Mitapivat (Pyrukynd) Form

Mitapivat (Pyrukynd®) is an pyruvate kinase (PK) activator.
FDA Approved Indication(s) Pyrukynd is indicated for the treatment of hemolytic anemia in adults with PK deficiency.
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 Pyrukynd is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Pyruvate Kinase Deficiency (must meet all):

1. Diagnosis of PK deficiency confirmed by one of the following (a or b): a. Presence of at least 2 mutant alleles in the PKLR gene, of which at least 1 is a missense mutation; b. Hemolytic anemia with laboratory evidence of reduced red blood cell PK enzymatic activity;
2. Prescribed by or in consultation with a hematologist;
   
   3. Age ≥ 18 years;
   4. Member is not homozygous for the R479H mutation or have 2 non-missense mutations (without the presence of another missense mutation);
3. If member received no more than 4 blood transfusions in the last 12 months, recent (within the last 30 days) hemoglobin concentration ≤ 10 g/dL;
4. Prescribed concurrently with oral folic acid;
   
   7. Dose does not exceed both of the following (a and b): a. 100 mg per day; b. 2 tablets per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):

5. 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): Page 1 of 6

   CLINICAL POLICY Mitapivat
   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

6. 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. Pyruvate Kinase Deficiency (must meet all):
7. 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);
8. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: a. Reduced transfusion burden; b. Increase in hemoglobin of at least 1.5 g/dL from baseline prior to Pyrukynd initiation;
9. If request is for a dose increase, new dose does not exceed both of the following (a and b): a. 100 mg per day; b. 2 tablets per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

10. 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 Page 2 of 6

    CLINICAL POLICY Mitapivat

11. 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 FDA: Food and Drug Administration PK: pyruvate kinase PKLR: pyruvate kinase liver and red blood cell Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings None reported
    Appendix D: General Information
    • Patients who were homozygous for the c.1436G>A (p.R479H) variant or had 2 non- missense variants (without the presence of another missense variant) in the PKLR gene were excluded in the clinical trial because these patients did not achieve hemoglobin response (change from baseline in Hb ≥ 1.5 g/dL at > 50% assessments) in the dose- ranging study. V. Dosage and Administration
    Indication Dosing Regimen PK deficiency Initial: 5 mg PO BID Maximum Dose 100 mg/day Dose may be increased every 4 weeks based on response and tolerance to 20 mg BID up to a maximum of 50 mg BID VI. Product Availability
    Oral tablets: 5 mg, 20 mg, 50 mg VII.