Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM).

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Thomas J, Levy H, Amato S, Vockley J, Zori R, Dimmock D, Harding CO, Bilder DA, Weng HH, Olbertz J, Merilainen M, Jiang J, Larimore K, Gupta S, Gu Z, Northrup H

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. doi: 10.1016/j.ymgme.2018.03.006. Epub 2018 Mar 31.

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29653686 [ View in PubMed
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Abstract

BACKGROUND: Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) deficiency that results in phenylalanine (Phe) accumulation. Pegvaliase, PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL), converts Phe to trans-cinnamic acid and ammonia, and is a potential enzyme substitution therapy to lower blood Phe in adults with PKU. METHODS: Two Phase 3 studies, PRISM-1 and PRISM-2, evaluated the efficacy and safety of pegvaliase treatment using an induction, titration, and maintenance dosing regimen in adults with PKU. In PRISM-1, pegvaliase-naive participants with blood Phe >600mumol/L were randomized 1:1 to a maintenance dose of 20mg/day or 40mg/day of pegvaliase. Participants in PRISM-1 continued pegvaliase treatment in PRISM-2, a 4-part clinical trial that includes an ongoing, open-label, long-term extension study of pegvaliase doses of 5mg/day to 60mg/day. RESULTS: Of 261 participants who received pegvaliase treatment, 72.0% and 32.6% reached >/=12months and>/=24months of study treatment, respectively, and 65% are still actively receiving treatment. Mean (SD) blood Phe was 1232.7 (386.4) mumol/L at baseline, 564.5 (531.2) mumol/L at 12months, and 311.4 (427) mumol/L at 24months, a decrease from baseline of 51.1% and 68.7%, respectively. Within 24months, 68.4% of participants achieved blood Phe

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