Sepiapterin Reduces Phenylalanine Levels in Patients With Phenylketonuria

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The investigational therapy is an oral formulation of synthetic sepiapterin.

Sepiapterin significantly reduced blood phenylalanine levels in adult and pediatric patients with phenylketonuria (PKU), according to results from the APHENITY trial.

The investigational therapy is an oral formulation of synthetic sepiapterin, a precursor to intracellular tetrahydrobiopterin, which is an enzymatic cofactor involved in the metabolism and synthesis of several metabolic products.

In the first part of the phase 3 APHENITY study ( Identifier: NCT05099640), participants received sepiapterin orally once daily for 2 weeks. Those who demonstrated a reduction in phenylalanine levels of 15% or more from baseline were then randomly assigned to receive either sepiapterin or placebo in the second part of the trial.

Ninety-eight patients were included in the primary analysis population (participants who had >30% reduction in phenylalanine levels from baseline during Part 1 of the trial). The primary endpoint was the reduction of blood phenylalanine levels from baseline compared with weeks 5 and 6 in patients from Part 2 of the clinical trial.

Findings showed a mean blood phenylalanine reduction of 63% in patients treated with sepiapterin. Among participants with classical PKU, the mean percent phenylalanine reduction was 69%. Treatment with sepiapterin was found to be significantly beneficial (P <.0001) as there were minimal reductions in phenylalanine levels in patients who received placebo. No serious adverse events were reported during the trial.

“The positive results from the APHENITY trial bring us one step closer to providing a therapy that could deliver meaningful benefit to PKU patients,” said Matthew B. Klein, MD, Chief Executive Officer, PTC Therapeutics. “The Phe reductions observed in the placebo-controlled portion of the study are consistent with, and, in some cases, exceed the magnitude of Phe reductions recorded in the open label portion of the study. We look forward to meeting with regulatory authorities to discuss the path to approval.”


PTC Therapeutics announces APHENITY Trial achieved primary endpoint with sepiapterin in PKU patients. News release. May 17, 2023.