Corporate Medical Policy: Crovalimab-akkz (PiaSky™) “Notification”

Restricted Product(s):

• crovalimab-akkz (PiaSky™) intravenous infusion and subcutaneous injection for administration by a healthcare professional

FDA Approved Use:

• For treatment of adult and pediatric patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) and body weight of at least 40 kg

Criteria for Medical Necessity:

The restricted product(s) may be considered medically necessary when the following criteria are met:

Initial Criteria for Approval:

1. The patient is 13 years of age or older and weighs at least 40 kg [medical record documentation required]; AND
2. The patient has a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) [medical record documentation required]; AND
3. The diagnosis has been confirmed by ALL of the following:
   1. Flow cytometry with at least two independent flow cytometry reagents on at least two cell lineages (e.g., red blood cells [RBCs] and granulocytes) demonstrating that the patient’s peripheral blood cells are deficient in glycosylphosphatidylinositol (GPI)-linked proteins [medical record documentation required]; AND
   2. Laboratory results showing a lactate dehydrogenase (LDH) level ≥ 2 times the upper limit of normal at baseline prior to starting complement inhibitor therapy [medical record documentation required]; AND
   3. The patient has at least one PNH-related sign or symptom in the past 3 months prior to starting complement inhibitor therapy (e.g., fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin < 10 g/dL], history of a major adverse vascular event [including thrombosis], dysphagia, erectile dysfunction, or history of RBC transfusion due to PNH) [medical record documentation required]; AND
4. ONE of the following:
   1. The patient has tried and had an inadequate response to TWO of the following: iptacopan (Fabhalta), pegcetacoplan (Empaveli), ravulizumab-cwvz (Ultomiris) [medical record documentation required]; OR
   2. The patient has an intolerance or hypersensitivity to TWO of the following: iptacopan (Fabhalta), pegcetacoplan (Empaveli), ravulizumab-cwvz (Ultomiris) [medical record documentation required]; OR
   3. The patient has an FDA labeled contraindication to ALL of the following: iptacopan (Fabhalta), pegcetacoplan (Empaveli), ravulizumab-cwvz (Ultomiris) [medical record documentation required]; AND
5. The patient will NOT be using the requested agent in combination with another complement inhibitor used to treat PNH (e.g., eculizumab, iptacopan, pegcetacoplan, ravulizumab) [medical record documentation required]; AND
6. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., hematologist) or has consulted with a specialist in the area of the patient’s diagnosis [medical record documentation required]; AND
7. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
8. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 180 days (6 months)

Continuation Criteria for Approval:

1. The patient was approved through Blue Cross NC initial criteria for approval; OR
2. The patient would have met initial criteria for approval at the time they started therapy; AND
3. The patient has had either stabilization or improvement of symptoms from baseline while using the requested agent (e.g., significant reduction in RBC transfusion requirements, stabilization/improvement of hemoglobin, reduction of LDH, no thromboembolism events persisting while using the requested agent, stabilization/improvement of symptoms) [medical record documentation required]; AND
4. The patient will NOT be using the requested agent in combination with another complement inhibitor used to treat PNH (e.g., eculizumab, iptacopan, pegcetacoplan, ravulizumab) [medical record documentation required]; AND
5. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., hematologist) or has consulted with a specialist in the area of the patient’s diagnosis [medical record documentation required]; AND
6. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
7. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year)

*Maximum units allowed for duration of approval

*Site of Care Medical Necessity Criteria:

1. For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR
2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met:
   1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR
   2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR
   3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR
   4. Re-initiation of therapy, defined as ONE of the following:
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR
   5. Requirement of a change in the requested restricted product formulation; AND
3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.

References: all information referenced is from FDA package insert unless otherwise noted below.

1. Borowitz MJ, Craig FE, DiGiuseppe JA, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry Part B (Clinical Cytometry). 2010;78B:211-230.
2. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699-3709.

Policy Implementation/Update Information: Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee,regardless of change. This policy is reviewed in Q2 annually.

February 2025: Criteria change: Added requirement for trial and failure of two of the following: iptacopan (Fabhalta), pegcetacoplan (Empaveli), ravulizumab-cwvz (Ultomiris). Policy notification given 12/2/2024 for effective date 2/1/2025.

January 2025: Coding change: Added HCPCS code J1307 to dosing reference table effective 1/1/2025; deleted C9399, J3490, and J3590 termed 12/31/2024. Adjusted maximum units according to coding unit definition for clarity.

September 2024: Original medical policy criteria issued.