Pegvaliase Approved by FDA for Treatment of PKU

The US Food and Drug Administration (FDA) has granted approval to pegvaliase-pqpz (Palynziq, BioMarin Pharmaceutical) for the treatment of phenylketonuria (PKU), a rare genetic condition, in adults who have uncontrolled blood Phe concentrations >600 micromol/L despite current management strategies.

"The goal in treating PKU is to keep blood Phe levels within the range set in the medical guidelines, as elevation of Phe can be toxic and damaging to the brain,” Cary Harding, MD, a professor at Oregon Health & Science University and the investigator for the Phase 3 studies, said in a statement. “Palynziq provides another much-needed tool for us to help adult patients control their Phe levels, which previously had not been achievable for many adults living with the condition."

The condition impacts an estimated 1 in 12,500 children each year in the United States, and if left untreated, can be toxic to the brain, leading to neurological and neuropsychiatric-related complications that can impact the way a patient thinks, acts, and feels. Infants tend to be screened at birth to ensure early diagnosis and treatment in order to avoid intellectual disability and other complications.

The FDA’s decision was made based on data from a phase 3 clinical trial, PRISM-2, in which pegvaliase reduced blood Phe levels, meeting the primary endpoint of change in blood Phe compared with placebo (P <.0001). In total, 57% of patients were taking medical food at baseline and 16% were on a protein-restricted diet at baseline (defined as receiving greater than 75% of total protein intake from medical food).

During the course of the randomized withdrawal period trial, patients were randomized in a 2:1 ratio to either continued maintenance dosage (20 mg or 40 mg once daily) or to receive matching placebo, for a duration of 8 weeks. Those treated with pegvaliase maintained blood Phe concentrations as compared to randomized withdrawal baseline measurements, while those on placebo returned to their pretreatment concentration levels.

"BioMarin is thrilled to be able to offer this important new therapy to adults with PKU who are unable to control their Phe levels with existing options. The approval of Palynziq is the culmination of more than a decade of perseverance by BioMarin employees dedicated to bringing treatments to PKU adult patients," said Jean-Jacques Bienaimé, the chairman and chief executive officer of BioMarin, said in a statement. "We are proud of this medical achievement and appreciate the FDA's thoughtful review of our application. We also are grateful to the PKU patients and medical communities for their continued partnership and participation in the clinical program that led to the approval of this effective therapy."

According to BioMarin, the therapy is expected to be available in June 2018, with marketing beginning immediately.

The approval is timely as well, coming during National PKU Awareness Month, in which local patient organizations up their continued efforts to spread awareness. Christine Brown, MS, the executive director of the National PKU Alliance, called the therapy a potential game-changer.

"BioMarin has provided unwavering support for the PKU community and continues innovative medical research to advance treatment options for this rare genetic disease," she said.