Two years of pegvaliase in Germany: Experiences and best practice recommendations.

Background: In 2019, pegvaliase was approved in Europe for the treatment of phenylketonuria (PKU) in patients aged 16 years and older with blood phenylalanine (Phe) concentrations above 600 μmol/L despite prior management with available treatment options. Since its European approval, German metabolic centres have gained valuable experience, which may be of benefit to other treatment centres managing patients on pegvaliase.
Methods: After a virtual meeting that was attended by nine German physicians, three German dietitians and one American physician, a follow-up discussion was held via an online platform to develop a set of recommendations on the use of pegvaliase in Germany. Eight German physicians contributed to the follow-up discussion and subsequent consensus voting, using a modified Delphi technique. The recommendations were supported by literature and retrospectively collected patient data.
Results: Consensus (≥75% agreement) was achieved on 25 recommendations, covering seven topics deemed relevant by the expert panel when considering pegvaliase an option for the treatment of patients with PKU. In addition to the recommendations, a retrospective chart review was conducted in seven of the centres and included 71 patients who initiated treatment with pegvaliase. Twenty-seven patients had been treated for at least 24 months and 23 (85.2%) had achieved blood Phe ≤600 μmol/L with some degree of diet normalisation. Of these patients, 14 had physiological blood Phe on a normalised diet.
Conclusion: The practical consensus recommendations provide guidance on the different steps along the pegvaliase journey from clinical site requirements to treatment goals and outcomes. The recommendations are intended to support less experienced European metabolic centres with the implementation of pegvaliase, emphasising that a core treatment team consisting of at least a dietitian and metabolic physician is sufficient to initiate pegvaliase and support patients during their treatment journey.
Competing Interests: Declaration of Competing Interest JK received consulting payments and speaker fees from Amicus, BioMarin and Sanofi, as well as speakers fees from Shire and research grants from Danone. CB received consulting payments from BioMarin, participated as a clinical trial investigator for BioMarin and received speaker fees from Sanofi-Genzyme, Sobi and Vitaflo. CH and AR are employees of BioMarin Deutschland GmbH. CK received consulting payments from BioMarin. KGP received consulting payments from BioMarin and research fees as well as speaker fees from Vitaflo. FR received consulting payments from BioMarin, Elastrin Therapeutics and Inozyme Pharma, research grants and patents from Inozyme Pharma, speaker fees from BioMarin, Inozyme Pharma and Recordati Rare Diseases and participated as a clinical trial investigator for Aeglea BioTherapeutics, BioMarin, Inozyme Pharma and PTC Therapeutics. SS received consulting payments from BioMarin, Leadiant GmbH and Vertex, speaker fees and travel support from Sobi, and participated as clinical trial investigator for BioMarin. NW received consulting payments from BioMarin, Sanofi and Takeda, speaker fees from Sanofi and Takeda, travel support from Nutricia and Takeda and participated as a clinical trial investigator for BioMarin. ACM received consulting payment from Atheneum, Nestlé and PTC Therapeutics, speaker fees from AIM-PHAMRA Ltd., APR and Nutricia, travel support from Nutricia and participated as a clinical trial investigator for BioMarin and PTC Therapeutics.
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