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. 2024 Dec 26:42:101181.
doi: 10.1016/j.ymgmr.2024.101181. eCollection 2025 Mar.

Lessons learned from 5 years of pegvaliase in US clinics: A case series

Erin Cooney  1 , Zineb Ammous  2 , Tricia Bender  3 , Gillian E Clague  3 , Marilyn Clifford  4 , Angela Crutcher  5 , Laura Davis-Keppen  6 , Kirsten Havens  7 , Melissa Lah  8 , Stephanie Sacharow  9 , Amarilis Sanchez-Valle  10 , Erika Vucko  7 , Bridget Wardley  3 , Leah Wessenberg  11 , Hans C Andersson  12
Affiliations

Lessons learned from 5 years of pegvaliase in US clinics: A case series

Erin Cooney et al. Mol Genet Metab Rep. .

Abstract

Objective: To provide insights and strategies for pegvaliase management in challenging cases with phenylketonuria (PKU) based on the first 5 years of experience with pegvaliase in real-world clinical practice.

Methods: Twelve PKU experts gathered during a one-day, in-person meeting to discuss clinical cases illustrating important lessons from their experiences treating patients with pegvaliase in real-world clinical practice. Challenges with pegvaliase experienced prior to and during treatment and corresponding strategies to overcome them were discussed.

Results: Twelve cases of adults with PKU (eight females and four males, aged 18 to 68 years) receiving pegvaliase were reviewed and discussed. Challenges of the cases included medical or mental health comorbidities, executive function deficits, challenging social or socioeconomic situations, logistical or geographic barriers, or a combination of these; one was considering pregnancy. Despite challenges, pegvaliase was initiated successfully in most cases. Strategies to overcome barriers included individualized education, including side effect action plans, help from support organizations, collaboration with local providers, and use of telemedicine. Recommendations from the clinicians included that comorbid conditions should be monitored closely after treatment initiation and may require collaboration with other healthcare providers. A collaborative relationship with the clinic, ongoing education, and supportive relatives or friends can help individuals to remain adherent to pegvaliase. Suboptimal adherence may be addressed by a daily reminder system, telemedicine, in-home support, or a modified titration plan. Treated individuals with eating disorders require additional follow-up and support to achieve a healthy relationship with food. In most cases, including late-diagnosed individuals, reduced blood Phe levels resulted in improved PKU-related symptoms, including neurological issues.

Conclusion: Experience from the presented cases and 5 years of expert experience with pegvaliase in the real-world setting provide insight and guidance for healthcare professionals initiating and managing pegvaliase treatment in complex PKU cases. These cases demonstrate that, through comprehensive assessment and addressing barriers, pegvaliase treatment can be successful in adults with PKU, regardless of prior treatment success, age, socioeconomic, cognitive, or executive function challenges, as well as in those with comorbidities or considering pregnancy. Ongoing documentation of clinical experience is crucial for advancing the management of individuals receiving this treatment.

Keywords: Case series; Expert opinion; PKU; Pegvaliase; Phenylketonuria; Treatment.

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Conflict of interest statement

The expert panel was compensated for their participation in the in-person advisory board. Erin Cooney received compensation from BioMarin for attending an advisory board related to this manuscript. Zineb Ammous is a consultant for Mirum pharmaceuticals and had attended advisory board meetings for Moderna. Marilyn Clifford received compensation from BioMarin for attending an advisory board related to this manuscript. Angela Crutcher received compensation for attending advisory boards, institutional payments, and travel support from BioMarin. Laura Davis-Keppen received compensation from BioMarin for attending meetings from BioMarin. Kirsten Havens received support for attending meetings from BioMarin, consulting fees from Zevra Therapeutics, and participated in advisory boards of BioMarin and Zevra Therapeutics. Melissa Lah received payments for attending advisory boards from BioMarin, PTC Therapeutics and Travere Therapeutics and is a Principal Investigator on clinical trials for BioMarin and PTC Therapeutics. Stephanie Sacharow has been an investigator and/or advisor for BioMarin, PTC Therapeutics, Jnana Therapeutics, and Synlogic. She has not personally accepted payment from BioMarin advisory activities since 2018. Amarilis Sanchez-Valle is Principal Investigator for clinical trials of Alexion, BioMarin, Jnana, Homology, Recordati, and Ultragenyx and received payments for lectures and advisory boards from Amgen, Acer, Applied Therapeutics, BioMarin, Jnana, Sanofi and Ultragenyx. Erika Vucko received consulting fees and payments for lectures, attending meetings and/or advisory boards from BioMarin, PTC Therapeutics, and Horizon. Leah Wessenberg received payments for participating in advisory boards from BioMarin and Javygtor. Hans C. Andersson is Co-Principal Investigator in ongoing BioMarin clinical studies. Tricia Bender, Gillian E. Clague, and Bridget Wardley are employees and stockholders of BioMarin.

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