PMID- 34430209 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220426 IS - 2214-4269 (Print) IS - 2214-4269 (Electronic) IS - 2214-4269 (Linking) VI - 28 DP - 2021 Sep TI - Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics. PG - 100790 LID - 10.1016/j.ymgmr.2021.100790 [doi] LID - 100790 AB - 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. CI - (c) 2021 The Authors. FAU - Adams, Darius AU - Adams D AD - Atlantic Health Morristown Medical Center, Morristown, NJ, USA. FAU - Andersson, Hans C AU - Andersson HC AD - Hayward Genetics Center, Tulane University Medical School, New Orleans, LA, USA. FAU - Bausell, Heather AU - Bausell H AD - Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. FAU - Crivelly, Kea AU - Crivelly K AD - Hayward Genetics Center, Tulane University Medical School, New Orleans, LA, USA. FAU - Eggerding, Caroline AU - Eggerding C AD - Cooper University Health Care, Camden, NJ, USA. FAU - Lah, Melissa AU - Lah M AD - Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Lilienstein, Joshua AU - Lilienstein J AD - BioMarin Pharmaceutical Inc., Novato, CA, USA. FAU - Lindstrom, Kristin AU - Lindstrom K AD - Phoenix Children's Hospital, Phoenix, AZ, USA. FAU - McNutt, Markey AU - McNutt M AD - University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Ray, Joseph W AU - Ray JW AD - University of Texas Medical Branch, Galveston, TX, USA. FAU - Saavedra, Heather AU - Saavedra H AD - The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA. FAU - Sacharow, Stephanie AU - Sacharow S AD - Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Starin, Danielle AU - Starin D AD - Rare Disease Institute, Children's National, Washington, DC, USA. FAU - Tiffany-Amaro, Jennifer AU - Tiffany-Amaro J AD - St. Christopher's Hospital for Children, Philadelphia, PA, USA. FAU - Thomas, Janet AU - Thomas J AD - University of Colorado School of Medicine, Aurora, CO, USA. FAU - Vucko, Erika AU - Vucko E AD - Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. FAU - Wessenberg, Leah B AU - Wessenberg LB AD - OHSU Doernbecher Children's Hospital, Portland, OR, USA. FAU - Whitehall, Kaleigh AU - Whitehall K AD - BioMarin Pharmaceutical Inc., Novato, CA, USA. LA - eng PT - Journal Article DEP - 20210814 PL - United States TA - Mol Genet Metab Rep JT - Molecular genetics and metabolism reports JID - 101624422 PMC - PMC8369061 OTO - NOTNLM OT - ACMG, American College of Medical Genetics and Genomics OT - AEs, adverse events OT - Adverse events OT - BH4, tetrahydrobiopterin OT - Case series OT - HCP, healthcare provider OT - I/T/M, induction, titration, and maintenance OT - PAH, phenylalanine hydroxylase OT - PEGylated phenylalanine ammonia lyase OT - PKU diet OT - PKU, phenylketonuria OT - Pegvaliase OT - Phe, phenylalanine OT - Phenylketonuria COIS- DA reports grants from BioMarin outside the submitted work. HCA and KC received payments from BioMarin to participate in the advisory board meeting related to the submitted work. HB reports personal fees from BioMarin related to the submitted work and personal fees from BioMarin, Cambrooke, Horizon, Nutricia, Ultragenyx, and Vitaflo outside the submitted work. CE received payments from BioMarin to participate in the advisory board meeting related to the submitted work, and payments from BioMarin outside the submitted work. ML received personal fees to participate in the advisory board meeting related to the submitted work; payments from BioMarin outside the submitted work; and is an investigator in clinical trials sponsored by BioMarin. JL and KW are employees of BioMarin. KL received payments from BioMarin for participating in the advisory board meeting related to the submitted work; she is currently an employee of BioMarin. MM reports personal fees and non-financial support from BioMarin related to the submitted work and personal fees from Applied Therapeutics, Cycle Pharmaceuticals and Rhythm Pharmaceuticals, personal fees and non-financial support from Aeglea Biotherapeutics and Horizon Therapeutics, and grants from Censa Pharmaceuticals outside the submitted work. JWR received payments and travel support from BioMarin for participating in the advisory board meeting related to the submitted work. HS received payments and travel support from BioMarin related to the submitted work, was involved as an investigator in clinical trials for BioMarin, and received payments from BioMarin, Vitaflo, MetEd and Symbiotics outside the submitted work. SS received consulting fees, speaker fees, and travel support from BioMarin and was involved as an investigator in clinical trials for BioMarin. DS received personal fees from BioMarin related to the submitted work and personal fees from BioMarin, Cambrooke, Horizon, Nutricia, Ultragenyx, Cycle Pharmaceuticals and Vitaflo outside the submitted work. JT-A received personal fees for participating in the advisory board related to the submitted work and personal fees from BioMarin outside the submitted work. JT was involved as an investigator in clinical trials for BioMarin and was a member of the Phase III advisory board. EV received personal fees for participating in the advisory board related to the submitted work and personal fees from BioMarin outside the submitted work. LBW received personal fees from BioMarin for participating in the advisory board and virtual platform meeting related to the submitted work, and personal fees from BioMarin and Nutricia outside the submitted work. EDAT- 2021/08/26 06:00 MHDA- 2021/08/26 06:01 PMCR- 2021/08/14 CRDT- 2021/08/25 06:25 PHST- 2021/07/01 00:00 [received] PHST- 2021/08/03 00:00 [accepted] PHST- 2021/08/25 06:25 [entrez] PHST- 2021/08/26 06:00 [pubmed] PHST- 2021/08/26 06:01 [medline] PHST- 2021/08/14 00:00 [pmc-release] AID - S2214-4269(21)00084-7 [pii] AID - 100790 [pii] AID - 10.1016/j.ymgmr.2021.100790 [doi] PST - epublish SO - Mol Genet Metab Rep. 2021 Aug 14;28:100790. doi: 10.1016/j.ymgmr.2021.100790. eCollection 2021 Sep.