CurrentUnitedHealthcarePolicy N/A

Pyrukynd (mitapivat) prior authorization

Defines prior authorization and medical necessity criteria for Pyrukynd (mitapivat) for treatment of hemolytic anemia due to pyruvate kinase (PK) deficiency for UnitedHealthcare members.

Policy Summary

PayerUnitedHealthcare

PolicyPyrukynd (mitapivat) prior authorization

Policy CodePolicy N/A

Change TypeRevised — material

Effective DateAug 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and document at least 2 PKLR variant alleles (≥1 missense) plus required hematologic/transfusion criteria to support a 12-month approval.

SourceLink

POLICY UPDATE CHANGES

Updated initial approval duration from 6 months to 12 months and simplified reauthorization criteria.

12 monthsinitial authorization duration

12 monthsreauthorization with response

4 weekstitration authorization

≥2 allelesgenetic requirement

Hb ≤10 g/dLhematologic threshold

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Coverage Criteria

Initial Authorization

Covered when ALL of the following are met

Initial Authorization: Diagnosis of pyruvate kinase (PK) deficiency based on genetic testingPresence of at least 2 variant alleles in the PKLR gene, of which at least 1 is a missense; patient is not homozygous for c.1436G>A (p.R479H); patient does not have 2 non-missense variants without another missense variant

Genetic testing report required (document variant alleles and variant types)

Indication: Used for the treatment of hemolytic anemia

Hematologic criteria: Either hemoglobin/transfusion criteria OR high transfusion burden(1) Both: baseline hemoglobin ≤ 10 g/dL AND no more than 4 transfusions in the prior 52 weeks with none in the preceding 3 months; OR (2) at least 6 transfusion episodes in the preceding 52 weeks

Document baseline hemoglobin and transfusion history for prior 52 weeks (including timing of last transfusion)

Prescriber specialty: Prescribed by a nephrologist or hematologist

Authorization will be issued for 12 months when criteria met

Reauthorization

Reauthorization criteria — two pathways

Reauthorization - clinical response: Documentation of positive clinical response to Pyrukynd therapy and prescribed by, or in consultation with, a nephrologist or hematologist

Authorization will be issued for 12 months

Reauthorization - no documented response: Documentation does not provide evidence of positive clinical response to Pyrukynd therapy; allow for dose titration with discontinuation of therapy

Authorization will be issued for 4 weeks to allow dose titration

Patients who are homozygous for the c.1436G>A (p.R479H) variant are excluded from coverage under the genetic criteria and do not meet the policy’s diagnostic requirement for pyruvate kinase (PK) deficiency.

Use of Pyrukynd (mitapivat) without documentation of the required PKLR genetic findings — specifically at least 2 PKLR variant alleles with at least 1 missense variant (and not meeting the exclusions such as homozygosity for c.1436G>A [p.R479H] or two non-missense variants without another missense) — is not supported by the coverage criteria. Likewise, therapy is not supported when the hematologic/transfusion thresholds are not met (for example, baseline hemoglobin ≤ 10 g/dL with ≤ 4 transfusions in the prior 52 weeks and none in the preceding 3 months, or alternatively ≥ 6 transfusion episodes in the prior 52 weeks).

Coding and Baseline Requirements

Baseline hemoglobin — threshold

Baseline hemoglobin threshold≤ 10 g/dL

Context in criteriaRequired as part of hematologic enrollment pathway when combined with limited recent transfusions

Measurement timingBaseline value documented prior to initiation

Transfusion history — prior 52 weeks

Primary transfusion pathwayNo more than 4 transfusions in the previous 52 weeks AND no transfusions in the preceding 3 months

Alternate high-burden pathwayMinimum of 6 transfusion episodes in the preceding 52 weeks

Look-back period

Provider Actions and Administrative Controls

Prior Authorization

Prior Authorization Required

Prior Authorization Required: Prior authorization is required for Pyrukynd. Initial authorization will be issued for 12 months when all criteria are met.

Initial authorization duration: 12 months
Prescriber requirement: nephrologist or hematologist

Note

Program-level Controls

Program-level controls may apply. UnitedHealthcare may use automated approval and re-authorization processes based on prior claim/medication history, diagnosis codes (ICD-10), and claim logic. Supply limits may be in place.

Automated approval/re-approval may be used depending on program or therapeutic class
Supply limits may apply

Background

Mitapivat (Pyrukynd) is a pyruvate kinase activator indicated for treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. The policy requires genetic confirmation of PK deficiency — presence of at least 2 PKLR variant alleles with at least 1 missense variant and exclusion of certain genotypes (including homozygosity for c.1436G>A [p.R479H]) — and defines hematologic enrollment thresholds by either baseline hemoglobin and limited recent transfusion history or by a high transfusion burden. When the diagnostic and hematologic/transfusion criteria and prescriber specialty requirements are met, prior authorization is granted for an initial 12-month approval.

Definitions

PK deficiency diagnosis — genetic definition

Genetic diagnostic requirementPresence of at least 2 variant alleles in the PKLR gene with at least 1 missense variant

Exclusion — specific homozygosityPatients homozygous for c.1436G>A (p.R479H) are excluded

Exclusion — variant type combinationTwo non-missense PKLR variants without an additional missense variant do not meet the diagnostic criterion

Initial Therapy Criteria

Initial Therapy

Initial authorization requirements

Genetic confirmation: At least 2 PKLR variant alleles with at least 1 missense; patient is not homozygous for c.1436G>A (p.R479H); patient does not have 2 non-missense variants without another missense

Genetic testing report required

Indication and prescriber: Used for treatment of hemolytic anemia and prescribed by a nephrologist or hematologist

Initial authorization will be issued for 12 months when criteria met

Hematologic/transfusion criteria: Either hemoglobin ≤10 g/dL with limited transfusion history OR ≥6 transfusion episodes in the prior 52 weeks(1) Both: baseline hemoglobin ≤10 g/dL AND no more than 4 transfusions in the previous 52 weeks with none in the preceding 3 months; OR (2) minimum of 6 transfusion episodes in the preceding 52 weeks

Continuation / Reauthorization Criteria

Reauthorization/Continuation

Reauthorization pathways

Continuation with response: Documentation of positive clinical response to Pyrukynd therapy

Authorization will be issued for 12 months

Continuation without response: If documentation does not demonstrate a positive clinical response, allow for dose titration with the possibility of discontinuation of therapy

Authorization will be issued for 4 weeks to allow dose titration/discontinuation

Quantity Limits

Pyrukynd (mitapivat) — supply/quantity controls

Quantity limitsSupply limits may be in place per program rules

Automated approvalsUse of automated approval and re-approval processes varies by program and therapeutic class

Program variationProgram-level controls may modify authorization and supply rules