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Plain Language Summary of Publication
9 December 2025

Sepiapterin as a treatment for people living with phenylketonuria: a plain language summary of the APHENITY trial

Authors: Ania C Muntau, Sarah Gallagher, Melissa Lah, Amaya Belanger-Quintana, and Nicola LongoAuthor Info & Affiliations
Volume 15, Number 1
https://doi.org/10.57264/cer-2025-0116
PDF

Abstract

What is this summary about?

This plain language summary is based on an article about the APHENITY trial that was published in The Lancet journal in October 2024. The APHENITY trial was a phase 3 clinical trial to find out whether sepiapterin helped people living with phenylketonuria (PKU) and to learn more about its safety. PKU is a rare, genetic condition that causes high levels of phenylalanine (Phe) to build up in the body. High levels of Phe in the body can cause symptoms such as seizures, rashes, and problems with movement, and can also affect brain development, thinking skills, and behaviour. These symptoms can have an impact on people's health-related quality of life.

What happened in the APHENITY trial?

Previous studies have shown that sepiapterin is able to decrease Phe levels in the blood. In the APHENITY trial, the researchers wanted to learn more about the efficacy and safety of sepiapterin in a large group of people living with PKU over the course of 8 weeks of treatment. The researchers wanted to:
•
Assess the efficacy of sepiapterin by seeing whether sepiapterin decreased Phe levels in the blood compared with a placebo
•
Assess the safety of sepiapterin by seeing how many health complaints the participants who took sepiapterin had compared with those who took the placebo
The APHENITY trial was carried out in two parts:
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During Part 1, the participants took sepiapterin for 2 weeks to find out if it decreased their Phe levels
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During Part 2, the participants who benefitted from sepiapterin during Part 1 were randomly assigned to either continue taking sepiapterin or start taking a placebo for a further 6 weeks

What were the results?

During Part 1, the researchers found that 114 out of 156 participants benefitted from sepiapterin. This was 73% or about 7 in 10 participants.
During Part 2, the researchers found that the participants who took sepiapterin had reduced blood Phe levels compared with those who took the placebo. The researchers also found that compared with those who took the placebo, more of the participants who took sepiapterin reduced their blood Phe levels to within the ranges recommended by treatment guidelines.
For both parts of the trial, the participants did not have any serious health complaints. So, the researchers concluded that no safety concerns were seen with sepiapterin in this trial.

What do the results of the trial mean?

These results showed that sepiapterin helped to reduce blood Phe levels in the participants, and there were no unexpected safety concerns in people living with PKU.
ClinicalTrials.gov NCT number: NCT05099640
This is an abstract of the Plain Language Summary of Publication article.
To read the full Plain Language Summary of this article, click here to view the PDF.

Author contributions

All authors contributed to the drafting and revision of the manuscript.

Acknowledgments

We thank the participants, their caregivers and families, the investigators, and their teams who took part in this trial.

Financial disclosure

This trial was sponsored by PTC Therapeutics and the summary was funded by PTC Therapeutics.

Competing interests disclosure

AC Muntau declares clinical trial support from BioMarin and PTC Therapeutics; has participated on advisory boards for BioMarin, Jnana Therapeutics, PTC Therapeutics, and Synlogic Therapeutics; and has consulted and lectured for BioMarin, Jnana Therapeutics, and PTC Therapeutics. S Gallagher declares no competing interests. M Lah declares clinical trial support from BioMarin and Homology Medicines; and has participated on advisory boards for BioMarin and PTC Therapeutics. A Belanger-Quintana declares clinical trial support from BioMarin, Moderna, and PTC Therapeutics; has participated on advisory boards for BioMarin, Jnana Therapeutics, Nutricia, and PTC Therapeutics; and has consulted and lectured for BioMarin, Danone, Genzyme/Sanofi, Nestlé, PTC Therapeutics, Recordati Rare Diseases, and Takeda. N Longo declares clinical trial support from BioMarin, Homology Medicines, Jnana Therapeutics, Moderna, and PTC Therapeutics; and has participated on advisory boards for Amgen/Horizon Therapeutics, Amicus Therapeutics, Audentes/Astellas, BioMarin, BridgeBio/CoA Therapeutics, Chiesi/Protalix, Genzyme/Sanofi, Hemoshear, Ipsen, Jaguar Gene Therapy, Jnana Therapeutics, Leadiant Biosciences, Moderna, Nestlé Pharma, PTC Therapeutics, Reneo, and Ultragenyx. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

Medical writing and editorial support were provided by Alexandra Smith, MSc, of PharmaGenesis London, London, UK, and were funded by PTC Therapeutics.

Data sharing statement

The original article discussed in this summary was published in the journal The Lancet and is called “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”. You can read the original article here: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01556-3/abstract
You can read more about this trial here: https://clinicaltrials.gov/study/NCT05099640

Open access

This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
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