Derived from evidence and consensus based clinical practice

Initiating a pegvaliase response trial

Pegvaliase is an enzyme (phenylalanine ammonia lyase - PAL) substitution therapy that reduces blood phenylalanine (PHE) and is approved in the U.S. for use in adults >18 years with PKU whose blood PHE >600 µmol/L on current therapy, and in Europe for adults >16 years. Pegvaliase has been used in adolescents, individuals with neurocognitive deficits (including late-treated adults), and individuals with blood PHE <600 µmol/L. Clinic protocols for initiating therapy generally follow published guidelines and/or the drug prescribing information. Setting clear expectations and understanding the individual's goals are critical to success. Initiating therapy, including dose titration and adverse event management, emphasizes individualizing treatment based on tolerance to the drug. Best practices for guiding individuals with PKU on pegvaliase therapy, including medical and nutrition management, as well as education and support strategies, continue to emerge.

Monitoring

Monitoring the clinical and nutritional status of an individual with PKU on pegvaliase therapy is necessary considering the inherent limitations of the PKU diet that can result in increased risk for nutritional deficiencies. Assessment of dietary intake (specifically protein), nutrient analysis, and evaluation of clinical signs and symptoms of nutritional insufficiencies in addition to biochemical monitoring of PHE, tyrosine (TYR) and markers of at-risk nutrients are critical to the successful unrestriction or normalization of the diet of an individual on pegvaliase therapy.

Managing pegvaliase treatment after response to therapy

After an individual's response to pegvaliase therapy the treatment goal is to establish life-long control of blood PHE concentrations (<360 µmol/L and >30 µmol/L) that lead to cognitive, psychosocial, and nutritional benefit. Contributing to these improvements is the ability to unrestrict or normalize diet while maintaining blood PHE control. Intact protein is added incrementally (10-20g), while medical food protein is decreased by similar amounts, until the DRI for dietary protein is met or exceeded. Hypophenylalaninemia (hypoPHE) and deficiency of blood TYR must be prevented. A positive outcome takes into account an individual's preferences and goals. It may include any beneficial reduction in blood PHE (as determined by the clinic), and any degree of diet liberalization and/or continuation of medical food that balances toleration of pegvaliase dosage (number of injections) required to control blood PHE.

Education and counseling to support normal nutrition with pegvaliase therapy

Education and counseling for individuals maintained on pegvaliase therapy is needed to optimize nutritional status. Because PKU dietary therapy is very restrictive, individuals (those who have accomplished adherence, as well as those who have not) must be educated in how to eat a nutritionally optimal diet (including protein quantity and quality, healthy energy intake, and micronutrient sufficiency). Individuals may have difficulty accepting high protein foods that were previously not allowed. Counseling and education should address appropriate food choices as well as food purchasing and preparation, and weight management.

Pegvaliase in special populations:

There is limited evidence on pegvaliase use in pregnant and lactating women as they were excluded from the drug clinical trials. However, subsequent case studies indicate that pegvaliase has been used successfully in pregnancy and is likely to be safe during lactation. Pegvaliase was studied in a small number of children aged 16 years and older in the early phases of the clinical trials, and it is approved in this age group in Europe. No experience of pegvaliase therapy in children under 16 has yet been published.