CurrentCignaPolicy IP0451

Pyrukynd (mitapivat) — Coverage Criteria for Pyruvate Kinase Deficiency

Cigna coverage policy for prescription benefit authorization and medical necessity criteria for Pyrukynd (mitapivat) to treat hemolytic anemia due to pyruvate kinase deficiency in adults.

Policy Summary

PayerCigna

PolicyPyrukynd (mitapivat) — Coverage Criteria for Pyruvate Kinase Deficiency

Policy CodePolicy IP0451

Change TypeMaterial revision — removal of Hb ≤12 g/dL requirement for continuing therapy (05/15/2025)

Effective DateMay 15, 2025

Next Review Date

Key ActionObtain prior authorization and document age, PKLR genetic test showing ≥2 variants (one missense), hemoglobin/hemolysis labs, and transfusion history.

SourceLink

POLICY UPDATE CHANGES

For patients currently receiving therapy, the requirement that the patient has a current hemoglobin level ≤ 12 g/dL was removed.

≥18min age

6 monthsinitial approval

1 yearcontinuation approval

≥2 PKLR variantsgenetic requirement

≤10 g/dL or ≥6 transfusions/yreligibility thresholds

Coverage Criteria for Pyrukynd (mitapivat)

FDA-Approved Indication

Approve for hemolytic anemia due to pyruvate kinase deficiency when the following criteria are met.

Indication options: Patient meets ONE of the following: A) Initial Therapy OR B) Currently Receiving Pyrukynd

A) Initial Therapy: Approve for 6 months if all of i-iv are met

Initial i: Patient is ≥ 18 years of age

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Initial ii: Presence of at least two variant/mutant alleles in the PKLR gene AND at least one is a missense variant

Policy Summary

PayerCigna

PolicyPyrukynd (mitapivat) — Coverage Criteria for Pyruvate Kinase Deficiency

Policy CodePolicy IP0451

Change TypeMaterial revision — removal of Hb ≤12 g/dL requirement for continuing therapy (05/15/2025)

Effective DateMay 15, 2025

Next Review Date

Key ActionObtain prior authorization and document age, PKLR genetic test showing ≥2 variants (one missense), hemoglobin/hemolysis labs, and transfusion history.

SourceLink

On This Page

Initial iii: Either: a) current hemoglobin level ≤ 10 g/dL OR b) currently receiving regular red blood cell transfusions (≥ 6 transfusions in last 12 months)

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Initial iv: Medication is prescribed by or in consultation with a hematologist

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B) Currently Receiving Pyrukynd: Approve for 1 year if all of i-iv are met

Current i: Patient is ≥ 18 years of age

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Current ii: Presence of at least two variant/mutant alleles in the PKLR gene AND at least one is a missense variant

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Current iii: Per prescriber, patient has experienced benefit evidenced by: a) increase in or maintenance of hemoglobin OR b) improvement in or maintenance of hemolysis laboratory parameters (e.g., indirect bilirubin, LDH, haptoglobin) OR c) decrease in or maintenance of transfusion requirements

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Current iv: Medication is prescribed by or in consultation with a hematologist

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Pyrukynd (mitapivat) is considered not medically necessary for any use other than the FDA‑approved indication of treatment for hemolytic anemia due to pyruvate kinase deficiency. Coverage is limited to the approved indication and uses outside that indication will not be covered.

Patients who are homozygous for the c.1436G>A (p.R479H) PKLR variant are excluded from coverage. These individuals were not included in pivotal studies of Pyrukynd because they did not achieve a hemoglobin response in the dose‑ranging study; therefore treatment with Pyrukynd is not covered for this genotype.

Patients with two non‑missense PKLR variants (without the presence of at least one missense variant) are excluded from coverage. Such patients were excluded from pivotal studies because they did not achieve a hemoglobin response in the dose‑ranging study; therefore treatment with Pyrukynd is not covered for this genetic profile.

Any use of Pyrukynd outside the FDA‑approved indication for hemolytic anemia due to pyruvate kinase deficiency is not medically necessary and will not be covered.

