Empaveli (pegcetacoplan) Form

Overview Clinical criteria Overview Coding Document history References This document addresses the use of Empaveli (pegcetacoplan), a subcutaneously administered peptide that targets complement C3. It is FDA approved for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH).
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder associated with a variety of nonspecific clinical features including but not limited to hemolytic anemia, fatigue, smooth muscle dystonia, and atypical venous thrombosis. Treatment options are limited but may include the use of therapeutic anticoagulation, allogeneic hematopoietic cell transplantation and/or complement inhibitors (Soliris or Ultomiris) depending upon symptom severity, degree of hemolysis, and history of thrombosis. Soliris and Ultomiris target complement C5 and are used to reduce intravascular hemolysis, decrease or eliminate the need for blood transfusions, and reduce the risk for thrombosis. Despite C5 inhibition, some patients continue to experience extravascular hemolysis, manifesting as persistent anemia, due to a separate complement C3 pathway. Empaveli is the first subcutaneous treatment option and the first agent to target extravascular hemolysis. Current published evidence includes one phase 3, open-label, controlled trial that included individuals with hemoglobin levels lower than 10.5 g per deciliter and recent transfusion despite stable eculizumab therapy (Hillmen 2021). Compared to individuals continuing treatment with eculizumab, those treated with Empaveli achieved an adjusted mean hemoglobin increase of 3.84 g/dL at week 16. Another phase 3, open-label, controlled trial included individuals with PNH who were complement-inhibitor naïve with Lactate dehydrogenase (LDH) ≥1.5 times the upper limit of normal and hemoglobin level below the lower limit of normal (Wong 2023). Individuals treated with Empaveli achieved hemoglobin stabilization and a greater decrease in LDH level compared to individuals receiving supportive care.
Empaveli is available in 20 mL single use vials for subcutaneous use. It is administered by subcutaneous infusion twice weekly (i.e. day 1 and day 4 of each week) via a commercially available infusion pump with a reservoir or via the Empaveli on-body injector. Individuals with a lactate dehydrogenase (LDH) level greater than 2x the upper limit of normal may adjust the dosing frequency to every 3 days. If complement inhibitor therapy is discontinued, individuals should be closely monitored for at least 8 weeks after cessation to detect hemolysis. The prescribing information includes instructions for individuals switching to Empaveli from C5 inhibitors. If switching from Solirirs (eculizumab), initiate Empaveli while continuing eculizumab at its current dose for 4 weeks. After 4 weeks, discontinue eculizumab and continue monotherapy with Empaveli. If switching from Ultomiris (ravulizumab), initiate Empaveli no more than 4 weeks after the last dose of ravulizumab. No overlap therapy is recommended with ravulizumab. Empaveli (pegcetacoplan) has a black box warning for serious infections caused by encapsulated bacteria. Meningococcal infections may occur in patients treated with Empaveli and may become rapidly life-threating or fatal if not recognized and treated early. Use of Empaveli may predispose individuals to serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B. Individuals should be immunized, according to most current Advisory Committee on Immunization Practices (ACIP) recommendations, against encapsulated bacteria at least 2 weeks prior to administering the first dose unless the risk of delaying therapy outweigh the risk of developing a serious infection. The FDA has required the manufacturer to develop comprehensive risk management programs that include the enrollment of prescribers in the Empaveli REMS Program. Additional information and forms for individuals, prescribers, and pharmacists may be found on the manufacturer’s website: https://www.empaveli.com. Clinical Criteria When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose. Empaveli (pegcetacoplan) Initial requests for Empaveli (pegcetacoplan) may be approved if the following criteria are met: 1

I. II. Individual is 18 years of age or older; AND Individual has a diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH) as verified by flow cytometry, including the presence of (Parker 2005): A. PNH type III red cell clone or a measurable granulocyte or monocyte clone; OR B. Glycosylphosphatidylinositol-anchored proteins (GPI-AP)-deficient polymorphonuclear cells (PMNs);
AND III. AND IV. Individual has been immunized against encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B at least 2 weeks prior to administration of the first dose of Empaveli (pegcetacoplan), unless the risks of delaying Empaveli outweigh the risk of developing a bacterial infection with an encapsulated organism;
One of the following applies (A or B): A. Individual is complement inhibitor treatment naïve (i.e. not switching from eculizumab or ravulizumab) (Wong 2023); AND

2. Individual has lactate dehydrogenase greater than or equal to 1.5 times the upper limit of normal, and documentation is provided; AND Individual has one or more PNH-related sign or symptom (such as but not limited to anemia, history of a major adverse vascular event from thromboembolism, or history of transfusion due to PNH); OR B. Documentation is provided that individual is switching from treatment with eculizumab or ravulizumab (Hillmen 2021); AND
   A. B. If on eculizumab, treatment with eculizumab will be discontinued 4 weeks after Empaveli initiation, OR If on ravulizumab, treatment with ravulizumab will be discontinued prior to Empaveli initiation.
   Initial Approval Duration: 6 months Continuation requests for Empaveli (pegcetacoplan) may be approved if the following criteria are met: I. Documentation is provided that individual has experienced a clinical response as shown by one of the following (Hillmen 2021): A. Stabilization of hemoglobin levels; OR B. Reduction in number of transfusions required; OR C. Improvement in hemolysis (for example, normalization or decrease of LDH levels); AND Individual is not using in combination with Soliris (eculizumab) or Ultomiris (ravulizumab). II. Requests for Empaveli (pegcetacoplan) may not be approved for the following: I. II. Individual is using in combination with Soliris (eculizumab) or Ultomiris (ravulizumab) [with the exception of a 4-week overlap for individuals switching from eculizumab to pegcetacoplan]; OR Individual has evidence of an active infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type B. Quantity Limits Empaveli (pegcetacoplan) Quantity Limits Empaveli (pegcetacoplan) 1080 mg/20 mL (54 mg/mL) vial Drug 10 vials per 30 days Limit Coding The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. HCPCS
   J3490 C9399 ICD-10 Diagnosis Unclassified drugs (when specified as [Empaveli]) Unclassified drugs or biologicals (When specified as [Empaveli]) 2

   All diagnoses pend Document History Revised: 11/17/2023