BioMarin announced positive preliminary results from the pivotal Phase 3 PRISM-2 study of pegvaliase for the reduction of blood phenylalanine (Phe) in patients with phenylketonuria (PKU).

PRISM-2 is a double-blind, placebo-controlled, randomized drug discontinuation trial (RDT) to evaluate the efficacy and safety of self-administered SC injections of pegvaliase 20mg/day or 40mg/day vs. placebo in patients with PKU, followed by an open-label extension. This is the first placebo-controlled study demonstrating the ability to improve Phe levels in PKU patients who do not have to follow a Phe-restricted diet at baseline. Patients who entered PRISM-2 met a pre-specified reduction in blood Phe of ≥20% (based on two consecutive assessments) from their pre-treatment baseline in the PRISM-1 feeder study. The primary endpoint is change from the RDT baseline in blood Phe at 8 weeks.

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Preliminary findings demonstrated that patients treated with pegvaliase achieved an approximately 62% improvement in blood Phe compared to placebo, meeting the study’s primary endpoint. The pegvaliase-treated group maintained mean blood Phe levels at 527.2umol/L compared to their RDT baseline of 503.9umol/L, while the placebo-treated group increased from their RDT baseline of 536umol/L to 1385.7umol/L (P<0.0001).

The long-term open label extension study of PRISM-2 demonstrated sustained and significant reductions in Phe levels. Of the 90 patients who were treated with pegvaliase for ≥41 weeks, 40% achieved a Phe level of ≤120umol/L, 60% achieved ≤360umol/L (the target Phe level according to the ACMG guidelines) and 79% achieved a Phe level reduction of ≥20%.

In the secondary endpoints of the 8 week RDT, no benefit in inattention or mood scores were observed in patients treated with pegvaliase compared to placebo.

Results from these studies will be presented at the Society of Inherited Metabolic Disorders in April 2016. BioMarin plans to submit a marketing application for pegvaliase by the end of this year.

Pegvaliase is an investigational drug that substitutes the phenylalanine hydroxylase (PAH) enzyme in PKU by breaking down Phe.

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