CurrentUnitedHealthcarePolicy N/A

Sephience (sepiapterin) prior authorization

Defines prior authorization criteria for Sephience (sepiapterin) for treatment of sepiapterin-responsive phenylketonuria (PKU) in members covered by UnitedHealthcare; applies to pharmacy prior authorization programs.

Policy Summary

PayerUnitedHealthcare

PolicySephience (sepiapterin) prior authorization

Policy CodePolicy N/A

Change TypeNew prior authorization program

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization; approvals (initial and reauthorization) are issued for 12 months when criteria are met.

SourceLink

POLICY UPDATE CHANGES

New prior authorization program established for Sephience (sepiapterin).

12 monthsauthorization duration

>=1minimum age (mo)

3initial criteria count

3reauthorization criteria count

Coverage Criteria for Sephience (sepiapterin)

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Initial Authorization

Criterion A: Diagnosis of phenylketonuria (PKU)
Criterion B: Patient is actively on a phenylalanine-restricted diet
Criterion C: Patient is not receiving Sephience in combination with sapropterin dihydrochloride or Palynziq (pegvaliase-pqpz)

Authorization note: Authorization issued for 12 months

inv-02: COVERAGE CRITERIA

Covered when ALL of the following are met for reauthorization

Reauthorization

Criterion A: Patient is actively on a phenylalanine-restricted diet
Criterion B: Blood phenylalanine (Phe) levels continue to remain lower than baseline level
Criterion C: Patient is not receiving Sephience in combination with sapropterin dihydrochloride or Palynziq (pegvaliase-pqpz)

Authorization note: Authorization issued for 12 months

Use of Sephience (sepiapterin) in combination with sapropterin dihydrochloride or Palynziq (pegvaliase-pqpz) is expressly excluded. Requests for Sephience that propose concurrent therapy with either sapropterin dihydrochloride or pegvaliase-pqpz do not meet the coverage criteria and are not eligible for authorization.

Initial Therapy Criteria

inv-11: INITIAL THERAPY CRITERIA

Initial authorization requirements

Initial

Diagnosis of phenylketonuria (PKU)
Diet: Patient is actively on a phenylalanine-restricted diet
No combination: Patient is not receiving Sephience in combination with sapropterin dihydrochloride or Palynziq (pegvaliase-pqpz)

Authorization note: Authorization issued for 12 months

Continuation / Reauthorization Criteria

inv-12: CONTINUATION CRITERIA

Reauthorization requirements

Reauthorization

Diet: Patient is actively on a phenylalanine-restricted diet
Phe response: Blood Phe levels continue to remain lower than baseline level
No combination therapy: Patient is not receiving Sephience in combination with sapropterin dihydrochloride or Palynziq (pegvaliase-pqpz)

Authorization note: Authorization issued for 12 months

Provider Actions and Operational Rules

Prior Authorization

Prior Authorization Required

Prior authorization is required for initial and reauthorization requests. When criteria are met, approvals are issued for 12 months.

Authorization duration: 12 months
Applies to initial and reauthorization requests

Denial Risk

Triggers for Denial

Requests may be denied if the patient does not have a diagnosis of phenylketonuria (PKU), the patient is not actively on a phenylalanine-restricted diet, or clinical documentation does not demonstrate blood phenylalanine (Phe) levels remain below baseline for reauthorization.

Denial triggers: Absence of PKU diagnosis (ICD-10)
Denial triggers: Patient not on a phenylalanine-restricted diet
Denial triggers: Lack of evidence of continued Phe reduction from baseline for reauthorization

Note

Concurrent Therapy Prohibition

Not specified beyond prohibition of concurrent use with sapropterin dihydrochloride (Kuvan) or Palynziq (pegvaliase-pqpz).

Concurrent use prohibited with sapropterin dihydrochloride
Concurrent use prohibited with Palynziq (pegvaliase-pqpz)

Documentation Required

Operational Considerations

UnitedHealthcare may approve initial and reauthorization requests based solely on previous claim or medication history, diagnosis codes (ICD-10), and/or claim logic. Use of automated approval and re-approval processes varies by program and therapeutic class. Medical necessity determinations and supply limits may also apply.

Operational approvals may rely on claim history, medication fills, and ICD-10 diagnosis codes
Automated approval/re-approval processes vary by program
Medical necessity and supply limits may be enforced

Step	Requirement
1
Concurrent use with sapropterin dihydrochloride or Palynziq (pegvaliase-pqpz) is disallowed; no other step therapy is specified.

Definitions

Sephience (sepiapterin) — definition

Generic namesepiapterin

Brand nameSephience

Drug classPhenylalanine hydroxylase (PAH) activator

Indication (covered)Sepiapterin-responsive phenylketonuria (PKU) with hyperphenylalaninemia in patients 1 month of age and older

Use withTo be used in conjunction with a phenylalanine-restricted (Phe-restricted) diet

Phe-restricted diet — definition and role

DefinitionPhenylalanine-restricted (Phe-restricted) diet: dietary management required to be used in conjunction with Sephience therapy

Role in therapyPart of core treatment regimen for sepiapterin-responsive PKU when prescribing Sephience

Patient populationApplies to patients 1 month of age and older receiving Sephience

Background

Sephience (sepiapterin) is a phenylalanine hydroxylase (PAH) activator indicated for treatment of hyperphenylalaninemia in patients with sepiapterin-responsive phenylketonuria (PKU) aged 1 month and older. It is intended to be used in conjunction with a phenylalanine-restricted diet.

Prior authorization is required for Sephience; when the coverage criteria are met, initial and reauthorization approvals are issued for 12 months. Clinical review may consider diagnosis, diet adherence, and blood phenylalanine (Phe) response when evaluating medical necessity.

UnitedHealthcare may also use prior claims/medication history, diagnosis codes (ICD-10), and claim logic to determine approval. State mandates and member-specific benefit plan provisions may apply.

Policy Summary

PayerUnitedHealthcare

PolicySephience (sepiapterin) prior authorization

Policy CodePolicy N/A

Change TypeNew prior authorization program

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization; approvals (initial and reauthorization) are issued for 12 months when criteria are met.

SourceLink

On This Page

OpenPayer

Sephience (sepiapterin) prior authorization

Coverage Criteria for Sephience (sepiapterin)

Initial Therapy Criteria

Continuation / Reauthorization Criteria

Provider Actions and Operational Rules

Step Therapy / Concomitant Therapy Rules

Definitions

Background