WHA
 

Mitapivat Products

Indications for Prior Authorization

Pyrukynd (mitapivat)
  • For diagnosis of Hemolytic Anemia with Pyruvate Kinase (PK) Deficiency
    Indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.

Aqvesme (mitapivat)
  • For diagnosis of Anemia with alpha- or beta-thalassemia
    Indicated for the treatment of anemia in adults with alpha- or beta-thalassemia.

Criteria

Pyrukynd

Prior Authorization (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Hemolytic Anemia with Pyruvate Kinase (PK) Deficiency

  • Diagnosis of hemolytic anemia confirmed by the presence of chronic hemolysis (e.g., increased indirect bilirubin, elevated lactated dehydrogenase [LDH], decreased haptoglobin, increased reticulocyte count) [A, 2, 3, 4]
    • AND
  • Diagnosis of pyruvate kinase deficiency confirmed by molecular testing of ALL the following mutations on the PKLR gene: [B, 1, 2, 4, 5]
    • Presence of at least 2 variant alleles in the pyruvate kinase liver and red blood cell (PKLR) gene, of which at least 1 was a missense variant
    • Patient is not homozygous for the c.1436G>A (p.R479H) variant
    • Patient does not have 2 non-missense variants (without the presence of another missense variant) in the PKLR gene
    AND
  • Hemoglobin is less than or equal to 10g/dL [1]
    • AND
  • Patient has symptomatic anemia or is transfusion dependent [7]
    • AND
  • Other causes of hemolytic anemias (e.g., infections, toxins, drugs) have been excluded [C, 2, 5]
    • AND
  • Prescribed by or in consultation with a hematologist
Pyrukynd

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Hemolytic Anemia with Pyruvate Kinase (PK) Deficiency

  • Patient demonstrates positive clinical response to therapy [e.g., hemoglobin increase greater than or equal to 1.5g/dL from baseline, reduction in transfusions of greater than or equal to 33% in the number of red blood cell units transfused during the fixed dose period compared with the patient's historical transfusion burden, improvement in markers of hemolysis from baseline (e.g., bilirubin, lactated dehydrogenase [LDH], haptoglobin, reticulocyte count)]
    • AND
  • Prescribed by or in consultation with a hematologist
Aqvesme

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Anemia with alpha- or beta-thalassemia

  • Diagnosis of anemia with alpha or beta-thalassemia
    • AND
  • Hemoglobin is less than or equal to 10g/dL [10-11]
    • AND
  • Patient has symptomatic anemia or is transfusion dependent
    • AND
  • Patient does not have liver disease (e.g., cirrhosis - Child Pugh Class A, B, or C; Hep B virus [HBV], Hepatitis C virus [HCV], Human Immunodeficiency virus [HIV-1 or HIV -2]) [D, 9-11]
    • AND
  • Both of the following: [10-11]
    • Patient has not had prior exposure to gene therapy for alpha or beta thalassemia (e.g.,Casgevy, Zynteglo)
    • Patient has not had prior bone marrow or stem cell transplantation
    AND
  • Patient is not on concurrent treatment with any of the following: [10- 11]
    • Reblozyl (luspatercept-aamt)
    • Hematopoietic stimulating agents (e.g., Epogen [epoetin alfa], Aranesp [darbepoetin alfa])
    • Pyrukynd (mitapivat)
    AND
  • Prescribed by or in consultation with one of the following:
    • hematologist
    • hepatologist
Aqvesme

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Anemia with alpha- or beta-thalassemia

  • Patient demonstrates positive clinical response to therapy (e.g., reduction in RBC transfusion burden, improvement in fatigue, increase in Hb concentration greater than or equal to 1g/dL from baseline)
    • AND
  • Prescribed by or in consultation with one of the following:
    • hematologist
    • hepatologist
    AND
  • Patient is not on concurrent treatment with any of the following:
    • Reblozyl (luspatercept-aamt)
    • Hematopoietic stimulating agents (e.g., Epogen [epoetin alfa], Aranesp [darbepoetin alfa])
    • Pyrukynd (mitapivat)

