Sephience™ (sepiapterin) has recently received approval from the U.S. Food and Drug Administration (FDA) for the treatment of phenylketonuria (PKU) in both children and adults. Phenylketonuria (PKU) is a rare inherited metabolic disorder characterized by the inability to metabolize phenylalanine (Phe), an essential amino acid found in most protein-rich foods.
PKU is caused by a genetic defect affecting the production of the phenylalanine hydroxylase (PAH) enzyme, which is necessary for the appropriate metabolism of Phe. If left untreated or inadequately managed, Phe can build up to toxic levels, leading to irreversible neurological damage such as intellectual disability, seizures, developmental delays, memory problems, and emotional or behavioral problems.
While neonates with PKU are usually asymptomatic, the importance of an early diagnosis through newborn screening programs cannot be overemphasized, as any harm caused by raised Phe levels in the first few years of life will be permanent.
It is estimated that around 58,000 people across all geographical locations are impacted by PKU. The newly approved drug Sephience has demonstrated efficacy in treating hyperphenylalaninemia (HPA) in patients above 1 month of age with a response to sepiapterin. Sephience offered a new treatment option with broad labeling.
Sephience acts as a natural precursor to tetrahydrobiopterin (BH4), which is a critical cofactor for the enzyme PAH. By working on enhancing the function of this enzyme, Sephience decreases elevated blood Phe levels in appropriately responding patients.
The FDA approval was largely based on strong evidence from the Phase 3 APHENITY clinical trial that supported both the safety and efficacy of Sephience and the longer-term benefits shown in the long-term extension study.
The approval is considered a major milestone for health care providers and patient advocacy organizations. Dr. Matthew B. Klein, PTC Therapeutics CEO, stated, “This FDA approval meets an important unmet medical need”. He continued to say that “PTC Therapeutics’ expertise in rare disease therapeutics will ensure Sephience is the future standard of care for PKU.” Dr. Klein continued to add that PTC’s field teams are ready to ensure eligible patients across the U.S. quickly receive access to Sephience.
Catherine Warren, the Executive Director of the National PKU Alliance, stated that this decision is a major step forward for the PKU community and its dreams. Warren added how the treatment has the potential to significantly impact the quality of life for patients across all ages and PKU subtypes that could benefit from treatment.
Sephience has received marketing approval in the European Economic Area and is currently undergoing regulatory reviews in other major markets, including Japan and Brazil, in addition to its FDA approval. This global recognition for Sephience indicates a shift toward a greater awareness of the need for better therapies for PKU.
Sephience signifies an important therapeutic advance for the PKU community. Its approval provides a new way to effectively manage HPA in patients with sepiapterin-responsive PKU, potentially improving long-term outcomes and quality of life for individuals affected by this lifelong disorder.
References: PTC Therapeutics. PTC Therapeutics Announces FDA Approval of Sephience™ (sepiapterin) for the Treatment of Children and Adults Living with Phenylketonuria (PKU). Published July 28, 2025. Accessed July 31, 2025. PTC Therapeutics Announces FDA Approval of Sephience™ (sepiapterin) for the Treatment of Children and Adults Living with Phenylketonuria (PKU) | PTC Therapeutics, Inc.
