Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics

Abstract

Objective To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers. Methods Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings. Results Fifteen cases of adults with PKU (eight males, seven females), representing a spectrum of age (18 to 53 years), previous PKU care, comorbidities, and socioeconomic situations were reviewed and discussed. Full extended case reports are included in the Supplement. The cases showed that treating patients with a daily injectable can be challenging due to a patient's financial problems, treatment challenges, and neuropsychological and psychiatric comorbidities, which can be identified before starting pegvaliase, but do not prohibit successful treatment. The authors agreed that patient education on adverse events (AEs), time to efficacy, dietary changes, and food preparation is an ongoing process that should start prior to initiating pegvaliase treatment. Treatment goals and planned dietary changes once efficacy is reached should be defined prior to treatment initiation and re-evaluated throughout the course of therapy. Each patient's titration schedule and dietary adjustments are unique, depending on occurrence of AEs and individual goals of treatment. Despite the AE profile of pegvaliase, all but two patients remained motivated to continue treatment and achieved efficacy (except one patient in whom titration was still ongoing). AEs occurring early in the treatment pathway may require prolongation of the titration phase and/or concomitant medication use, but do not seem indicative of future tolerability or eventual efficacy. Close follow-up of patients during titration and maintenance to help with dietary changes is important. Conclusion This case series provides real-world experience on the use of pegvaliase. Until data from registries and independent research become available, the data presented herein can support appropriate management of patients receiving pegvaliase in clinical practice.

Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria

“…These benefits are related to the increase in Phe tolerance, reducing the practical impact of dietary treatment [ 66 , 82 , 107 , 108 ]. For pegvaliase, preliminary case reports and expert opinions similarly report improvements in the QoL of adults with PKU related to the ability of patients to consume a more normal diet [ 109 ].…”

Pre-analytic decrease of phenylalanine in plasma of patients with phenylketonuria treated with pegvaliase

“…Early identification and implementation of a Phe-restricted diet can avoid the most severe symptoms associated with untreated PKU [ 1 ]. While early treatment for PKU relied entirely on dietary restriction, over the last two decades improvements have been achieved, including medications to enhance residual PAH activity [ 2 , 3 ], and enzyme-based treatments that metabolize Phe via alternate pathways [ 4 , 5 ]. Pegvaliase, is a pegylated form of phenylalanine ammonia lyase (PAL), an enzyme which converts Phe to ammonia and trans-cinnamic acid.…”

Real-world treatment, dosing, and discontinuation patterns among patients treated with pegvaliase for phenylketonuria: Evidence from dispensing data

“…Several case series of pegvaliase use in the real world have documented use of alternative dosing regimens, and have noted that some patients appear to be able to require lower doses of pegvaliase than the dose at which they initially responded to maintain blood Phe levels in a desired treatment range [ [12] , [13] , [14] , [15] ]. These publications have also identified patients who have discontinued pegvaliase therapy at various points in the treatment journey, for reasons both related and unrelated to drug tolerability.…”