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

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: During Part 1, the participants took sepiapterin for 2 weeks to find out whether it decreased their Phe levels. -Participants whose blood Phe levels decreased by at least 20% were classed as responsive to sepiapterin and could continue to Part 2. -Participants whose blood Phe levels decreased by less than 20% did not continue to Part 2. During Part 2: -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?: NCT05099640.