CurrentUnitedHealthcarePolicy 2026 P 2412-2

Nitisinone products (Harliku, Nityr, Orfadin, generic nitisinone)

UnitedHealthcare prior authorization/medical necessity policy for nitisinone products (Harliku™, Nityr®, Orfadin®, and generic nitisinone) governing initial authorization and reauthorization criteria for alkaptonuria (AKU) and hereditary tyrosinemia type 1 (HT-1), prescriber requirements, combination-product restrictions, and authorization duration.

Policy Summary

PayerUnitedHealthcare

PolicyNitisinone products (Harliku, Nityr, Orfadin, generic nitisinone)

Policy CodePolicy 2026 P 2412-2

Change TypeNew program; educational note added

Effective DateMay 1, 2026

Next Review Date

Key ActionPrior authorization is required; approvals issued for 12 months when criteria met.

POLICY UPDATE CHANGES

New program established (2/2026).

Educational note added to AKU reauthorization section (4/2026).

2Covered indications (AKU, HT-1)

12 moAuthorization duration

18+Adult age threshold for AKU

Coverage Summary

UnitedHealthcare’s prior authorization/medical necessity policy covers nitisinone products (Harliku™, Nityr®, Orfadin®, and generic nitisinone) for the treatment of alkaptonuria (AKU) and hereditary tyrosinemia type 1 (HT-1). Initial and reauthorization criteria specify diagnostic, laboratory/genetic, and prescriber requirements. Approvals are issued for 12 months. Prescriptions must be from or in consultation with a metabolic disease specialist (required for HT-1) or a rheumatologist (acceptable for AKU). The requested nitisinone product must not be used in combination with another nitisinone product; combination use will not meet criteria.

Initial Authorization — Harliku or Orfadin for Alkaptonuria (AKU)

Initial Authorization 6 Harliku or Orfadin for Alkaptonuria (AKU)

Approved when ALL of the following are met:

ALL of the following

Diagnosis of alkaptonuria
Patient is ≥ 18 years old
ONE of
- Urinary homogentisic acid (HGA) excretion > 0.4 g/24 hours> 0.4 g/24 hours
  laboratory value
- Biallelic mutation in homogentisate 1,2-dioxygenase (HGD) gene confirmed by genetic testing
  genetic confirmation
The requested drug will not be used in combination with another nitisinone product
no concurrent nitisinone products
Prescribed by or in consultation with a metabolic disease specialist or rheumatologist
prescriber specialty requirement

Reauthorization — Harliku or Orfadin for Alkaptonuria (AKU)

Reauthorization 6 Harliku or Orfadin for Alkaptonuria (AKU)

Approved when ALL of the following are met:

ALL of the following

Documentation of positive clinical response (e.g., reduced urinary homogentisic acid (HGA) levels, improvement in joint symptoms) while on therapy
see definitions/examples
The requested drug will not be used in combination with another nitisinone product
no concurrent nitisinone products
Prescribed by or in consultation with a metabolic disease specialist or rheumatologist
prescriber specialty requirement

Positive clinical response for reauthorization is defined as evidence the patient has benefited from therapy (examples include reduced urinary homogentisic acid (HGA) levels or improvement in joint symptoms) while on treatment; documentation of such response is required for continued approval.

Initial Authorization — Nityr or Orfadin for Hereditary Tyrosinemia Type 1 (HT-1)

Initial Authorization 6 Nityr or Orfadin for Hereditary Tyrosinemia Type 1 (HT-1)

Approved when ALL of the following are met:

ALL of the following

Diagnosis of hereditary tyrosinemia type 1
ONE of
- Elevated levels of succinylacetone (SA) in serum or urine
  laboratory evidence
- Biallelic mutation in fumarylacetoacetate hydrolase (FAH) gene confirmed by genetic testing
  genetic confirmation
Prescribed in conjunction with a tyrosine- and phenylalanine-restricted diet
diet requirement
The requested drug will not be used in combination with another nitisinone product
no concurrent nitisinone products
Prescribed by or in consultation with a metabolic disease specialist
prescriber specialty requirement

Reauthorization — Nityr or Orfadin for Hereditary Tyrosinemia Type 1 (HT-1)

Reauthorization 6 Nityr or Orfadin for Hereditary Tyrosinemia Type 1 (HT-1)

Approved when ALL of the following are met:

ALL of the following

Documentation of positive clinical response (e.g., decrease in urinary/plasma succinylacetone and alpha-1-microglobulin levels) while on therapy
see definitions/examples
The requested drug will not be used in combination with another nitisinone product
no concurrent nitisinone products
Prescribed by or in consultation with a metabolic disease specialist
prescriber specialty requirement

For HT-1 reauthorization, a positive clinical response includes laboratory improvement such as a decrease in urinary or plasma succinylacetone and a decrease in alpha-1-microglobulin while on therapy; documentation of these changes is required for continued approval.

