BioMarin Submits CTA in UK for Investigational Gene Therapy for PKU

BioMarin Pharmaceutical has submitted a Clinical Trial Application (CTA) with the Medicines and Healthcare Products Regulatory Agency (MHRA) in the U.K. for BMN 307, an investigational AAV5-phenylalanine hydroxylase (PAH) gene therapy designed to reduce blood phenylalanine (Phe) concentrations levels in patients with PKU. BMN 307 will be evaluated to determine whether a single dose of treatment can restore Phe metabolism in patients with PKU, normalize plasma Phe level, and enable a normal diet. The company expects to start enrolling patients in a Phase 1/2 trial early next year and is actively preparing regulatory submissions for other countries. BMN 307 represents a potential third PKU treatment option in BioMarin's PKU franchise and its second gene therapy development program. BMN 307 follows BioMarin's first investigational gene therapy program, valoctocogene roxaparvovec for severe hemophilia A, currently in a Phase 3 study.

"This clinical trial application marks the latest milestone in BioMarin's 15-plus year commitment to the PKU community. BioMarin has brought the only two approved therapies for PKU to patients around the world," said Hank Fuchs, President, Worldwide Research and Development at BioMarin. "Leveraging our expertise in gene therapy, we are pleased to be adding a new gene therapy product, which is potentially a transformative solution, to build on our current achievements for the PKU community."

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 found in most forms of protein. Left untreated, high levels of Phe become toxic to the brain and may lead to serious neurological and neuropsychiatric-related issues, affecting the way a person thinks, feels, and acts. 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.

The Phase 1/2 study will evaluate the safety efficacy and tolerability of a single intravenous administration of BMN 307 in patients with PKU. The Phase 1/2 study consists of a dose-escalation phase, followed by a dose expansion phase. In addition, there is also an observational study in PKU patients to measure markers of disease and clinical outcomes over time in patients.

Gene therapy is a form of treatment designed to address a genetic problem by adding a corrected 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 cells. The cells can then use the information to build the functional proteins that the body needs, potentially reducing or eliminating the cause of the disease.

PKU, or PAH deficiency, is a genetic disorder affecting approximately 50,000 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 Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most adult patients to adhere to the strict diet to the extent needed for achieving adequate control of blood Phe levels.

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