Sepiapterin: First Approval

An oral formulation of sepiapterin (Sephience™) is being developed by PTC Therapeutics for the treatment of phenylketonuria (PKU). Sepiapterin is a natural precursor of enzyme cofactor tetrahydrobiopterin (BH₄), which is required for phenylalanine hydroxylase (PAH)-mediated phenylalanine metabolism. Sepiapterin enhances PAH activity, which is deficient in patients with PKU. Sepiapterin received its first approval on 19 June 2025 in the European Union, for use in hyperphenylalaninaemia (HPA) in adult and paediatric patients with PKU. This was followed by approval in the USA on 28 July 2025, for the treatment of HPA in adult and paediatric patients ≥ 1 month of age with sepiapterin-responsive PKU. This article summarizes the milestones in the development of sepiapterin leading to its first approval for HPA in adult and paediatric patients with PKU.