Sapropterin Dihydrochloride

PTC Therapeutics’ daily pill has succeeded in its bid to secure US approval for a rare metabolic disorder, one month after securing the green light in Europe. The FDA approved sepiapterin on Monday for adults and children aged 1 month or older with phenylketonuria (PKU). The drug will be marketed as Sephience. PKU is caused by a defect in the gene that encodes an enzyme responsible for breaking down the amino acid phenylalanine. The amino acid builds up in the body, causing serious disabilities, delayed development and seizures, among other symptoms. Sepiapterin is a precursor to a chemical called tetrahydrobiopterin or BH4, which plays a key role in helping the phenylalanine hydroxylase enzyme function properly. The drug also corrects the misfolding of the enzyme in what PTC describes as a “chaperone effect.” Sephience will have a wholesale acquisition cost of $41,000 per month (or around $492,000 per year), based on an average patient weight of 45 kg. The price tag is “considerably higher” than Leerink analysts had expected, according to a Monday note. PTC’s share price $PTCT was up 9% at market open Tuesday. Sephience was approved by the EMA in June and has been launched in Europe. PTC should be ready to launch Sephience “right away” in the US, CEO Matthew Klein told Endpoints News in an interview ahead of the decision. The company’s commercial team has already scoped out PKU centers of excellence, launched disease education and awareness campaigns, and started speaking with payers, he added. There are around 58,000 people with PKU worldwide, according to PTC. Last week, Leerink analysts estimated that Sephience will reach peak sales of $725 million. In the US, they expect about 1,800 patients will take the drug at its peak. Patients often have to manage their symptoms by following a highly restrictive low-protein diet. There are two approved treatments for the disease, both of which were developed by BioMarin. Kuvan, a form of the BH4 cofactor, was greenlit in the US in 2007. But the drug has limited bioavailability because the cofactor isn’t easily absorbed in the gastrointestinal tract, Klein said. BioMarin’s enzyme replacement therapy Palynziq secured FDA approval for adults with PKU in 2018, though it carries a black box warning for anaphylaxis. PTC’s filing was based on data from the Phase 3 APHENITY trial in 157 patients with PKU. For the study’s primary endpoint, sepiapterin achieved a mean 63% reduction in phenylalanine levels averaged across weeks five and six. More than 80% of patients reached phenylalanine control, defined as levels of less than 360 µmol/L. PTC then shared results from an open-label extension in March, which showed more than 97% of patients included in a phenylalanine tolerance protocol were able to liberalize their diet , with an average 126% increase in protein intake. Editor’s note: The company’s share price was updated.