The US FDA has granted BioMarin Pharmaceutical Inc. approval for use of pegvaliase-pqpz (PALYNZIQ) for the treatment of phenylketonuria (PKU) in adolescents down to age 12 years.

Pegvaliase-pqpz is the only approved therapy that substitutes the deficient phenylalanine hydroxylase (PAH) enzyme in PKU with a PEGylated version of the enzyme phenylalanine ammonia lyase to break down phenylalanine. The drug was first licensed in the US for adults with phenylketonuria in May 2018.

The indication is now for adults and adolescents who have phenylalanine levels > 600 µmol/L with current management.

The new pediatric approval is based on data from PEGASUS, a phase 3 multicenter open-label randomized controlled study evaluating the safety and efficacy of pegvaliase-pqpz compared to diet alone in adolescents aged 12-17 years with PKU who had phenylalanine levels > 600 µmol/L with current management.

At week 72, reductions in blood phenylalanine were just 19 µmol/L for the 17 patients randomized to diet alone vs 473 µmol/L for the 32 who received the drug, a significant difference. By the end of part 1 of the study, 44% of patients reached levels below guideline recommendations and of those, three quarters achieved levels < 120 µmol/L.

Nine who received pegvaliase-pqpz were able to triple their protein intake from baseline, and to decrease their use of medical food protein by 55%. Six ultimately were able to completely discontinue medical food. 

Adverse reactions occurring in 20% or more of subjects were injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue, and pain in extremity. Most reactions occurred in the induction/titration phase and decreased in frequency during the maintenance phase, according to the company.

Study investigator Stephanie Sacharow, MD, Director, Dr Harvey Levy Program for PKU and Related Conditions, Boston Children’s Hospital, Boston, said in a BioMarin statement, “Adolescence is a period of increasing independence and academic demands, and represents a particularly challenging time for individuals with PKU. The ultra-restrictive diet required for PKU management may become unsustainable, and poor blood phenylalanine control leads to adverse neurocognitive outcomes. PALYNZIQ is the only genotype-independent medication which may bring phenylalanine into the normal range while allowing an unrestricted diet.”

BioMarin is also seeking approval for PALYNZIQ with the European Medicines Agency for adolescents down to 12 years of age.

Sacharow has participated in speaking engagements and served on advisory boards for BioMarin. 

Miriam E. Tucker is a freelance journalist based in the Washington DC area. She is a regular contributor to Medscape Medical News, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.