Rare Disease Report

PKU News: BioMarin Submits Peg-Pal Application to the FDA

JULY 02, 2017
James Radke
BioMarin Pharmaceutical Inc. announced they have submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for pegvaliase to treat patients with Phenylketonuria (PKU). The drug is often referred to as Peg-Pal.
PKU is a rare genetic disorder due to mutations in the PAH gene that leads to reduced levels of the phenylalanine hydroxylase in the body, which in turn causes the accumulation of dietary phenylalanine (Phe) in the blood to potentially toxic levels. Symptoms of high Phe include intellectual disability, behavioral problems, delayed development, seizures, as well as a plethora of other central symptoms.
The mainstay of treatment for these patients is the PKU diet which eliminates all forms of Phe (i.e., all protein). The no protein diet is supplemented by a formula that is fairly expensive and may or may not be covered by insurance. Kuvan (sapropterin) is currently the only orphan drug available for PKU patients. Kuvan helps lower Phe levels in some PKU patients. It is also a BioMarin product.
The new product submitted to the FDA, pegvaliase, is a PEGylated recombinant phenylalanine ammonia lyase enzyme product (i.e., enzyme replacement therapy) to reduce Phe levels. 
Last year, BioMarin announced their pivotal Phase 3 PRISM-2 study involving pegvaliase met its primary endpoint (change in blood Phe compared with placebo). In that study, the pegvaliase treated group maintained mean blood Phe levels at 527.2 umol/L compared to their baseline of 503.9 umol/L. In contrast, the placebo group showed a mean blood Phe levels increased from 536 umol/L at baseline to 1385.7 umol/L by the end of the 8-week study.
Per BioMarin: "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."
"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 3 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."
Earlier this year, we talked to Shawn Christ , PhD, from the University of Missouri about the pathophysiologic changes that occur in the brain of a patient with poorly managed PKU. 

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