BioMarin files BLA at FDA for pegvaliase, a PEGylated recombinant phenylalanine ammonia lyase enzyme product, to reduce blood phenylalanine (Phe) levels in adult patients with phenylketonuria.

BioMarin Pharmaceutical Inc. announced that the company submitted a Biologics License Application (BLA) on 30 June 2017 to the FDA for pegvaliase, a PEGylated recombinant phenylalanine ammonia lyase enzyme product, to reduce blood phenylalanine (Phe) levels in adult patients with PKU (Phenylketonuria) 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.

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. "Not all PKU patients experience the same symptoms, but we know that these symptoms improve with a reduction in blood Phe levels," said Nicola Longo, M.D., Ph.D., Professor at the University of Utah School of Medicine and investigator for the pegvaliase Phase III studies. "For those adult patients who cannot control Phe levels on existing management, pegvaliase can reduce Phe levels and produce meaningful benefits. I look forward to working with the FDA to convey my enthusiasm for a therapy that can improve upon what's currently available."

Comment: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.