FDA approves sepiapterin to treat phenylketonuria in adult, pediatric patients

On July 28, 2025, the FDA approved PTC Therapeutics' sepiapterin (Sephience) to treat adult and pediatric patients with phenylketonuria (PKU), including all age groups and the full spectrum of disease subtypes, according to a press release from PTC. Additionally, the approval includes broad labeling to treat hyperphenylalaninemia (HPA) in adult and pediatric patients 1 month of age and older with sepiapterin-responsive PKU.^1,2

WATCH: Experts react to the FDA approval of sepiapterin to treat PKU

"We are excited to have reached this important milestone for those affected by PKU," said Matthew B. Klein, MD, chief executive officer, PTC, in a press release. "The broad labeling reflects the potential of [sepiapterin] to meet the significant unmet need of PKU patients. The [sepiapterin] clinical data along with our expertise in launching rare disease therapies position [sepiapterin] to become the future standard of care. Our experienced customer facing teams are ready to bring this therapy to children and adults with PKU in the United States as quickly as possible."

“Without treatment, individuals with PKU would have very high blood Phe levels, and high blood Phe levels are a toxin to the brain, so that results in neurocognitive deficits and mood disorders," Suzanne Hollander, MS, RD, LDN, a metabolic dietician at Boston Children’s Hospital previously told Contemporary Pediatrics.³

PKU is typically diagnosed shortly after birth through newborn screening, and treatment begins immediately. The goal is to keep blood Phe levels under 360 micromoles per liter.

In March, PTC announced new data from the phase 3 APHENITY trial, which ultimately led to approval from the FDA.¹ According to the company, key findings included:⁴

• Over 97% of subjects participating in the Phe tolerance protocol of the APHENITY open-label extension study demonstrate the ability to liberalize their diet while on sepiapterin treatment, with a mean increase in protein intake of 126%.
• 66% of subjects participating in the Phe tolerance sub-study reached or exceeded the age-adjusted recommended daily allowance of protein intake for an individual without PKU, while maintaining control of blood Phe levels.
• Genetic variant analysis of subjects participating in the APHENITY study demonstrates that over 70% had a Genotype-Phenotype Value (GPV) consistent with classical PKU.

"From a dietary standpoint, the study was really exciting because we did a Phe tolerance assessment,” said Hollander. “For individuals who had their Phe level lowered with the medication to less than 360, they were able to participate in a portion of the study where we systematically monitored their Phe levels and then increased their dietary or natural protein. Overall, participants saw a 126% increase in natural protein intake and a 50% reduction in their use of medical formula, a meaningful outcome given the burden the formula places on children and families."³

WATCH: PKU and the pediatrician with Suzanne Hollander, MS, RD, LDN

"The approval marks an exciting milestone for the PKU community," said Catherine Warren, executive director, National PKU Alliance in a statement. "This progress brings renewed hope, and we are eager to see the positive impact this new treatment option will have on advancing care and potentially improving quality of life for individuals of all ages and PKU subtypes that respond to this therapy."¹

Sepiapterin is to be used in conjunction with a Phe-restricted diet, with the aim of liberalization to allow for an increase in protein.

"[Sepiapterin and a Phe-restricted diet will go] hand in hand. The approach has always centered around diet, with pharmacologic management as an adjunct to hopefully help liberalize diet," Timothy Tramontana, MD, medical and biochemical geneticist, Cleveland Clinic Foundation, told Contemporary Pediatrics. "That approach has helped a number of people through the use of sapropterin and now with sepiapterin. The hope is to expand the number of patients who may be able to liberalize their diet and increase their protein intake. That is our goal for most of our patients—to help them live a more normal life in terms of intake. It may never be 100% protein unrestricted, but the hope is to liberalize it enough to allow increased intake," said Tramotana.

References:

1. PTC Therapeutics Announces FDA Approval of Sephience™ (sepiapterin) for the Treatment of Children and Adults Living with Phenylketonuria (PKU). PTC Therapeutics. Press release. July 28, 2025. Accessed July 28, 2025. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-approval-sephiencetm-sepiapterin
2. PTC Therapeutics Announces FDA Target Regulatory Action Date for Sepiapterin and Lancet Publication of Phase 3 Trial Results. PTC Therapeutics. Press release. October 14, 2024. Accessed July 25, 2025. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-target-regulatory-action-date
3. Fitch J. PKU and sepiapterin data with Suzanne Hollander, MS, RD, LDN. Contemporary Pediatrics. May 7, 2025. Accessed July 25, 2025. https://www.contemporarypediatrics.com/view/pku-and-sepiapterin-data-with-suzanne-hollander-ms-rd-ldn
4. PTC Therapeutics Presents New Sepiapterin Data from Ongoing Studies. PTC Therapeutics. Press release. March 20, 2025. Accessed July 25, 2025. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-presents-new-sepiapterin-data-ongoing-studies