FDA Grants Fast Track Designation to BioMarin for PKU Gene Therapy

Rare Daily Staff

The U.S. Food and Drug Administration granted BioMarin Pharmaceutical Fast Track designation for its experimental gene therapy BMN 307 to treat the metabolic disorder PKU.

PKU is a rare genetic disease that manifests at birth and is marked by an inability to break down phenylalanine (Phe), an amino acid that is commonly found in many foods. Left untreated, high levels of Phe become toxic to the brain and may lead to serious neurological and neuropsychological issues, affect a person’s ability to think and problem solve, and can lead to depression, anxiety, and behavior disturbance impacting quality of life. Due to the seriousness of these symptoms, in many countries, infants are screened at birth to ensure early diagnosis and treatment to avoid intellectual disability and other complications. According to treatment guidelines, PKU patients should maintain lifelong control of their Phe levels.

BMN 307 is an AAV5-phenylalanine hydroxylase (PAH) gene therapy designed to normalize blood phenylalanine (Phe) concentration levels in patients with PKU by inserting a correct copy of the PAH gene into liver cells. BMN 307 will be evaluated to determine safety and whether a single dose of treatment can restore natural Phe metabolism, increase plasma Phe levels, and enable a normalization of diet in patients with PKU.

BMN 307 is a potential third PKU treatment option in BioMarin’s PKU franchise and a second gene therapy development program.

BioMarin’s clinical program is composed of two key studies. Phearless, a phase 1/2 study, will evaluate the safety, efficacy, and tolerability of a single intravenous administration of BMN 307 in patients with PKU.  The study consists of a dose-escalation phase, followed by a cohort expansion phase once an initial efficacious dose has been demonstrated.  In addition, BioMarin is sponsoring an observational study, Phenom, which includes patients with PKU to measure both established and new markers of disease and clinical outcomes over time.

Fast Track designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fulfill an unmet medical need, enabling drugs to reach patients earlier. Clinical programs with Fast Track designation may benefit from early and frequent communication with the FDA throughout the regulatory review process.

These clinical programs may also be eligible to apply for Accelerated Approval and Priority Review if relevant criteria are met, as well as Rolling Review, which means that completed sections of the Biologic License Application can be submitted for review before the entire FDA application is complete.  Both the FDA and European Medicines Agency have granted BMN 307 Orphan Drug Designation.

“Fast Track designation combined with our ability to conduct our clinical studies incorporating material manufactured using a commercial-ready process will further facilitate rapid clinical development of BMN 307 gene therapy,” said Hank Fuchs, president of worldwide research and development at BioMarin.  “

Photo: Hank Fuchs, president of worldwide research and development at BioMarin