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Empaveli (pegcetacoplan) Prior Authorization with Quantity Limit Program Summary
Policy Number: PH-1154
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
7/1/2023 |
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FDA APPROVED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Empaveli™ (pegcetacoplan) Injection for subcutaneous use |
Treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)
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1 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Paroxysmal Nocturnal Hemoglobinuria |
Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, life-threatening, rare, multi-systemic disease developing as a result of somatic mutation of hematopoietic stem cells, and characterized by clonal, complement-mediated intravascular hemolysis. PNH is mainly a disease of adults with a median age of onset in the thirties. High Precision Flow Cytometry is the most useful and accepted diagnostic test to confirm the diagnosis of PNH. Flow cytometry is performed by incubating the patient’s peripheral blood cells with fluorescently-labeled monoclonal antibodies that bind to glycosylphosphatidylinositol (GPI) anchored proteins, which are reduced or absent on blood cells in PNH. Since different blood cell lineages display different combinations of GPI-linked proteins, and some proteins bind to cell surfaces via both GPI-linked and GPI-independent mechanisms, it is recommended that at least two independent flow cytometry reagents be used on at least two cell lineages (e.g., RBCs and WBCs) to establish the diagnosis of PNH.(2)
Lack of the complement inhibitor CD59 the red blood cells surface is mostly responsible for the clinical manifestations in PNH. These patients manifest with chronic intravascular hemolysis, paroxysmal flares of hemolysis and a propensity for thrombosis. Intravascular hemolysis leads to release of free hemoglobin (Hb) into the blood. Free hemoglobin, in turn, can cause various toxic effects, including hypercoagulability, changes in vascular tone from reduction of circulating nitric oxide and renal damage.(3)
Extravascular hemolysis also occurs in patients with PNH because C3 fragments that are not destroyed by the membrane attack complex (MAC) intravascularly can accumulate on the GPI-negative red blood cell (lacking CD55) surface and these fragments opsonize the red blood cells, causing reticuloendothelial destruction in the liver and spleen.(3)
The main clinical situations or diseases that should be considered in the differential diagnosis of PNH are:(3)
PNH is classified into three different categories:(3)
Patients with PNH have a median survival of ten years after diagnosis. The approach to therapy depends on the severity of symptoms and the degree of hemolysis. The treatment options for PNH are supportive care, allogenic hematopoietic stem cell transplantation (HCT) and a complement blockade.(2-3) |
Efficacy(1) |
Empaveli (pegcetacoplan) binds to complement protein C3 and its activation fragment C3b, thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation. In PNH extravascular hemolysis (EVH) is facilitated by C3b opsonization while intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex (MAC). Pegcetacoplan acts proximally in the complement cascade controlling both C3b-mediated EVH and terminal complement-mediated IVH.
The efficacy and safety of Empaveli in patients with PNH were assessed in a randomized, open-label, active comparator-controlled, 16-week Phase 3 study (Study APL2-302; NCT03500549). The study enrolled patients with PNH who had been treated with a stable dose of eculizumab for at least the previous 3 months and with hemoglobin levels less than 10.5 g/dL.
Eligible patients entered a 4-week run-in period during which they received Empaveli 1,090 mg subcutaneously twice weekly in addition to their current dose of eculizumab. Patients were then randomized in a 1:1 ratio to receive either 1,080 mg of Empaveli twice weekly or their current dose of eculizumab through the duration of the 16-week randomized controlled period. If required due to a lactate dehydrogenase (LDH) greater than 2 X the upper limit of normal (ULN), the dose of Empaveli could be adjusted to 1,080 mg every three days.
The efficacy of Empaveli was based on change from baseline to Week 16 (during randomized controlled period) in hemoglobin level. Baseline was defined as the average of measurements recorded prior to taking the first dose of Empaveli. Supportive efficacy data included transfusion avoidance, defined as the proportion of patients who did not require a transfusion during the randomized controlled period), and change form baseline to Week 16 in absolute reticulocyte count (ARC).
Empaveli was superior to eculizumab for the change from baseline in hemoglobin level at Week 16 (P less than 0.001). The adjusted mean change from baseline in hemoglobin level was 2.37 g/dL in the group treated with Empaveli versus -1.47 g/dL in the eculizumab group, demonstrating an adjusted mean increase of 3.84 g/dL with Empaveli compared to eculizumab at week 16 (95% CI, 2.33-5.34).
Non-inferiority was demonstrated in the endpoints of transfusion avoidance and change form baseline in ARC.
The results of the controlled trial of Empaveli in patients with PNH are supported by 2 uncontrolled studies in patients with PNH who were not receiving a complement inhibitor: Study APL2-202 (NCT03593200) and Study APL2-CP-PNH-204 (NCT02588833). In both studies, the treatment duration was approximately 1 year. Increases in hemoglobin were observed in these trials. |
Safety(1) |
Empaveli contains the following black box warnings:
Empaveli is contraindicated in:
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REFERENCES
Number |
Reference |
1 |
Empaveli Prescribing Information. Apellis Pharmaceuticals, Inc. May 2021. |
2 |
Sahin Fahri, Meltem Akay O, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines. Am J Blood Res. 2016; 6(2): 19-27. |
3 |
Rodolfo D. Cançado, Aderson da Silva Araújo, Alex Freire Sandes, Celso Arrais, Clarisse Lopes de Castro Lobo, Maria Stella Figueiredo, Sandra Fátima Menosi Gualandro, Sara Teresinha Olalla Saad, Fernando Ferreira Costa. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematology, Transfusion and Cell Therap. 2020. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Preferred Status |
Effective Date |
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Empaveli |
pegcetacoplan subcutaneous soln |
1080 MG/20ML |
M ; N ; O ; Y |
N |
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POLICY AGENT SUMMARY QUANTITY LIMIT
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
QL Amount |
Dose Form |
Day Supply |
Duration |
Addtl QL Info |
Allowed Exceptions |
Targeted NDCs When Exclusions Exist |
Effective Date |
|
||||||||||
Empaveli |
Pegcetacoplan Subcutaneous Soln |
1080 MG/20ML |
8 |
VIALS |
28 |
DAYS |
|
|
|
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CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Empaveli |
pegcetacoplan subcutaneous soln |
1080 MG/20ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
CLIENT SUMMARY – QUANTITY LIMITS
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Empaveli |
Pegcetacoplan Subcutaneous Soln |
1080 MG/20ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
QL with PA |
Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:
Length of Approval: 12 months NOTE: If approving for every three days dosing approve a quantity of 10 vials/30 days for 12 months
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This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.
Commercial _ PS _ Empaveli (pegcetacoplan) Prior Authorization with Quantity Limit _ProgSum_ 7/1/2023