What Was Approved?
On July 28, 2025, the U.S. Food and Drug Administration approved Sephience (sepiapterin) for the treatment of hyperphenylalaninemia in adults and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria, or PKU.
Sephience must be used together with a phenylalanine-restricted diet.
What Is PKU?
Phenylketonuria is an inherited metabolic disorder in which the body has difficulty breaking down phenylalanine, an amino acid found in protein-containing foods.
If phenylalanine levels remain too high, they can affect the brain and nervous system.
How Does Sephience Work?
Sephience is a phenylalanine hydroxylase, or PAH, activator.
It is intended to improve the body’s ability to process phenylalanine in patients who respond to sepiapterin therapy.
How Is Sephience Taken?
Sephience is an oral powder taken once daily with food.
The starting dose depends on age:
- Younger than 6 months: 7.5 mg/kg daily
- 6 months to under 1 year: 15 mg/kg daily
- 1 year to under 2 years: 30 mg/kg daily
- Age 2 years and older: 60 mg/kg daily
Response is assessed using blood phenylalanine levels.
Does Every Patient With PKU Respond?
No.
The FDA label specifically limits use to sepiapterin-responsive PKU.
Response generally cannot be predicted reliably by genetic testing alone and is determined through a therapeutic evaluation with blood phenylalanine monitoring.
Are Drug Interactions Important?
Yes.
The FDA label recommends avoiding some medicines, including certain:
- Dihydrofolate reductase inhibitors
- Sepiapterin reductase inhibitors
It also includes precautions with levodopa and medicines that affect nitric oxide-mediated vasodilation.
Patients should review all medications and supplements with their healthcare professional.
Bottom Line
Sephience (sepiapterin) is an FDA-approved once-daily oral treatment for adults and children age 1 month and older with sepiapterin-responsive PKU.
It is used together with a phenylalanine-restricted diet, and treatment requires regular monitoring of blood phenylalanine levels.
Sources
- U.S. Food and Drug Administration (FDA) — Drug Trials Snapshot: Sephience.
- U.S. Food and Drug Administration (FDA) — Sephience (sepiapterin) Prescribing Information, July 2025.
- U.S. Food and Drug Administration (FDA) — Novel Drug Approvals for 2025.