Phenylketonuria: Palynziq (pegvaliase)
Indication: Indicated to reduce blood phenylalanine concentrations in adults with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations >600 μmol/L on existing management.
Mechanism: Pegvaliase is a PEGylated phenylalanine ammonia lyase (PAL) that substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme activity in patients with PKU, thereby reducing blood phenylalanine concentrations.
Induction: 2.5 mg SC once weekly for 4 weeks
Titration: Based on tolerability, titrate dose in a stepwise manner over at least 5 weeks, to achieve a dosage of 20 mg SC once daily; additional time may be needed for dose escalation depending on tolerability.
Maintenance: Maintain at 20 mg SC once daily for at least 24 weeks; may increase, but should not exceed 40 mg/day in patients who have been maintained continuously on 20 mg/day for at least 24 weeks and who have not achieved a 20% reduction in blood phenylalanine concentration from pretreatment baseline.
Approval was based on two phase 3 studies, PRISM-1 and PRISM-2, which evaluated the efficacy and safety of pegvaliase treatment using an induction, titration, and maintenance dosing regimen in adults with PKU. Of 261 participants who received pegvaliase, 72% and 32.6% reached ≥12 months and ≥ 24 months of study treatment, respectively, and 65% are still actively receiving treatment. Mean (SD) blood Phe was 1232.7 (386.4) μmol/L at baseline, 564.5 (531.2) μmol/L at 12 months, and 311.4 (427) μmol/L at 24 months, a decrease from baseline of 51.1% and 68.7%, respectively.
Thomas J, Levy H, Amato S, et al. Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM). Mol Genet Metab. 2018 May;124(1):27-38. https://www.ncbi.nlm.nih.gov/pubmed/29653686
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Cite this: Mary L Windle. FDA New Drug and Biologic Approvals, 2018 Midyear Review - Medscape - Aug 01, 2018.