PKU is a rare genetic disease that manifests at birth and is marked by an inability to break down the amino acid phenylalanine (Phe). Left untreated, PKU may lead to serious neurological and neuropsychological issues that affect a person's ability to think and problem-solve and can lead to depression, anxiety, and behavior disturbances.

Recently the firm dosed its first participant in the global Phearless phase I/II study with BMN 307, an adeno-associated virus serotype 5 (AAV5)-phenylalanine hydroxylase (PAH) gene therapy drug designed to normalize blood Phe concentration levels. The drug will be evaluated to determine its safety and also whether a single dose can restore natural Phe metabolism, increase plasma Phe levels, and allow for a normal diet.

The Phearless study consists of a dose-escalation phase, followed by a cohort expansion phase once an initially efficacious dose has been demonstrated. The firm is also conducting an observational study (Phenom) that includes patients with PKU to measure both established and new markers of disease and clinical outcomes.

BioMarin is conducting Phearless with material manufactured in a commercial-ready process to facilitate rapid clinical development and potentially support approval. It has a vector production facility in Novato, CA, that produces both valoctocogene roxaparvovec and BMN 307 investigational gene therapies.

BMN 307 is a potential third PKU treatment option and BioMarin's second gene therapy drug. In addition to the fast track designation, the FDA and European Medicines Agency have granted BMN 307 orphan drug designation.