CurrentCignaPolicy N/A

Metabolic Disorders - Nitisinone Products Prior Authorization Policy

Defines prior authorization requirements, clinical criteria, duration of approval, and non-covered uses for nitisinone products (Harliku, Orfadin, generic nitisinone capsules, Nityr) for hereditary tyrosinemia type 1 and alkaptonuria across Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyMetabolic Disorders - Nitisinone Products Prior Authorization Policy

Policy CodePolicy N/A

Change TypeAgent additions and criteria restructuring

Effective Date

Next Review Date

Key ActionPrior Authorization is required; ensure documentation of diagnostic support and specialist prescribing/consultation as specified.

SourceLink

POLICY UPDATE CHANGES

Harliku was added to the policy.

Alkaptonuria was added as a condition of approval (other uses with supportive evidence).

Criteria were divided based on the specific agent intended for approval (Orfadin/generics and Nityr vs Harliku).

Annual revisions on 11/15/2023 and 11/06/2024 noted as 'No criteria changes.'

2Covered Indications

1 yrApproval Duration

4Named Products

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Coverage stance: covered_with_criteria — nitisinone products (Harliku, Orfadin, generic nitisinone capsules, Nityr) are covered when policy criteria are met. Scope: defines prior authorization requirements, clinical criteria, duration of approval, and non-covered uses for these nitisinone products for hereditary tyrosinemia type 1 and alkaptonuria across Cigna-administered health benefit plans. Approval duration: 1 year. Named products in policy: 4.

Key facts

Covered Indications2

Approval Duration1 year

Named Products in Policy4

Initial Therapy - Hereditary Tyrosinemia Type 1

FDA-Approved Indication: Hereditary Tyrosinemia Type 1 (Approve for 1 year)

Approve for 1 year if the patient meets ALL of the following (A, B, C, and D):

ALL of the following

Diagnosis supported by ONE of the following
- Genetic testing confirms biallelic pathogenic or likely pathogenic variants in the FAH gene
- Patient has elevated levels of succinylacetone in the serum or urine
The medication is prescribed in conjunction with a tyrosine- and phenylalanine-restricted diet
Patient will not be taking the requested agent concurrently with another nitisinone product
Concurrent use of Orfadin, generic nitisinone capsules, Nityr, and Harliku is not allowed
Medication is prescribed by or in consultation with a metabolic disease specialist (or specialist who focuses in the treatment of metabolic diseases)

Initial Therapy - Alkaptonuria (Other Uses with Supportive Evidence)

Other Uses with Supportive Evidence: Alkaptonuria (Approve for 1 year)

Approve for 1 year if the patient meets BOTH of the following (A and B):

ALL of the following

Diagnosis supported by ONE of the following
- Genetic testing confirms biallelic pathogenic or likely pathogenic variants in the homogentisate 1,2 dioxygenase (HGD) gene
- Patient has elevated levels of homogentisic acid (HGA) in the urine
Medication is prescribed by or in consultation with a rheumatologist or metabolic disease specialist (or specialist who focuses in the treatment of metabolic diseases)

Provider Actions & Authorization Requirements

Prior Authorization

Prior authorization required

Prior authorization is required for prescription benefit coverage of nitisinone products. Approvals are provided for the duration noted in the policy (1 year for the listed indications).

Documentation Required

Diagnostic documentation required

Prescriber must document diagnostic support: genetic testing confirming biallelic pathogenic or likely pathogenic variants (FAH for hereditary tyrosinemia type 1; HGD for alkaptonuria) OR biochemical evidence (elevated succinylacetone in serum or urine for tyrosinemia; elevated urinary homogentisic acid (HGA) for alkaptonuria).

Documentation Required

Specialist prescribing/consultation requirement

The medication must be prescribed by or in consultation with an appropriate specialist: a metabolic disease specialist (or specialist who focuses in the treatment of metabolic diseases) for hereditary tyrosinemia type 1; and a rheumatologist or metabolic disease specialist (or specialist who focuses in the treatment of metabolic diseases) for alkaptonuria.

Denial Risk

Concurrent nitisinone therapy prohibited

Claims may be denied or not approved if the patient will take the requested agent concurrently with another nitisinone product. Examples of nitisinone products include Harliku, Orfadin, generic nitisinone capsules, and Nityr; concurrent use of these agents is not allowed.

Documentation Required

Dietary therapy requirement for tyrosinemia

For hereditary tyrosinemia type 1, the prescriber must indicate the medication is prescribed in conjunction with a tyrosine- and phenylalanine-restricted diet.

Clinical Evidence & References

Key references include the prescribing information for Orfadin (2021), Nityr (2024), and Harliku (2025), as well as clinical literature for alkaptonuria including the SONIA trials (SONIA 1 dose-response study; SONIA 2 randomized controlled trial) and reviews of nitisinone in alkaptonuria. The evidence supporting indications comprises manufacturer prescribing information and randomized and open-label clinical trials and supportive reviews.

Background

Background: Nitisinone products are hydroxy-phenylpyruvate dioxygenase (HPPD) inhibitors. Orfadin and Nityr are indicated for treatment of hereditary tyrosinemia type 1 in adults and pediatric patients in combination with dietary restriction of tyrosine and phenylalanine; Harliku is indicated for treatment of alkaptonuria in adults. Diagnosis for these disorders is by genetic testing or biochemical markers: hereditary tyrosinemia type 1 — genetic testing confirming biallelic pathogenic/likely pathogenic variants in the FAH gene or elevated succinylacetone in serum/urine; alkaptonuria — genetic testing confirming biallelic pathogenic variants in the HGD gene or elevated urinary homogentisic acid (HGA).

Concomitant therapy: Concurrent use of more than one nitisinone product (for example, Harliku, Orfadin, generic nitisinone capsules, and/or Nityr) is not allowed per policy and may lead to denial, as there are no data to support concomitant use.

Revision History

07/16/2025material_changeLatest

Harliku was added to the policy and included in examples of nitisinone products; policy criteria were restructured to separate agent-specific approval criteria (Orfadin/generics and Nityr vs Harliku); Alkaptonuria was added as a condition of approval under 'Other Uses with Supportive Evidence' for Harliku.

11/06/2024annual_review

Annual revision noted with no criteria changes.

11/15/2023annual_review

Annual revision noted with no criteria changes.

Policy Summary

PayerCigna

PolicyMetabolic Disorders - Nitisinone Products Prior Authorization Policy

Policy CodePolicy N/A

Change TypeAgent additions and criteria restructuring

Effective Date

Next Review Date

Key ActionPrior Authorization is required; ensure documentation of diagnostic support and specialist prescribing/consultation as specified.

SourceLink

On This Page

OpenPayer

Metabolic Disorders - Nitisinone Products Prior Authorization Policy

Coverage Summary

Initial Therapy - Hereditary Tyrosinemia Type 1

Initial Therapy - Alkaptonuria (Other Uses with Supportive Evidence)

Provider Actions & Authorization Requirements

Applicable Codes

Clinical Evidence & References

Background

Revision History