Results From the PEGASUS Clinical Trial of Pegvaliase in Patients With PKU

Kevin Eggan, PhD, Chief Scientific Officer at BioMarin, discusses new results from the PEGASUS clinical trial of Palynziq (pegvaliase) for treating patients with phenylketonuria (PKU). PKU is a genetic metabolic disorder that increases the body's levels of phenylalanine. Phenylalanine is an amino acid of proteins. Humans cannot make phenyalanine, but it is a natural part of the foods we eat. However, people do not need all the phenyalanine they eat, so the body converts extra phenylalanine to another harmless amino acid, tyrosine. People with PKU cannot properly break down the extra phenylalanine to convert it to tyrosine. This means phenylalanine builds up in the person's blood, urine, and body. Without treatment, children with classic PKU develop permanent intellectual disability. Light skin and hair, seizures, developmental delays, behavioral problems, and psychiatric disorders are also common. In most cases, PKU is caused by genetic changes in the PAH gene. The phase 3 PEGASUS clinical trial was a multicenter, open-label, randomized, controlled study evaluating the safety and efficacy of pegvaliase compared to diet alone in 55 patients ages 12 to 17 years with PKU. Pegvaliase is a substitute for the deficient PAH enzyme in PKU that contains a PEGylated version of phenylalanine ammonia lyase to break down blood phenylalanine (Phe). It is currently approved for the treatment of adults with PKU. New data from the study was recently presented at the 15th International Congress of Inborn Errors of Metabolism. The primary endpoints of the study are change in blood Phe concentration and characterization of the safety profile in adolescents. Secondary endpoints include change in total dietary protein intake and pharmacokinetics. The study consists of two parts: a primary treatment phase lasting 72 weeks and an extension phase lasting for an additional 80 weeks of monitoring. Results from the study show the ability of pegvaliase to significantly lower Phe compared to diet alone. At baseline, mean blood Phe was 1026.4 µmol/L and 49.1% of participants had blood Phe levels above 1000 µmol/L. After the 72 week primary treatment phase, 45.2% of participants in the pegvaliase group achieved reductions in blood Phe concentrations of 50% or more from baseline, with many reaching guideline-recommended and normal Phe target levels. Additionally, the safety profile and overall efficacy in adolescents were consistent with the known profile of pegvaliase in adults. The majority of adverse events were manageable and only 5.6% were considered serious and led to study discontinuation. Chapters: Introduction 00:00 PKU Overview 00:39 Current Management 1:31 PEGASUS Clinical Trial 3:21 Takeaway Message 5:05