BioMarin Pharmaceutical announced the company submitted a Biologics License Application (BLA) on Friday, June 30, 2017 to the U.S. Food and Drug Administration (FDA) for pegvaliase, a PEGylated recombinant phenylalanine ammonia lyase enzyme product, to reduce blood phenylalanine (Phe) levels in adult patients with PKU who have uncontrolled blood Phe levels on existing management. Following receipt of the BLA, the FDA conducts an initial assessment of the application to determine its fileability. The FDA typically notifies the applicant of their filing decision and planned Prescription Drug User Fee Act (PDUFA) action date within 60 to 74 days after receipt of the application. The company also intends to submit an application for registration in the European Union (EU) by year end 2017.
"We believe that pegvaliase offers the promise of an important new treatment option for those adult patients with PKU unable to manage their condition with existing treatments. Pegvaliase has been shown to lower blood Phe levels, which was the primary endpoint for registration of the only therapy currently approved to treat PKU," said Hank Fuchs, M.D., President Worldwide Research and Development. "The current medical guidelines highlight that the primary goal of therapy is to lower Phe, and pegvaliase represents an important advance in achieving that goal for adult PKU patients. We look forward to working with the FDA to bring this treatment to patients."
Pegvaliase is an investigational study drug that substitutes the deficient PAH enzyme in PKU with the PEGylated version of the enzyme phenylalanine lyase, to break down Phe. It is being developed as a potential treatment for adults with inadequately controlled blood Phe levels. In clinical studies, treatment with subcutaneous pegvaliase substantially reduced blood Phe compared to placebo using a randomized withdrawal study design, and led to long-term maintenance of Phe reduction in the majority of adult patients with PKU. Pegvaliase was administered using a dosing regimen that achieved a manageable safety profile, consisting primarily of immune-mediated responses, including anaphylaxis, for which robust risk management measures effective in clinical trials will be proposed.
Phenylketonuria (PKU) or phenylalanine hydroxylase (PAH) deficiency is a genetic disorder affecting approximately 50,000 diagnosed patients in the developed world 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 or PAH deficiency under the age of 40 in developed countries are diagnosed at birth and treatment is implemented soon after. PAH deficiency can be managed with a Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, the strict diet is difficult for most patients to adhere to the extent needed for achieving adequate control of blood Phe levels.