Pegcetacoplan (Empaveli) Form

Pegcetacoplan (Empaveli™, Syfovre™) is a C3/C3b complement inhibitor. FDA Approved Indication(s)
Empaveli is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH). Syfovre is indicated for the treatment of adult patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Empaveli and Syfovre are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Paroxysmal Nocturnal Hemoglobinuria (must meet all):

1. Diagnosis of PNH;
   2. Request is for Empaveli;
   3. Prescribed by or in consultation with a hematologist;
   4. Age ≥ 18 years;
   5. Flow cytometry shows detectable glycosylphosphatidylinositol (GPI)-deficient hematopoietic clones or ≥ 10% PNH cells;
   6. Documentation of hemoglobin < 10.5 g/dL;
   7. Empaveli is not prescribed concurrently with either of the following (a and b): a. Syfovre; b. Another FDA-approved product for PNH (e.g., Soliris®, Ultomiris®), unless the member is in a 4-week period of cross-titration between Soliris and Empaveli;Provider must submit attestation of the presence or absence of concomitant Soliris therapy

2. Dose does not exceed 2,160 mg per week or 1,080 mg every 3 days (total 10 doses per month) with documentation of a lactate dehydrogenase (LDH) level greater than 2 times the upper limit of normal (ULN). Approval duration: 6 weeks (if within cross-titration period with Soliris), or 6 months Page 1 of 8

   CLINICAL POLICY Pegcetacoplan B. Geographic Atrophy (must meet all):

3. Diagnosis of GA with all of the following characteristics (a, b, c, d, and e): a. GA is secondary to AMD; b. Total GA area ≥ 2.5 and ≤ 17.5 mm2 (1 and 7 disk areas [DA] respectively); c. If GA is multifocal, at least one focal lesion ≥ 1.25 mm2 (0.5 DA); d. GA lesion(s) are not contiguous with any areas of peripapillary atrophy; e. Presence of hyperautofluorescence in the junctional zone of GA;
4. Request is for Syfovre;
   3. Prescribed by or in consultation with an ophthalmologist;
   4. Age ≥ 60 years;
   5. Best corrected visual acuity (BCVA) of 24 letters or better on Early Treatment Diabetic Retinopathy Study (ETDRS) charts (approximately 20/320 Snellen equivalent);
5. Member does not have either of the following (a and b): a. Diagnosis of any condition that may cause GA, including but not limited to pathologic myopia, Stargardt disease, cone rod dystrophy, and toxic maculopathies like Plaquenil maculopathy; b. History of or active choroidal neovascularization (CNV) in the eye(s) affected by GA;
6. Syfovre is not prescribed concurrently with Empaveli;
   8. Dose does not exceed 15 mg (0.1 mL of 150 mg/mL solution) in each affected eye every 25 days. Approval duration: 12 months C. Other diagnoses/indications (must meet 1 or 2):
7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Paroxysmal Nocturnal Hemoglobinuria (must meet all):

9. Member meets one of the following (a or b): Page 2 of 8

   CLINICAL POLICY Pegcetacoplan a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

10. Request is for Empaveli;
    3. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters (a – f): a. Improved measures of intravascular hemolysis (e.g., normalization of lactate dehydrogenase); b. Reduced need for red blood cell transfusions; c. Increased or stabilization of hemoglobin levels; d. Less fatigue; e. Improved health-related quality of life; f. Fewer thrombotic events;
11. Empaveli is not prescribed concurrently with either of the following (a and b): a. Syfovre; b. Another FDA-approved product for PNH (e.g., Soliris, Ultomiris);
12. If request is for a dose increase, new dose does not exceed 2,160 mg per week or 1,080 mg every 3 days (total 10 doses per month) with documentation of an LDH level greater than 2 times the ULN. Approval duration: 6 months B. Geographic Atrophy (must meet all):
13. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
14. Request is for Syfovre;
    3. Member is responding positively to therapy;
    4. Syfovre is not prescribed concurrently with Empaveli;
    5. If request is for a dose increase, new dose does not exceed 15 mg (0.1 mL of 150 mg/mL solution) in each affected eye every 25 days. Approval duration: 12 months C. Other diagnoses/indications (must meet 1 or 2):

15. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or Page 3 of 8

    CLINICAL POLICY Pegcetacoplan b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

16. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AMD: age-related macular degeneration BCVA: best corrected visual acuity CNV: choroidal neovascularization DA: disk area ETDRS: Early Treatment Diabetic Retinopathy Study GA: geographic atrophy GPI: glycosylphosphatidylinositol LDH: lactate dehydrogenase PNH: paroxysmal nocturnal hemoglobinuria REMS: Risk Evaluation and Mitigation Strategy FDA: Food and Drug Administration ULN: upper limit of normal Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings
    • Contraindication(s):
    o Empaveli: hypersensitivity to pegcetacoplan or any of the excipients; patients who are not currently vaccinated against certain encapsulated bacteria unless the risks of delaying Empaveli treatment outweigh the risks of developing a serious bacterial infection with an encapsulated organism; patients with unresolved serious infection caused by encapsulated bacteria o Syfovre: ocular or periocular infections; active intraocular inflammation • Boxed warning(s):
    o Empaveli: serious infections caused by encapsulated bacteria; Empaveli is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) o Syfovre: none reported Page 4 of 8

    CLINICAL POLICY Pegcetacoplan V. Dosage and Administration
    Drug Name Empaveli Indication Dosing Regimen PNH 1,080 mg by SC infusion twice weekly via a commercially available pump Maximum Dose 1,080 mg/dose For patients switching from Soliris, initiate Empaveli while continuing Soliris at its current dose. After 4 weeks, discontinue Soliris before continuing on monotherapy with Empaveli. For patients switching from Ultomiris, initiate Empaveli no more than 4 weeks after the last dose of Ultomiris. For LDH levels > 2x ULN, adjust the dosing regimen to 1,080 mg every three days. 15 mg (0.1 mL of 150 mg/mL solution) via intravitreal injection to each affected eye once every 25 to 60 days 15 mg/25 days Syfovre GA VI. Product Availability
    Drug Name Empaveli Syfovre Availability Single-dose vial for subcutaneous injection: 1,080 mg/20 mL Single-dose vial for intravitreal injection: 150 mg/mL VII.