PTC Therapeutics Announces Sepiapterin European MAA Validation

PTC Therapeutics, Inc. has announced the validation and acceptance of its Marketing Authorization Application (MAA) for sepiapterin by the European Medicines Agency (EMA) for the treatment of phenylketonuria (PKU). This milestone represents a significant step forward in the availability of sepiapterin for both children and adults with PKU in Europe.

Matthew B. Klein, M.D., CEO of PTC Therapeutics, emphasized the importance of this validation, noting that the European submission is the first of several planned global submissions for 2024. PTC anticipates submitting a New Drug Application (NDA) for sepiapterin to the U.S. Food and Drug Administration (FDA) by the third quarter of 2024. Additionally, the company plans to make submissions in other countries, including Brazil and Japan, within the same year.

The MAA for sepiapterin is supported by data from the phase 3 APHENITY trial. This trial showed a mean reduction of 63% in phenylalanine (Phe) levels among the overall treated population, and a 69% reduction in those with classical PKU. Moreover, 84% of the subjects achieved Phe control as per treatment guidelines, which is less than 360 µmol/L, and 22% of the participants even attained normalization of Phe levels.

The application also incorporates data from an open-label extension study of APHENITY, highlighting the sustained effectiveness of sepiapterin. Furthermore, the Phe tolerance sub-study provided evidence that patients were able to liberalize their diet beyond the recommended daily protein allowance while still maintaining Phe control within the target levels. This ability to ease dietary restrictions while maintaining control over Phe levels is a considerable advantage of sepiapterin for both patients and healthcare providers.

Sepiapterin, previously known as PTC923, is an oral formulation of synthetic sepiapterin. It serves as a precursor to intracellular tetrahydrobiopterin, which plays a crucial role as an enzymatic cofactor in various metabolic processes. Sepiapterin is more bioavailable than exogenously administered synthetic BH4 and holds the potential to treat a broad spectrum of PKU patients.

Phenylketonuria (PKU) is a rare, inherited metabolic disorder that affects brain function. It stems from a genetic defect that impairs the production of the enzyme necessary to break down phenylalanine, an amino acid found in nearly all proteins and many foods. Without proper management, phenylalanine can accumulate to toxic levels in the body, leading to severe and irreversible disabilities, such as intellectual disabilities, seizures, developmental delays, memory loss, and behavioral issues. Early diagnosis typically occurs through newborn screening programs. Globally, around 58,000 individuals are estimated to be living with PKU.

PTC Therapeutics is a global biopharmaceutical company dedicated to discovering, developing, and commercializing medicines for rare disorders. The company prides itself on its innovation and ability to bring transformative therapies to market, aiming to provide treatment options to patients with limited alternatives. PTC’s mission is to maximize value for all stakeholders by leveraging its scientific and clinical expertise and global commercial infrastructure.

In conclusion, PTC's recent progress with sepiapterin marks a significant advancement in the treatment of PKU. By expanding access to this new therapy, PTC hopes to improve the quality of life for individuals affected by this rare metabolic disorder.