Pharmacy Prior Authorization Criteria

Sephience (sepiapterin)

For diagnosis of Hyperphenylalaninemia
Indicated for the treatment of hyperphenylalaninemia (HPA) in adult and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU) in conjunction with a phenylalanine (Phe)-restricted diet.

Prior Authorization (Initial Authorization)

Length of Approval: 3 month(s) [B]

AND

AND

Patient will have Phe blood levels measured within 2 weeks of therapy (new starts to therapy only) and periodically for up to 3 months of therapy to determine response [C]

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)

Patient has had an objective response to therapy, defined as a 15% or greater reduction in phenylalanine (Phe) blood levels from baseline

AND

AND

Patient will continue to have blood Phe levels measured periodically during therapy [C]

2025-10-01

Sephience prescribing information. PTC Therapeutics, Inc. Warren, NJ. July 2025.
Muntau AC, Longo N, Ezgu F, et al. Effects of oral sepiapterin on blood Phe concentration in a broad range of patients with phenylketonuria (APHENITY): results of an international, phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2024 Oct 5;404(10460):1333-1345.

All patients who are treating phenylketonuria (PKU) with sepiapterin should also be treated with a phenylalanine (Phe) restricted diet [1].
After initiating treatment at the starting dosage dependent on age, blood Phe levels should be checked to determine response to treatment within 2 weeks. If blood Phe does not decrease, dosage may be titrated incrementally based on blood Phe levels to a maximum daily dosage of 60 mg/kg. Existing dietary protein and Phe intake should not be modified during the evaluation period. Discontinue SEPHIENCE in patients whose blood Phe does not decrease after 2 weeks of treatment at the maximum daily dosage of 60 mg/kg [1]. The 3 month initial authorization duration allows for patients who start on 7.5mg/kg per day to increase their dose to 60mg/kg per day and check blood Phe level response.
Phe blood levels should be checked within 2 weeks of sepiapterin treatment and periodically after that to assess blood Phe control [1].