PYRUKYND (mitapivat)

PYRUKYND (mitapivat)

Self-Administration – Oral

Diagnosis considered for coverage:

• Indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.

Coverage Criteria:

For diagnosis of hemolytic anemia in adults with pyruvate kinase (PK) deficiency:

• Dose does not exceed 50 mg twice daily, AND
• Patient is 18 years of age or older, AND
• Prescribed by or in consultation with a hematologist, AND
• 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), AND
• Diagnosis of pyruvate kinase deficiency confirmed by molecular testing of ALL the following mutations on the PKLR gene:
  • 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
  • Patients 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 10 g/dL, AND
• Patient has symptomatic anemia or is transfusion dependent, AND
• Exclusion of other causes of hemolytic anemias (e. g., infections, toxins, drugs)

Reauthorization Criteria:

For diagnosis of hemolytic anemia in adults with pyruvate kinase (PK) deficiency:

• Dose does not exceed 50 mg twice daily, AND
• Prescribed by or in consultation with a hematologist, AND
• Documentation of positive clinical response to therapy [e.g., hemoglobin greater than or equal to 1.5g/dL from baseline, reduction in transfusions, improvement in markers of hemolysis from baseline (e.g., bilirubin, lactated dehydrogenase [LDH], haptoglobin, reticulocyte count)]
  • If the patient does not meet medical necessity reauthorization criteria requirements, a 1-month authorization will be issued to allow for Pyrukynd gradual therapy discontinuation

Coverage Duration: 

• Initial: 6 months
• Reauthorization: 12 months

Authorization is not covered for the following:

The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.
 

Additional Information: 

• Dosing:
  • The starting dosage of Pyrukynd is 5 mg orally twice daily. To gradually increase hemoglobin (Hb), titrate Pyrukynd from 5 mg twice daily to 20 mg twice daily, and then to the maximum recommended dose of 50 mg twice daily, with these dose increases occurring every 4 weeks. Assess Hb and transfusion requirement before increasing to the next dose level, as some patients may reach and maintain normal Hb at 5 mg twice daily or 20 mg twice daily.
  • Discontinue Pyrukynd if no benefit has been observed by 24 weeks, based on the hemoglobin and hemolysis laboratory results and transfusion requirements.
  • To reduce the risk of acute hemolysis, avoid abrupt interruption or abrupt discontinuation of Pyrukynd when possible. Taper the dose to gradually discontinue the medication. Monitor patients for signs of acute hemolysis and worsening of anemia.

Current Dose            Dose Taper Schedule
                                 Day 1-7                    Day 8-14                Day 15
5 mg twice daily      5 mg once daily      Discontinue             N/A
20 mg twice daily    20 mg once daily    5 mg once daily       Discontinue
50 mg twice daily    50 mg once daily    20 mg once daily     Discontinue

Abbreviations: N/A = not applicable.

Policy Updates:

• 08/16/2022 – New policy approved by P&T.

References:

• Pyrukynd (mitapivat) [prescribing information]. Agios Pharmaceuticals, Inc. Cambridge, MA. 02139 
• 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. 
• 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. 
• UpToDate Pyruvate Kinase Deficiency. Available at https://www.uptodate.com/contents/pyruvate-kinase-deficiency. Accessed March 28, 2022. 
• 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.