BioMarin Receives FDA Fast Track Designation for PKU Investigational Gene Therapy

BioMarin Pharmaceutical announced the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to BMN 307, an investigational gene therapy for the treatment of individuals with PKU.

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, M.D., President, Worldwide Research and Development at BioMarin. "We are looking forward to working closely with the FDA, as well as other health agencies, to evaluate the safety and efficacy of this promising investigational gene therapy as we continue our unwavering 15-year commitment to advance the standard of care for people with PKU."

PKU is a rare genetic disease that manifests at birth and is marked by an inability to break down 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, affecting 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.

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 initially 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.

Gene therapy is a form of treatment designed to address a genetic problem by adding a normal copy of the defective gene. The functional gene is inserted into a vector containing a small DNA sequence that acts as a delivery mechanism, providing the ability to deliver the functional gene to targeted cells. The cells can then use the information from the normal gene to build the functional proteins that the body needs, potentially reducing or eliminating the cause of the disease.

PKU, or phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder affecting approximately 70,000 diagnosed patients in the regions of the world where BioMarin operates and is caused by a deficiency of the enzyme PAH. This enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If the active enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems and psychiatric symptoms. As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU under the age of 40 in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after. PKU can be managed with a severe Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most patients to adhere to the life-long strict diet to the extent needed to achieve adequate control of blood Phe levels. Dietary control of Phe in childhood can prevent major developmental neurological toxicities, but poor control of Phe in adolescence and adulthood is associated with a range of neurocognitive disabilities with significant functional impact.