Germany will be first launch for PTC's phenylketonuria drug

The European Commission has approved PTC Therapeutics' treatment for the rare disease phenylketonuria (PKU), Sephience, setting up a market debut in Germany next month.

Sephience (sepiapterin) has been given a broad label for the treatment of children and adults with all disease severities of PKU, a genetic disease that manifests at birth and is characterised by an inability to break down phenylalanine (Phe), an amino acid commonly found in many foods.

Left untreated, high levels of the amino acid become toxic to the brain and may lead to serious neurological and neuropsychological issues. Dietary restriction of Phe is the first-line therapy for patients, but that can be hard to manage, and some patients need drug therapies to control Phe levels.

Chief executive Matthew Klein said the EU approval is "a great step in our efforts to bring this safe and highly effective therapy to children and adults affected by PKU worldwide," adding that the broad label "supports that potential for Sephience to address all key PKU patient segments and become the new standard of care."

The EU approval is the first for the drug, although, the FDA in the US is due to deliver its verdict on it by 29th July, and reviews in other countries, including Japan and Brazil, are ongoing. PTC has said it is prioritising the launch of the drug in Germany and other countries where it can achieve early access through named patient programmes.

The approval is based on the results of the phase 3 APHENITY study, which showed that Sephience achieved an impressive 63% reduction in average blood Phe levels. The drug works by boosting BH4, a co-factor for the phenylalanine hydroxylase (PAH) enzyme that is deficient in patients with PKU.

Recent updates to the APHENITY data have shown that 97% of participants in a tolerance study were able to increase their dietary Phe intake, with two-thirds of patients reaching or exceeding the recommended daily allowance of protein intake for an individual without PKU.

Sephience enters a market with one similarly acting competitor on the market, BioMarin's Kuvan (sapropterin dihydrochloride), which in trials was shown to reduce Phe levels by around a third in up to 40% of PKU patients. BioMarin also has another product called Palynziq (pegvaliase) that only works in a minority of patients and can have serious side effects.

The challenge facing PTC with its new drug is that it will be competing not only with Kuvan itself, but also generics of BioMarin's drug, which are now available in several markets, including the US. In its favour is that patients with classical PKU – the most severe form of the disease – showed a 69% reduction in Phe levels. That is a group that doesn't respond to Kuvan.

PTC is confident in the profile of its new product, and Klein said in the company's first-quarter results update that the company is targeting over $1 billion in revenue from the drug, saying it represents "a significant revenue opportunity that will provide the foundation for PTC's future growth."

PTC has estimated that around 58,000 people are living with PKU in world markets where the drug can be reimbursed. Diet liberalisation is considered a critical factor for PKU patients, physicians, and payers and is expected to drive early adoption, according to the company.