The inborn metabolic disorder, Phenylketonuria, is caused by phenylalanin hydroxylase deficiency. The disorder causes elevated phenylalanine in the blood and brain. If left untreated, phenylketonuria can lead to neurotoxicity and development problems.
Today, we are taking a look at the latest regarding phenylketonuria in relation to clinical guidance, FDA approvals, and clinical trials.
Current Guidelines Related to Phenylketonuria
In 2025, the European Society of Phenylketonuria and Allied Disorders released its first update to the 2017 guideline on the diagnosis and treatment of phenylketonuria. The 2025 update included 20 new topics and nearly 90 statements, alongside recommendations, on the pathophysiology, diagnosis, initiation of treatment, and other focuses related to phenylketonuria.
While there isn’t a recent North American-based clinical practice guideline focusing specifically on phenylketonuria, there is a 2024 guideline on phenylalanin hydroxylase deficiency from the American College of Medical Genetics and Genomics (ACMG). The guideline features recommendations regarding diagnosis, management, transition to adulthood, and more.
- Phenylketonuria: Diagnosis and Management
- European Society of Phenylketonuria and Allied Disorders, April 2025
- Phenylalanin Hydroxylase Deficiency Diagnosis and Management
- American College of Medical Genetics and Genomics, December 2024
Recent FDA Approvals for Phenylketonuria
Below are medications recently approved by the U.S. Food and Drug Administration (FDA) that we anticipate being incorporated into future clinical guidelines:
- BioMarin
- Approved: February 2026
- Palynziq received an expanded indication to include pediatric patients 12 years of age and older with phenylketonuria (PKU).
- PTC Therapeutics
- Approved: July 2025
- Sephience was approved for the treatment of children and adults living with phenylketonuria (PKU).
Ongoing Clinical Trials Related to Phenylketonuria
The following are ongoing, Phase 3 clinical trials based in the United States that we anticipate may impact future clinical guidance.
A Long-Term Safety Study of PTC923 in Participants with Phenylketonuria
- PTC Therapeutics
- Anticipated Study Completion: June 2026
A Study to Evaluate the Safety and Efficacy of JNT-517 in Participants With Phenylketonuria (PKU)
- Otsuka Pharmaceutical Development & Commercialization, Inc.
- Anticipated Study Completion: March 2028
A Study of Sepiapterin in Participants with Phenylketonuria (PKU)(EPIPHENY)
- PTC Therapeutics
- Anticipated Study Completion: February 2031
Sign up for alerts to keep up with the latest guidelines and insights.