Coding and Clinical Thresholds

Covered CPT Codesmixed

No codes listed

inv-07: Hemoglobin threshold

Hemoglobin thresholdCurrent hemoglobin level ≤ 10 g/dL

ContextThreshold applies to initial therapy eligibility (approve for 6 months if met)

Source age requirementPatient must be ≥ 18 years of age to apply this threshold

inv-08: Regular transfusions

Regular transfusions (policy definition)At least six red blood cell transfusions within the last 12 months

Use in criteriaCounts as an alternative to hemoglobin ≤ 10 g/dL for initial therapy eligibility

Applies toInitial therapy determination (approve for 6 months)

Provider Actions, Authorization & Documentation

Prior Authorization

Prior Authorization Required

Prior Authorization is required for Pyrukynd. Initial approvals are provided for 6 months. Continuation (renewal) approvals are provided for 1 year when continuation criteria are met.

Initial approval duration: 6 months
Continuation approval duration: 1 year

Step Therapy

No additional step therapy requirements beyond the requirement that Pyrukynd be prescribed by or in consultation with a physician who specializes in the condition being treated (hematologist). Prior authorization is still required.

Specialist prescribing/consult requirement: hematologist
No other step edits specified

Documentation Required

Required Documentation

Prior authorization requests must include documentation supporting the covered indication and prescriber specialty/consultation. For initial requests include documentation of age (≥ 18 years), genetic testing showing presence of at least two PKLR variant/mutant alleles with at least one missense variant, baseline hemoglobin level or transfusion history, and evidence of hematology specialist prescribing or consultation. For continuation requests include documentation of genetic testing (if not previously provided), prescriber attestation of clinical benefit (for example: increase/maintenance of hemoglobin, improvement/maintenance of hemolysis labs such as indirect bilirubin, LDH, haptoglobin, or decreased/maintained transfusion requirements), and ongoing hematology specialist involvement. Approvals will be issued for the operational durations above; supporting clinical records, lab results and transfusion history should be provided as requested.

Initial request: age documentation (≥ 18 years)
Initial request: genetic testing showing ≥ 2 PKLR variant/mutant alleles with ≥ 1 missense variant
Initial request: baseline hemoglobin ≤ 10 g/dL OR transfusion history (≥ 6 transfusions in last year)
Initial request: documentation of hematologist prescribing or consultation
Continuation request: documentation of clinical benefit (increase/maintenance of hemoglobin; improvement/maintenance of hemolysis labs e.g., indirect bilirubin, LDH, haptoglobin; or decreased/maintenance of transfusion requirements)
Continuation request: hematologist prescribing or consultation documentation

Denial Risk

Billing / Code Denials

Claims submitted without covered diagnosis or procedure codes consistent with this Coverage Policy will be denied as not covered. Ensure coding aligns with the applicable benefit plan and the documented indication.

Claims lacking covered diagnosis/procedure codes will be denied as not covered

Background and Rationale

Pyruvate kinase deficiency is a rare, autosomal recessive red blood cell enzyme disorder caused by mutations in the PKLR gene that lead to reduced pyruvate kinase activity and variable hemolytic anemia. Clinical manifestations range from mild to severe hemolysis and may include complications such as iron overload, gallstones, pulmonary hypertension, thrombosis, and extramedullary hematopoiesis. Management historically includes supportive care such as transfusions, splenectomy, and iron chelation; Pyrukynd (mitapivat) is a pyruvate kinase activator indicated for adults with hemolytic anemia due to pyruvate kinase deficiency.

Definitions

inv-14: Pyruvate kinase deficiency

DefinitionPyruvate kinase deficiency is a rare autosomal recessive enzyme defect in red blood cells caused by mutations in the PKLR gene leading to reduced pyruvate kinase activity and variable hemolytic anemia.

EpidemiologyEstimated prevalence three to nine cases per one million people (rare).

Genetic causeCaused by mutations in the pyruvate kinase liver and red blood cell (PKLR) gene; most patients have compound heterozygous mutations and commonly at least one missense mutation.

inv-15: Regular transfusions (policy definition)

Policy definitionRegular transfusions are defined as at least six red blood cell transfusions within the last year.

Role in coverageMeets one of the eligibility options for initial therapy when present (alternative to hemoglobin ≤ 10 g/dL).

Documentation expectedTransfusion history over the prior 12 months should be documented for prior authorization.

Operational note: approvals issued for 6 months (initial) or 1 year (continuation)