CurrentCignaPolicy N/A

Pyrukynd (mitapivat) prior authorization for pyruvate kinase deficiency

Defines prior authorization criteria, documentation requirements, coverage durations, and exclusions for Pyrukynd (mitapivat tablets) for treatment of hemolytic anemia due to pyruvate kinase (PKLR) deficiency for Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyPyrukynd (mitapivat) prior authorization for pyruvate kinase deficiency

Policy CodePolicy N/A

Change TypeAnnual revision (no criteria changes)

Effective Date

Next Review Date

Key ActionPrior authorization is required; provide genetic testing documentation showing at least two PKLR variants with at least one missense variant and document clinical benefit for continuation.

POLICY UPDATE CHANGES

Annual Revision, Summary of Changes = No criteria changes (02/19/2025).

02/28/2024 revision removed requirement that patients currently receiving therapy have current hemoglobin ≤ 12 g/dL (historical).

1Covered Indication(s)

≥18Age restriction

6 moInitial approval duration

1 yrContinuation approval duration

Coverage Summary

Pyrukynd (mitapivat) is indicated for treatment of hemolytic anemia due to pyruvate kinase (PKLR) deficiency in adults. Coverage applies to Cigna-administered health benefit plans and requires prior authorization; approvals are provided for specified durations (initial approvals typically for 6 months, continuing approvals for 1 year). The policy defines the intended population as adults aged ≥ 18 years with documented PKLR gene variants and specifies payer-level documentation and specialist prescriber requirements.

Age≥ 18 years

Hemoglobin≤ 10 g/dL (initial therapy eligibility)

Transfusion frequency≥ 6 transfusions in the last year (regular transfusions)

Trial duration to assess benefit24 weeks (discontinue if no benefit)

Initial Therapy Criteria

A) Initial Therapy

Pyrukynd is covered as medically necessary when criteria below are met for FDA-approved indication(s). Approvals provided for specified durations.

Patient is ≥ 18 years of age
Genetic criteria
- Presence of at least two variant/mutant alleles in the pyruvate kinase liver and red blood cell (PKLR) gene
  documentation required
- At least one of the variant/mutant alleles is a missense variant
  documentation required
Disease severity
- Current hemoglobin level ≤ 10 g/dL≤ 10 g/dL
- Currently receiving red blood cell transfusions regularly, defined as at least six transfusions within the last year≥ 6 transfusions in the last year
Medication is prescribed by or in consultation with a hematologist

Continuation Therapy Criteria

B) Patient Currently Receiving Pyrukynd

Patient is ≥ 18 years of age
Genetic criteria
- Presence of at least two variant/mutant alleles in the pyruvate kinase liver and red blood cell (PKLR) gene
  documentation required
- At least one of the variant/mutant alleles is a missense variant
  documentation required
Clinical benefit per prescriber
- Increase in or maintenance of hemoglobin levels
- Improvement in or maintenance of hemolysis laboratory parameters (examples: indirect bilirubin, lactate dehydrogenase, haptoglobin)
- Decrease in or maintenance of transfusion requirements
Medication is prescribed by or in consultation with a hematologist

Recommended Monitoring / Discontinuation

Operational guidance referenced from prescribing information

Recommended Monitoring / Discontinuation: Discontinue Pyrukynd if no benefit has been observed by 24 weeks as evaluated by hemoglobin and hemolysis laboratory results and transfusion requirements24 weeks

Trial duration to assess benefit24 weeks — discontinue Pyrukynd if no benefit observed by 24 weeks as evaluated by hemoglobin, hemolysis labs, and transfusion requirements.

Not Covered / Experimental Uses

Pyrukynd is considered experimental/investigational/unproven for uses not listed above, including:

Patients homozygous for the c.1436G>A (p.R479H) variant/mutation in the PKLR gene
Patients with two non-missense variants/mutations (without presence of another missense variant/mutation) in the PKLR gene

Denial Risk

Not covered: specific genotypes

Claims for patients who are homozygous for the c.1436G>A (p.R479H) PKLR variant or who have two non-missense PKLR variants without a missense variant are considered experimental/investigational and are not covered. Do not approve coverage for these specific genotypes.

Provider Actions & Documentation Requirements

Prior Authorization

Prior authorization required

Prior authorization is required for Pyrukynd. Approvals are provided for 6 months for initial therapy and 1 year for continuing therapy when criteria are met. When durations are expressed in months, 1 month = 30 days.

Documentation Required

Documentation of genetic testing required

Provide documentation of genetic testing that shows the presence of at least two PKLR gene variant/mutant alleles and that at least one of the variants is a missense variant (for example, a genetic test report).

Documentation Required

Documentation of clinical benefit for continuing therapy

For patients currently receiving Pyrukynd, prescribers must document clinical benefit to continue therapy. Acceptable evidence includes increase in or maintenance of hemoglobin levels; improvement in or maintenance of hemolysis laboratory parameters (examples: indirect bilirubin, lactate dehydrogenase, haptoglobin); or decrease in or maintenance of transfusion requirements.

Documentation Required

Specialist prescriber requirement

Pyrukynd must be prescribed by or in consultation with a hematologist; approval requires involvement of a physician who specializes in the condition being treated.

Background

Pyrukynd is a pyruvate kinase activator indicated for treatment of hemolytic anemia due to pyruvate kinase deficiency in adults. Pyruvate kinase deficiency is a rare autosomal recessive disorder caused by mutations in the PKLR gene that reduce pyruvate kinase activity in red blood cells and lead to hemolytic anemia of variable severity with complications such as iron overload, bilirubin gallstones, pulmonary hypertension, thrombosis, and extramedullary hematopoiesis.

Regular red blood cell transfusions: defined as at least six transfusions within the last year and used as a disease-severity criterion for eligibility.

Missense variant: a genetic variant that results in a single amino acid change in the encoded protein; the policy requires that at least one PKLR allele be a missense variant for coverage eligibility.

Revision History

02/19/2025Annual RevisionLatest

Annual Revision, Summary of Changes = No criteria changes (02/19/2025).

02/28/2024Annual Revision

02/28/2024 revision removed requirement that patients currently receiving therapy have current hemoglobin ≤ 12 g/dL (historical).

Policy Summary

PayerCigna

PolicyPyrukynd (mitapivat) prior authorization for pyruvate kinase deficiency

Policy CodePolicy N/A

Change TypeAnnual revision (no criteria changes)

Effective Date

Next Review Date

Key ActionPrior authorization is required; provide genetic testing documentation showing at least two PKLR variants with at least one missense variant and document clinical benefit for continuation.

On This Page

OpenPayer

Pyrukynd (mitapivat) prior authorization for pyruvate kinase deficiency

Coverage Summary

Initial Therapy Criteria

Continuation Therapy Criteria

Recommended Monitoring / Discontinuation

Not Covered / Experimental Uses

Provider Actions & Documentation Requirements

Applicable Codes

Clinical Evidence & References

Background

Revision History