Pharmacy Prior Authorization Criteria

Pyrukynd (mitapivat)

Indications for Prior Authorization

Pyrukynd (mitapivat)

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

Criteria

Pyrukynd

Prior Authorization (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Hemolytic Anemia

• 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
• 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 10g/dL [1]
AND
• Patient has symptomatic anemia or is transfusion dependent [7]
AND
• Exclusion of other causes of hemolytic anemias (e. g., infections, toxins, drugs) [C, 2, 5]
AND
• Prescribed by or in consultation with a hematologist

Pyrukynd

If the member does not meet the medical necessity reauthorization criteria requirements, a denial should be issued and a 1-month authorization should be issued one time for Pyrukynd gradual therapy discontinuation.

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Hemolytic Anemia

• 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

P & T Revisions

2024-04-01, 2023-11-30, 2023-04-12, 2022-08-17, 2022-05-24

References

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.

---

End Notes

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]

---

Revision History

• 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

---