FDA Accepts NDA Filing for PTC Therapeutics' Sepiapterin to Treat Phenylketonuria

PTC Therapeutics, Inc. (NASDAQ: PTCT) has announced that the FDA has accepted its New Drug Application (NDA) for sepiapterin, intended to treat both pediatric and adult patients suffering from phenylketonuria (PKU). The FDA is expected to provide a target action date in the Day 74 Letter under the Prescription Drug User Fee Act (PDUFA).

Matthew B. Klein, M.D., CEO of PTC Therapeutics, emphasized the significance of this milestone, stating that the FDA's acceptance brings the company closer to offering a crucial therapy for individuals with PKU in the United States. Klein highlighted clinical trial data that indicate sepiapterin could significantly benefit PKU patients by allowing diet liberalization, thus addressing a major unmet need in this patient community.

Catherine Warren, Executive Director of the National PKU Alliance (NPKUA), expressed the organization's strong commitment to improving the lives of PKU patients. She noted that families have been eagerly awaiting new treatments to reduce their reliance on restrictive and costly diets. Warren expressed excitement about the FDA's acceptance, viewing it as a major step toward providing another treatment option for PKU patients of all ages.

The NDA submission for sepiapterin draws on highly significant results from the phase 3 APHENITY trial. This trial demonstrated a mean reduction in phenylalanine (Phe) levels by 63% in the overall treated population and by 69% in subjects with classical PKU. The majority of subjects (84%) managed to achieve Phe levels below 360 µmol/L, in line with treatment guidelines, and 22% of participants normalized their Phe levels. Additional data from an open-label extension study of APHENITY supported the durability of sepiapterin's effect. Furthermore, a Phe tolerance sub-study revealed that about 60% of subjects could achieve protein intake above the age-adjusted recommended daily allowance while maintaining Phe levels below 360 µmol/L. These findings suggest that sepiapterin could allow patients to relax their stringent diets while still controlling Phe levels.

Sepiapterin, also known as PTC923, is an oral synthetic formulation designed to increase the activity of the phenylalanine hydroxylase (PAH) enzyme through a dual mechanism. Firstly, sepiapterin acts as a precursor that is quickly absorbed and converted into tetrahydrobiopterin (BH4), a critical cofactor for PAH. Secondly, it acts as a chaperone, preventing PAH misfolding and enhancing enzyme function. This dual action effectively reduces blood phenylalanine levels, offering potential benefits across a wide range of PKU patients.

Phenylketonuria (PKU) is a rare inherited metabolic disorder that affects the brain. It results from a defect in the gene responsible for producing the enzyme needed to break down phenylalanine, an essential amino acid found in proteins and most foods. If untreated or poorly managed, phenylalanine can accumulate to harmful levels, leading to severe and irreversible disabilities such as intellectual disability, seizures, and developmental delays. Symptoms in newborns are generally not apparent but become progressive, with damage from toxic phenylalanine levels in early life being irreversible. PKU is usually diagnosed through newborn screening programs, and approximately 58,000 people worldwide are affected by the condition.

PTC Therapeutics, Inc. is a global biopharmaceutical company dedicated to discovering, developing, and commercializing medicines that provide benefits to people with rare disorders. The company focuses on innovative therapies and has a diversified pipeline aimed at addressing unmet medical needs. PTC strives to maximize value for stakeholders by leveraging its scientific and clinical expertise and global commercial infrastructure.

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