Applicable Codes

Relevant ICD-10 (diagnosis supports automated approvals)ICD-10

No codes listed

Drug identifiers / products referencedNDC|HCPCS|mixed

Harliku	Harliku™ (nitisinone) tablets — indicated for AKU
Orfadin	Orfadin® (nitisinone) capsules and oral suspension — indicated for HT-1 and EMA AKU
Nityr	Nityr® (nitisinone) tablets — indicated for HT-1; typically excluded from coverage per policy note
nitisinone (generic Orfadin)	generic nitisinone capsules

Provider Actions & Prior Authorization Requirements

Prior Authorization

Prior authorization required

Prior authorization is required for nitisinone products. When the policy criteria are met, authorization will be issued for 12 months.

Documentation Required

Submit medical records or lab/genetic confirmation

Providers must submit medical records (e.g., chart notes, laboratory values) demonstrating the required laboratory thresholds or genetic testing results specified in the criteria, such as urinary homogentisic acid (HGA) excretion > 0.4 g/24 hours for AKU or genetic confirmation of biallelic mutations.

Documentation Required

Prescriber specialty requirement

Prescriptions must be from or in consultation with a metabolic disease specialist. For alkaptonuria (AKU) Harliku/Orfadin, a metabolic disease specialist or a rheumatologist is acceptable; for hereditary tyrosinemia type 1 (HT-1), a metabolic disease specialist is required.

Billing Rule

No combination nitisinone products

The requested nitisinone product must not be used in combination with another nitisinone product; combination use will not meet criteria and may result in denial.

Documentation Required

Reauthorization clinical response documentation

For reauthorization, submit documentation of positive clinical response while on therapy. Acceptable evidence examples include reduced urinary HGA levels or improvement in joint symptoms for AKU, and decreased urinary/plasma succinylacetone and alpha-1-microglobulin levels for HT-1.

Background

Background: Nitisinone is a hydroxyphenyl-pyruvate dioxygenase inhibitor. Covered products include Harliku (indicated for reduction of urine homogentisic acid in adult AKU) and Orfadin/generic nitisinone and Nityr (indicated for HT-1). Harliku’s approval was based on pivotal Orfadin studies, with limited additional Harliku-specific clinical trials.

Clinical Evidence & Definitions

Evidence and approvals: the program was approved by the Pharmacy & Therapeutics committee in 2/2026 with a subsequent change control entry in 4/2026 (educational note added to AKU reauthorization). Per the background, Harliku’s FDA approval relied on Orfadin pivotal studies and there were no additional Harliku-specific efficacy trials.

Positive clinical response is defined across indications as signs that the patient is benefiting from therapy: for AKU examples include reduced urinary HGA levels or improved joint symptoms; for HT-1 examples include decreased succinylacetone and decreased alpha-1-microglobulin.

Clinical Thresholds

Laboratory and related thresholds (per criteria)

Urinary HGA excretion> 0.4 g/24 hours

Genetic confirmation (HGD)Biallelic mutation in homogentisate 1,2-dioxygenase (HGD) gene confirmed by genetic testing

Other lab evidence referencedElevated succinylacetone (SA) in serum or urine; increased alpha-1-microglobulin levels noted for HT-1 reauthorization — provided as lab evidence

Prescriber requirement (context)Prescribed by or in consultation with a metabolic disease specialist or rheumatologist

OpenPayer

Nitisinone products (Harliku, Nityr, Orfadin, generic nitisinone)

Coverage Summary

Initial Authorization — Harliku or Orfadin for Alkaptonuria (AKU)

Reauthorization — Harliku or Orfadin for Alkaptonuria (AKU)

Initial Authorization — Nityr or Orfadin for Hereditary Tyrosinemia Type 1 (HT-1)

Reauthorization — Nityr or Orfadin for Hereditary Tyrosinemia Type 1 (HT-1)

Exclusions / Combination Product Restriction

Applicable Codes

Provider Actions & Prior Authorization Requirements

Background

Clinical Evidence & Definitions

Clinical Thresholds

Revision History