PTC Therapeutics announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending marketing authorization for Sephience (sepiapterin) for the treatment of phenylketonuria (PKU). Significantly, the recommendation includes a broad label covering patients of all ages and disease severities, positioning the therapy as a potential treatment option for the full spectrum of PKU patients.
"This positive opinion is great news for the PKU patient community in Europe for whom there remains a significant unmet medical need," said Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics. "We look forward to initiating the European launch immediately following the adoption of this positive opinion by the European Commission. The data collected to date continue to support the potential for Sephience to provide a safe and effective treatment that not only lowers phenylalanine levels but also enables diet liberalization even for those with the most severe disease subtypes."
European Launch Strategy
PTC Therapeutics has already begun launch preparations across Europe, with initial focus on Germany and other key European markets where named patient access will be immediately available following approval. The company expects the European Commission to formally ratify the marketing authorization for Sephience within approximately two months. Once approved, the decision will apply to all 27 European Union member states, as well as Iceland, Norway, and Liechtenstein.
The company is simultaneously pursuing regulatory approvals in other major markets. In the United States, the New Drug Application (NDA) for sepiapterin is currently under review by the Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of July 29, 2025. Additional regulatory reviews are ongoing in Japan and Brazil.
Innovative Dual Mechanism of Action
Sephience represents an innovative approach to PKU treatment through its dual mechanism of action. As an oral formulation of synthetic sepiapterin, the drug increases the activity of the phenylalanine hydroxylase (PAH) enzyme in two distinct ways:
-
It functions as a precursor compound that is rapidly absorbed and converted intracellularly to tetrahydrobiopterin (BH4), a critical cofactor of PAH.
-
It provides an independent pharmacological chaperone effect, correcting PAH misfolding to enhance enzyme function.
This dual approach enables Sephience to effectively reduce blood phenylalanine (Phe) levels, potentially benefiting a broad range of PKU patients regardless of disease severity.
Understanding Phenylketonuria
PKU is a rare, inherited metabolic disorder affecting approximately 58,000 people globally. The condition is caused by a genetic defect that impairs the body's ability to produce the enzyme needed to break down phenylalanine (Phe), an essential amino acid found in most protein-containing foods.
When left untreated or poorly managed, Phe can accumulate to toxic levels in the body, causing severe and irreversible neurological damage. Complications include permanent intellectual disability, seizures, delayed development, memory loss, and behavioral and emotional problems. While newborns with PKU typically don't present symptoms initially, the condition is progressive, and damage caused by elevated Phe levels in early life is irreversible.
Most cases of PKU are identified through newborn screening programs, allowing for early intervention. Current management typically involves strict dietary restrictions to limit Phe intake, which can be challenging to maintain and significantly impact quality of life.
Addressing an Unmet Medical Need
The positive CHMP opinion for Sephience represents a potential advancement in PKU management. Current treatment options are limited, with many patients relying primarily on highly restrictive low-protein diets and specialized medical formulas. These dietary restrictions can be difficult to maintain throughout life and often impact patients' quality of life.
Sephience's potential to both lower Phe levels and enable diet liberalization addresses a significant unmet need in PKU care. The broad label recommendation, covering all ages and disease severities, is particularly noteworthy as it would make the therapy available to patients across the full spectrum of PKU, including those with the most severe forms who often have the fewest treatment options.
About PTC Therapeutics
PTC Therapeutics is a global biopharmaceutical company focused on discovering, developing, and commercializing clinically differentiated medicines for patients with rare disorders. The company's portfolio includes multiple approved therapies and a pipeline of investigational treatments targeting rare genetic disorders.
The development of Sephience aligns with PTC's mission to address significant unmet needs in rare disease communities through innovative therapeutic approaches. The company's experience in rare disease drug development and commercialization positions it to potentially bring this new treatment option to PKU patients globally, pending regulatory approvals.
