FDA Approves Pegvaliase-pqpz to Treat Adults With Phenylketonuria

The FDA has approved BioMarin’s pegvaliase-pqpz (Palynziq), a drug for the treatment of phenylketonuria (PKU) in adults. PKU is a rare autosomal recessive disorder, affecting approximately 1 in every 10,000 to 15,000 people in the United States, that increases the levels of phenylalanine (an amino acid obtained through all dietary proteins and some artificial sweeteners) in the blood. If not treated, PKU may result in a buildup of phenylalanine, which is toxic to brain tissue and can lead to intellectual disability.

Pegvaliase-pqpz, which is approved to treat patients whose phenylalanine concentrations are above 600 micromol/L on their existing management, is a pegylated recombinant phenylalanine ammonia lyase enzyme that helps the body to break down phenylalanine.

"BioMarin is thrilled to be able to offer this important new therapy to adults with PKU who are unable to control their [phenylalanine] levels with existing options,” Jean-Jacques Bienaimé, chairman and CEO of BioMarin, said in a statement. “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."

Approval of the drug was based on results of the phase 3 PRISM-2 study. Part 2 of the 4-part study was an 8-week randomized discontinuation trial (RDT) that evaluated the change in blood phenylalanine concentrations, neuropsychiatric and neurocognitive measures, and safety outcomes in study participants who had already achieved at least a 20% reduction in blood phenylalanine from pretreatment baseline with pegvaliase. Patients were randomized 2:1 to either continue pegvaliase at doses of either 20 mg/day or 40 mg/day, or switch to a matching placebo.

The study met its primary endpoint—change in blood phenylalanine from RDT entry to week 8&mdash;with clinically meaningful, statistically significant differences between the treatment and placebo groups. At week 8, the least squares mean change (95% CI for all) in blood phenylalanine was 949.8&#8239;μM (range, 760.4-1139.1) for the 20&#8239;mg/day placebo group and 664.8&#8239;μM (range, 465.5-864.1) for the 40&#8239;mg/day placebo group versus 26.5&#8239;μM (−68.3-121.3) for the pooled pegvaliase group (P &#8239;<.0001).

The most common adverse events associated with pegvaliase treatment during the study were arthralgia, headache, anxiety, fatigue, and upper respiratory tract infection.

BioMarin reports that the drug is expected to become available at the end of June 2018 and will be available through a restricted program under a Risk Evaluation and Mitigation Strategy program.

Reference

Harding CO, Amato RS, Stuy M, et al. Pegvaliase for the treatment of phenylketonuria: a pivotal, double-blind randomizeddiscontinuation Phase 3 clinical trial. Mol Genet Metab. 2018;124(1):20-26. doi: 10.1016/j.ymgme.2018.03.003.