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Plain Language Summary of Publication
11 November 2026

Efficacy and safety of sepiapterin versus sapropterin in people living with phenylketonuria: a plain language summary of the AMPLIPHY trial

Authors: Maria Giżewska, Laura Guilder, Sarah Gallagher, and Anita InwoodAuthor Info & Affiliations
https://doi.org/10.57264/cer-2026-0115
PDF

Abstract

What is this summary about?

This summary is about a clinical trial called AMPLIPHY. AMPLIPHY was a trial that compared two treatments, sepiapterin and sapropterin, to see how well they worked in children and adults living with phenylketonuria (PKU).
PKU is a rare genetic condition where the body cannot properly break down phenylalanine (Phe), which is an amino acid found in many foods. If people living with PKU are not treated, Phe levels build up in the body, which can affect brain development, thinking skills and behaviour. If left untreated for a long time, this may cause symptoms such as seizures, rashes and problems with movement. A key goal of PKU treatment is to keep blood Phe levels within a target range to avoid these effects.

What happened in the AMPLIPHY trial?

In the AMPLIPHY trial, the researchers wanted to see how well sepiapterin worked in people living with PKU when compared with sapropterin, an alternative treatment for PKU, and to compare the safety of the treatments.
The AMPLIPHY trial had two parts:
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During Part 1, the participants took sepiapterin for 2 weeks to find out whether it decreased their Phe levels.
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Participants whose blood Phe levels decreased by at least 20% were classed as responsive to sepiapterin and could continue to Part 2.
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Participants whose blood Phe levels decreased by less than 20% did not continue to Part 2.
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During Part 2:
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The participants took either sepiapterin or sapropterin for the first 4 weeks followed by 4 weeks of the other treatment.

What were the results?

During Part 1, the researchers found that most people benefited from sepiapterin. Specifically, 82% of participants (67 out of 82) had a reduction in blood Phe levels of at least 20%, and 76% of participants (62 out of 82) had a reduction of at least 30%.
During Part 2, the researchers found that sepiapterin lowered blood Phe levels by 70% more than sapropterin did.
There were no adverse events that were considered serious or that stopped anyone from taking treatment or participating in the trial.

What do the results of the trial mean?

How well did the treatments work: these results showed that sepiapterin lowered blood Phe levels more than sapropterin in children and adults with PKU.
What were the safety findings: sepiapterin was well tolerated, with no unexpected side effects or safety concerns identified.
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.

Acknowledgments

The authors and PTC Therapeutics thank the participants and their families for their involvement in the studies that were included in this summary, as well as the individuals who were involved in the conduct and data collection for these studies.

Financial disclosure

This study and summary were sponsored by PTC Therapeutics.

Competing interests disclosure

M Giżewska: honoraria as a speaker, researcher or for travel support from BioMarin Pharmaceutical, Nutricia and PTC Therapeutics; principal investigator in clinical trials sponsored by Agios Pharmaceuticals, Otsuka Pharmaceutical Development & Commercialization and PTC Therapeutics; participation in advisory boards for Agios Pharmaceuticals, BioMarin Pharmaceutical, Nutricia, PTC Therapeutics and Otsuka Pharmaceutical Development & Commercialization. L Guilder and S Gallagher: nothing to disclose. A Inwood: participation in advisory boards and clinical trial support for PTC Therapeutics. 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

Writing and editorial assistance was provided by Hannah Wedge, MChem, of Oxford PharmaGenesis, and funded by PTC Therapeutics.

Data sharing statement

The original article discussed in this summary is called “Efficacy and safety of sepiapterin versus sapropterin in patients with phenylketonuria: Results from the Phase 3, randomized, crossover, open-label, active-controlled AMPLIPHY trial”.
You can read the original article here: https://doi.org/10.1016/j.metabol.2026.156513.

Open access

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/