First Enzyme Substitution Therapy Approved for Phenylketonuria in Adults

Palynziq is a PEGylated phenylalanine ammonia lyase enzyme
Palynziq is a PEGylated phenylalanine ammonia lyase enzyme

BioMarin announced that the Food and Drug Administration (FDA) has approved Palynziq (pegvaliase-pqpz) Injection to reduce blood phenylalalnine (Phe) levels in adults with phenylketonuria (PKU), who have uncontrolled Phe levels >600 µmol/L on existing management. This marks the first approved enzyme substitution therapy for PKU that works by helping the body break down Phe. 

Palynziq is a PEGylated phenylalanine ammonia lyase enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. It substitutes for the deficient phenylalanine hydroxylase enzyme activity in patients with PKU and reduces blood phenylalanine concentrations. Treatment with Palynziq consists of induction, titration, and maintenance phases; periodic blood Phe monitoring is recommended.

Palynziq was evaluated in 2 trials of adults with PKU who had blood Phe >600 µmol/L on current therapy; most patients were on an unrestricted diet before and during the trials. One study, an open-label, randomized, multicenter trial, evaluated increasing does of subcutaneous Palynziq up to a target dose of either 20mg or 40mg once daily. 

The second trial was a Phase 3, 8-week, placebo-controlled, randomized withdrawal trial (PRISM-2) in patients who were previously treated with Palynziq. Study patients were randomized (2:1) to either continue maintenance Palynziq 20mg or 40mg once daily or to receive matching placebo for a total of 8 weeks. The data showed patients who received Palynziq achieved statistically significant reductions in blood phenylalanine concentrations from their pre-treatment baseline blood Phe concentrations. 

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The most common adverse events reported in clinical trials included injection site reactions, joint pain, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus, nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough and diarrhea.The labeling for Palynziq carries a Boxed Warning regarding the risk of anaphylaxis; in clinical trials, anaphylaxis occurred most frequently during upward dose titration within the first year of treatment. Patients are required to have auto-injectable epinephrine available at all times during treatment.

Palynziq is anticipated to launch by the end of June 2018 as 2.5mg/0.5 mL, 10mg/0.5 mL, and 20mg/mL strength single-dose prefilled syringes. It will be available only through a Risk Evaluation and Mitigation Strategy (REMS) program. 

For more information call (866) 906-6100 or visit Palynziq.com.