CurrentBlue Cross Blue Shield - IowaPolicy 05.04.62

Pyrukynd (mitapivat) for pyruvate kinase deficiency

Defines prior authorization criteria, documentation requirements, initial and continuation approval criteria, dosing/quantity limits, and billing guidance for Pyrukynd (mitapivat) for treatment of hemolytic anemia due to pyruvate kinase (PK) deficiency for Wellmark Blue Cross and Blue Shield members.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyPyrukynd (mitapivat) for pyruvate kinase deficiency

Policy CodePolicy 05.04.62

Change TypeReviewed; no material clinical changes

Effective DateApr 9, 2023

Next Review Date

Key ActionSubmit chart notes or medical record documentation showing genetic testing or enzyme assay confirming PK deficiency, plus transfusion history or hemoglobin data for prior authorization.

POLICY UPDATE CHANGES

Policy reviewed October 2024; revised January 2023; current effective date April 9, 2023.

1FDA-approved indication(s)

6 monthsTypical approval duration

>=6Transfusions threshold (52 wks)

>=1.5 g/dLHemoglobin response threshold

Coverage Summary

Covered with criteria: Pyrukynd (mitapivat) is covered for treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency when the policy's approval criteria are met. This stance aligns with the FDA-approved indication for Pyrukynd and is consistent with product labeling, clinical studies, and compendial uses. Genetic testing (>=2 PKLR mutant alleles with >=1 missense) or an enzyme assay demonstrating PK enzyme deficiency is required for confirmation of diagnosis.

Key thresholds and quick facts

Age>= 18 years

Hemoglobin (initial approval)<= 10.0 g/dL

Transfusion history>= 6 blood transfusion episodes in past 52 weeks

Hemoglobin response (continuation)>= 1.5 g/dL increase from baseline

Concomitant therapy>= 0.8 mg oral folic acid daily

Typical approval duration6 months

FDA-approved indication(s)1 (treatment of hemolytic anemia in adults with PK deficiency)

Initial Therapy Criteria (Medically Necessary)

Initial Therapy / Medically Necessary

Pyrukynd (mitapivat) may be considered medically necessary when ALL of the following are met:

ALL of the following

Genetic or enzymatic confirmation (ONE of)
- Deficiency of PK enzyme activity (enzyme assay demonstrating deficiency of PK enzyme activity)
- Presence of at least 2 mutant alleles in the PKLR gene, of which at least 1 is a missense mutation (genetic testing)
Member is not homozygous for the R479H mutation or does not have 2 non-missense variants, without the presence of another missense mutation, in the PKLR gene
Clinical severity criteria (ONE of)
- History of a minimum of 6 blood transfusion episodes in the past 52 weeks>= 6 blood transfusion episodes in past 52 weeks
- Hemoglobin (Hb) concentration less than or equal to 10.0 g/dL<= 10.0 g/dL
Member is receiving concomitant treatment with at least 0.8 mg oral folic acid daily>= 0.8 mg oral daily
Prescribed by or in consultation with a hematologist
Member is 18 years of age or older>= 18 years

Prior Authorization

Prior authorization and documentation for initial requests

Submit chart notes or medical record documentation showing genetic testing (>=2 mutant PKLR alleles with >=1 missense) or enzyme assay demonstrating PK deficiency; documentation that member is not homozygous R479H or does not have 2 non-missense variants without another missense; and blood transfusion history or hemoglobin data.

Genetic testing: documentation of at least 2 mutant PKLR alleles with at least 1 missense mutation
Enzyme assay: assay demonstrating deficiency of PK enzyme activity
Documentation that member is not homozygous for R479H or does not have two non-missense variants without another missense mutation
Blood transfusion history (e.g., number of transfusion episodes in past 52 weeks) or hemoglobin data (e.g., Hb concentration)

Continuation Therapy Criteria (Medically Necessary)

Continuation of Therapy / Medically Necessary

Pyrukynd (mitapivat) may be considered medically necessary for continued treatment when ALL of the following are met:

ALL of the following

Response (ONE of)
- Increase in hemoglobin of at least 1.5 g/dL from baseline>= 1.5 g/dL
- Reduction in blood transfusions from baseline
Member will continue to receive concomitant treatment with at least 0.8 mg oral folic acid daily>= 0.8 mg oral daily
Prescribed by or in consultation with a hematologist

Prior Authorization

Documentation for continuation requests

Provide chart notes documenting a positive clinical response defined as either increase in hemoglobin >=1.5 g/dL from baseline or reduction in blood transfusions from baseline.

Chart notes documenting increase in hemoglobin of at least 1.5 g/dL from baseline
Or chart notes documenting reduction in blood transfusions from baseline

Billing Rule

Approval duration

Initial approvals: approval will be for 6 months.

Unproven / Not Medically Necessary

Not Medically Necessary

Pyrukynd (mitapivat) is considered not medically necessary when the above criteria are not met.

Member does not meet all criteria for initial or continuation approval as specified

Denial Risk

Denial risk for missing required documentation or criteria

Claims may be denied if required genetic or enzymatic confirmation is not provided, if the member does not meet transfusion (>=6 in past 52 weeks) or hemoglobin (<=10.0 g/dL) thresholds for initial approval, or if documentation of the defined positive clinical response for continuation is not submitted.

Provider Actions & Requirements

Documentation Required

Prescriber requirement

Drug must be prescribed by or in consultation with a hematologist.

Prior authorization — required documentation and steps:

• Diagnostic confirmation: Submit chart notes or medical records showing either an enzyme assay demonstrating PK enzyme deficiency OR genetic testing showing at least 2 mutant PKLR alleles with at least 1 missense.

• Variant status: Document that the member is not homozygous for R479H and does not have 2 non-missense variants without another missense in PKLR.

• Clinical severity: Provide blood transfusion history (e.g., ≥6 transfusions in past 52 weeks) or hemoglobin values (e.g., Hb ≤ 10.0 g/dL) as applicable.

• Prescriber: Drug must be prescribed by or in consultation with a hematologist.

• Approval duration: Initial approvals will be for 6 months.

Background

Background and scope: Pyrukynd (mitapivat) is FDA-approved for treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. The policy is intended to ensure appropriate patient selection based on product labeling, clinical studies, and compendial uses, and requires genetic or enzymatic confirmation of PK deficiency prior to approval.

Definitions: Positive clinical response — an increase in hemoglobin of at least 1.5 g/dL from baseline OR a reduction in blood transfusions from baseline.

Revision History

2023-01revised

Policy revised January 2023; revision noted in policy history. No material clinical changes indicated.

2023-04-09effective

Current effective date April 9, 2023.

2024-10reviewedLatest

Policy reviewed October 2024; document indicates no newly material clinical changes.