL of the following are met for C3G
Medical record documentation required for each element; duration of initial approval = 90 days
Initial therapy — IC-MPGN
Covered when ALL of the following are met for IC-MPGN
Medical record documentation required for each element; duration of initial approval = 90 days
Provider, quantity, and site-of-care conditions
Additional approval conditions
Duration of initial approval = 90 days; continuation requests must be submitted via the member's pharmacy benefit prior authorization process per Blue Cross NC guidance
Use of pegcetacoplan in combination with another complement inhibitor for the same indication is prohibited. An exception is allowed only for a documented transition from an eculizumab product to pegcetacoplan when medical records show the patient is switching therapies and the eculizumab product will be discontinued 4 weeks after initiation of pegcetacoplan.
Requests lacking required diagnostic confirmation, baseline laboratory values, age criteria, evidence of prior therapy optimization, measured renal function, or appropriate specialist involvement are not medically necessary. Examples include missing flow cytometry confirmation for PNH or absence of documentation that baseline LDH ≥ 1.5× ULN was present prior to starting therapy; for C3G/IC-MPGN, missing documentation of age ≥ 12 years, UPCR ≥ 0.88 g/g (or proteinuria > 1.0 g/day), failure or optimization on a maximally tolerated RAS inhibitor for ≥ 90 days (or documented intolerance/contraindication), or measured GFR ≥ 30 mL/min/1.73 m2. Also required is documentation that the prescriber is an appropriate specialist or that a specialist consultation occurred.
Billing and Key Clinical Thresholds
Provider Responsibilities and Prior Authorization
Prior authorization required; bill using C9399, J3490, J3590
Prior authorization is required for pegcetacoplan (Empaveli) subcutaneous infusion. Use the following HCPCS/billing codes for SC administration: C9399, J3490, J3590. The policy table lists maximum units (27,000) for dosing/quantity limits.
Document ≥90 days of maximally tolerated RAS inhibitor or intolerance
For C3G and IC‑MPGN, the patient must be currently treated with a maximally tolerated renin‑angiotensin system (RAS) inhibitor (ACEi or ARB) for at least 90 days, or have documented clinical intolerance/contraindication to ACEi/ARB therapy.
- Document duration of RAS inhibitor therapy (≥90 days) or documentation of intolerance/contraindication to ACEi/ARB.
Provide required diagnostic and baseline laboratory documentation
Include medical record documentation verifying diagnostic and baseline laboratory criteria: flow cytometry confirmation for PNH; baseline LDH for PNH; and UPCR and measured GFR for C3G/IC‑MPGN. Also document age, specialist prescriber/consult, prior therapies, and that the agent will not be used concomitantly with another complement inhibitor.
- PNH: flow cytometry with ≥2 independent reagents on ≥2 cell lineages demonstrating GPI‑AP deficiency; baseline LDH ≥ 1.5× ULN.
- C3G/IC‑MPGN: UPCR ≥ 0.88 g/g or proteinuria > 1.0 g/day, and measured GFR ≥ 30 mL/min/1.73 m2.
- Document age eligibility, specialist prescriber or consult, prior therapy history (e.g., RAS inhibitor use or intolerance), and no concurrent complement inhibitor use (or planned eculizumab discontinuation if transitioning).
Incomplete documentation (flow cytometry, LDH, UPCR/GFR) may result in denial
Requests lacking the required medical record documentation may be denied — specifically missing flow cytometry for PNH, missing baseline LDH ≥ 1.5×ULN, or missing UPCR/GFR documentation for C3G/IC‑MPGN, and absence of specialist prescriber/consult documentation.
- Missing PNH confirmation by flow cytometry may lead to denial.
- Absence of baseline LDH meeting ≥1.5× ULN may lead to denial.
- Lack of UPCR and/or GFR documentation for C3G/IC‑MPGN may lead to denial.
- Requests without specialist prescriber or consult documentation may be denied.
Background and Drug Summary
Pegcetacoplan is a complement C3 inhibitor with labeled indications for paroxysmal nocturnal hemoglobinuria (PNH) in adults and, per updated labeling, for treatment of complement 3 glomerulopathy (C3G) and primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) in patients aged ≥ 12 years to reduce proteinuria. For PNH, diagnosis confirmation requires flow cytometry with ≥2 independent reagents on ≥2 cell lineages demonstrating GPI-anchored protein deficiency and evidence of hemolysis with baseline LDH ≥ 1.5× ULN prior to starting complement inhibitor therapy. Management of C3G and IC-MPGN in this policy expects documentation of proteinuria thresholds (UPCR ≥ 0.88 g/g or proteinuria > 1.0 g/day), renal function (GFR ≥ 30 mL/min/1.73 m2), and prior optimization of RAS blockade before initiating complement-targeted therapy.
Key Diagnostic Definitions and Thresholds
Initial Dosing and Administration
Initial dosing — Dosing per FDA label reference
Dosing per FDA label reference
Applies to PNH and most adult C3G/IC-MPGN dosing per FDA label reference
Per FDA label reference table
Criteria for Continued Therapy
Continuation therapy routing — Continuation of therapy criteria and monitoring
Continuation of therapy
Duration of initial approval = 90 days
Step Therapy Requirements
| Step | Requirement | Documentation Required |
|---|---|---|
| 1 | ||
| Patient must be currently treated with a maximally tolerated renin-angiotensin system (RAS) inhibitor (e.g., ACEi or ARB) for at least 90 days OR have documented clinical intolerance/contraindication to ACEi and ARB therapy | ||
| Medical record documentation of RAS inhibitor therapy for ≥90 days OR documentation of intolerance/contraindication to ACEi/ARB |
Quantity Limits and Maximum Units
Permitted Sites of Administration
Follow site‑of‑care rules; inpatient allowed only if admission not solely for infusion; outpatient hospital allowed with qualifying risk/history
Inpatient administration is allowed if the admission is not solely for infusion; outpatient hospital administration is allowed when medical necessity criteria are met and one of the listed risk/history conditions applies (e.g., prior severe adverse event, conditions increasing risk, inability to adhere, new or re‑initiation of therapy). If site‑of‑care criteria are not met, administration is expected in home or physician office settings.
- Inpatient: permitted only when admission is not solely for infusion and medical necessity criteria are met.
- Outpatient hospital: permitted if medical necessity criteria are met AND one qualifying condition (severe prior adverse event, increased risk conditions, uncontrolled mild adverse events, inability to adhere, new to therapy, re‑initiation, or formulation change) is present.
- If neither inpatient nor outpatient hospital criteria are met, administer in home or physician office.
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