A benefit-risk analysis of pegvaliase for the treatment of phenylketonuria: A study of patients' preferences

Sumitra SriBhashyam; Kevin Marsh; Adrian Quartel; Haoling H Weng; Ari Gershman; Nicola Longo; Janet Thomas; Roberto Zori

doi:10.1016/j.ymgmr.2019.100507

A benefit-risk analysis of pegvaliase for the treatment of phenylketonuria: A study of patients' preferences

Mol Genet Metab Rep. 2019 Aug 30:21:100507. doi: 10.1016/j.ymgmr.2019.100507. eCollection 2019 Dec.

Authors

Sumitra SriBhashyam¹, Kevin Marsh¹, Adrian Quartel², Haoling H Weng², Ari Gershman², Nicola Longo³, Janet Thomas⁴, Roberto Zori⁵

Affiliations

¹ Patient Centered Research, Evidera, The Ark, 201 Talgarth Road, Hammersmith, London W6 8BJ, UK.
² BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA.
³ Department of Pediatrics, Division of Medical Genetics, University of Utah, 295 Chipeta Way, Salt Lake City, UT 84108, USA.
⁴ Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado School of Medicine, 13123 East 16th Avenue, Aurora, CO 80045, USA.
⁵ Department of Pediatrics, Division of Genetics and Metabolism, University of Florida, Gainesville, FL 32610, USA.

Abstract

Background: Phenylketonuria (PKU) leads to an accumulation of phenylalanine (Phe) in the blood and subsequent neurologic, cognitive, psychiatric, and behavioral dysfunction. Many patients report social isolation and decreased quality of life. Pegvaliase is an enzyme substitution therapy that reduces blood Phe levels in patients with PKU and is associated with a risk of hypersensitivity reactions.

Objective: To define the minimum acceptable benefit (MAB) of pegvaliase, i.e., the minimum probability of achieving a blood Phe level <360 μmol/L, which patients require to tolerate the risks of hypersensitivity associated with pegvaliase.

Methods: Adult, pegvaliase-naïve patients with blood Phe levels >600 μmol/L participated in a patient-preference web survey using two surveys: adapted swing-weighting and thresholding. Participants were asked to make ordinal choices between varying clinical benefit and severity levels for hypersensitivity. Disease effects and treatment satisfaction were also assessed.

Results: Among 45 participants, the mean (standard deviation) self-reported blood Phe level was 976.9 (429.9) μmol/L; only 28.8% reported satisfaction with their current treatment. Most (84.4%) indicated difficulty in following a PKU diet; 60% reported that the PKU diet was burdensome, and 58% reported feeling socially isolated. Most (≥69%) reported their MAB to be less than the expected clinical benefit provided by pegvaliase; the mean MAB was 22.7% and 34.4% in the swing-weighting and thresholding surveys, respectively.

Conclusion: Most participants felt the burden of PKU on their daily lives, were dissatisfied with current treatments, and were willing to accept the risks of hypersensitivity reactions to achieve recommended blood Phe levels with pegvaliase treatment.

Keywords: ANOVA, analysis of variance; Benefit-risk analysis; FDA, Food and Drug Administration; IgE, immunoglobin E; MAB, minimum acceptable benefit; Minimum acceptable benefit; PKU; PKU, phenylketonuria; Patient preference; Pegvaliase; Phe, phenylalanine; Phenylketonuria; SD, standard deviation; SE, standard error.