Nicola Longo, MD, PhD, Professor and Chief of Division of Clinical Genetics at the University of California, Los Angeles, discusses data presented at the 2025 ACMG Annual Clinical Genetics Meeting highlighting the benefits of sepiapterin in patients with classical phenylketonuria (PKU).
PKU is a rare, genetic, metabolic disorder due to mutations in the enzyme phenylalanine hydroxulase (PAH). This results in phenylalanine (Phe) build up in the body. Without treatment, children with classic PKU develop permanent intellectual disability. Light skin and hair, seizures, developmental delays, behavioral problems, and psychiatric disorders are also common symptoms. In most cases, PKU is caused by mutations in the PAH gene.
Sepiapterin is a precursor compound that is rapidly absorbed and converted into tetrahydrobiopterin that increases activity of PAH. The treatment also has the ability to target and correct misfolding of PAH, reducing blood phenylalanine levels.
In new data presented at the 2025 ACMG Annual Clinical Genetics Meeting, sepiapterin showed meaningful benefit in the treatment of patients with PKU. The data comes from the phase 3 APHENITY clinical trial and open-label extension. Over 70% of participants demonstrated phenotypes associated with classical PKU.
In the study, over 97% of participants demonstrated the ability to liberalize their diet, with a mean increase in protein intake of 126% while being treated with sepiapterin. Further, 66% of participants reached or exceeded the age-adjusted recommended daily allowance of protein intake for individuals without PKU. These patients were also able to maintain control of blood Phe levels.
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To learn more about PKU and other rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/