Matthew Klein, MD, MS, FACS, Chief Development Officer at PTC Therapeutics, discusses PTC-923, an investigational cofactor therapy for phenylketonuria (PKU).
PKU is a rare genetic metabolic disorder that results in reduced activity of phenylalanine hydroxylase that leads to an accumulation of phenylalanine in the body, which can cause significant organ damage, especially in the central nervous system. If left untreated, PKU patients can develop chronic intellectual, neurodevelopmental, and psychiatric disabilities, as well as seizures and heart problems. Lifelong restriction of phenylalanine intake through the diet is needed to prevent buildup of phenylalanine in the body. However, this diet is particularly difficult to adhere to.
PTC923 is an oral formulation of synthetic sepiapterin, a precursor to intracellular tetrahydrobiopterin, which is an enzymatic cofactor involved in the metabolism and synthesis of numerous metabolic products, including phenylalanine. As Dr. Klein explains, PTC923 has been tested in phase 1 and phase 2 trials where, in the latter, it demonstrated efficacious over sapropterin dihydrochloride (Kuvan), the standard targeted therapy for PKU. In this phase 2 trial, even patients with a severe lack of phenylalanine hydroxylase had significantly decreased levels of phenylalanine when taking PTC923 compared to sapropterin dihydrochloride.
PTC Therapeutics expects to initiate the global, placebo-controlled phase 3 APHENITY trial in mid-2021 to evaluate PTC923 in patients with PKU. Results are expected late-2022.
To learn more about PKU and other rare metabolic disorders, visit checkrare.com/diseases/metabolic-disorders/