  • Guideline ID
    GL-503324

  • Formulary
    Premium

  • Effective date
    Mar 1, 2026

  • P&T approval date
    May 19, 2022

P & T Revisions

2026-02-03, 2025-03-13, 2024-04-01, 2023-11-30, 2023-04-12, 2022-08-17, 2022-05-24

  1. Pyrukynd (mitapivat) [prescribing information]. Agios Pharmaceuticals, Inc. Cambridge, MA. February 2022.
  2. Bianchi, P., Fermo, E. et al. Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency. Available at https://doi.org/10.1002/ajh.25325. October 25, 2018. Accessed March 28, 2022.
  3. National Organization for Rare Disorders and Foundation for Rare Blood Diseases. Voice of the Patient Report Pyruvate Kinase Deficiency. Available at https://rarediseases.org/wp-content/uploads/2020/01/NRD-2029-Voice-of-the-Patient-Report-PKD_FNL-1.pdf. Accessed March 28,2022.
  4. UpToDate Pyruvate Kinase Deficiency. Available at https://www.uptodate.com/contents/pyruvate-kinase-deficiency. Accessed April 1, 2024.
  5. Samkari-Al, H., Van Beers, E. et al. The variable manifestations of disease in pyruvate kinase deficiency and their management. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556504/. Accessed March 28, 2022.
  6. Clinical consult April 8, 2022.
  7. May P & T Committe feedback. May 19, 2022.
  8. Samkari, H., Shehata, N., Robertson, K., et al. Diagnosis and management of pyruvate kinase deficiency: international expert guidelines. Available at : https://thalassaemia.org.cy/wp-content/uploads/2024/03/PKD-Guidelines-LancetHaem-02-2024-1.pdf. Accessed April 1, 2024.
  9. Aqvesme (mitapivat) [prescribing information]. Agios Pharmaceuticals, Inc. Cambridge, MA. December 2025.
  10. ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) (ENERGIZE-T). Available at: https://www.clinicaltrials.gov/study/NCT04770779?cond=(NCT04770779)&rank=1#participation-criteria. Accessed January 19, 2026.
  11. ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT). Available at: https://www.clinicaltrials.gov/study/NCT04770753?cond=NCT04770753&rank=1#participation-criteria. Accessed January 19, 2026.
  12. Aqvesme Drug Website. Available at: https://www.aqvesme.com/thalassemia/. Accessed January 19, 2026.
  13. UptoDate: Management of thalassemia. Available at: https://www.uptodate.com/contents/management-of-thalassemia?search=aqvesme&source=search_result&selectedTitle=3~9&usage_type=default&display_rank=2. Accessed January 19, 2026.
  1. The first step in the evaluation of a person with possible PK deficiency is to establish if hemolysis is present. Hemolytic anemia is characterized by an increased reticulocyte count, increased indirect bilirubin, and possibly by increased LDH and decreased haptoglobin [4]
  2. In case of decreased PK activity, sequencing of PKLR gene is highly recommended to confirm the diagnosis [2]
  3. Since the hematological features of PK deficiency are not specific, the possibility of PK deficiency and other metabolic abnormalities should be considered in all patients displaying chronic hemolysis where an immune-mediated hemolytic process, red cell membrane defect, unstable hemoglobin, or paroxysmal nocturnal hemoglobinuria has been excluded [2]
  4. Aqvesme can cause hepatocellular injury. Avoid use of Aqvesme in patients with cirrhosis. In patients with thalassemia treated with Aqvesme, liver injury with and without jaundice has been observed within the first 6 months of exposure. Obtain liver tests (including ALT, AST, alkaline phosphatase, total bilirubin with fractionation) prior to the initiation of Aqvesme, then every 4 weeks for the first 24 weeks, and as clinically indicated thereafter. [9]
  • 2026-02-03: Update Guideline for new UM PA program for Aqvesme
  • 2025-03-13: Addition of EHB formulary to guideline.
  • 2024-04-01: 2024 Annual Review
  • 2023-11-30: Program update to standard reauthorization language. No changes to clinical intent.
  • 2023-04-12: 2023 Annual Review
  • 2022-08-17: Update Um Criteria
  • 2022-05-24: New PA criteria