Most patients with phenylketonuria were unwilling to start treatment with Palynziq (pegvaliase-pqpz) due to concerns about its safety and the need to self-inject the medication under the skin, according to a small study in Germany.
The findings also suggest that many patients can control their blood levels of phenylalanine solely through a restricted diet without any further interventions.
The study, titled “Case-control study about the acceptance of Pegvaliase in Phenylketonuria,” was published in the journal Molecular Genetics and Metabolism Reports.
Palynziq is the first enzyme substitution therapy, developed by Biomarin, that has been approved for phenylketonuria (PKU), a genetic brain-threatening condition marked by an inability to break down the amino acid phenylalanine, one of the build blocks of proteins, from dietary protein.
The medicine was approved in 2018 to treat adults with PKU in the U.S., and more recently in May 2019 to treat patients 16 years or older in the European Union.
Palynziq is used to reduce phenylalanine levels in patients whose blood levels of phenylalanine have not been adequately controlled with other treatments.
The therapy is made of a bacterial enzyme that can break down phenylalanine, thereby preventing it from building up to toxic levels in the body and helping to relieve PKU symptoms. The enzyme is “pegylated” (attached to a chemical called PEG), which enables it to remain active in the body for longer.
As this enzyme is isolated from bacteria, it can provoke adverse immune reactions in patients, who develop antibodies against PEG or the bacterial enzyme. For this reason, the treatment reportedly can lead to side effects in up to 90% of patients.
“A trained observer must be present for an hour after every injection,” the study noted. “Thus, the selection of the right patient for a potential harmful treatment is essential for patient’s contentedness and long-term therapy compliance.”
Moreover, the medicine is delivered via pre-filled syringes to be injected under the skin (subcutaneously), which may also be inconvenient.
Given these potential shortfalls, Johannes Krämer, a researcher at the Children’s Hospital, University of Ulm, in Germany, conducted a study to assess acceptance of Palynziq among patients.
He selected 45 PKU patients referred to the hospital, who were eligible to receive Palynziq, and invited each to undergo a routine examination and an informal conversation about new treatment options, including Palynziq.
Twenty-six of these patients agreed to receive this information, and their clinical data and plasma phenylalanine blood levels were measured.
Within this group, 12 patients (46%) were females, and 23 (89%) patients said they were sticking to a phenylalanine-restricted diet.
Patients had four weeks to decide if they were willing to start Palynziq.
Seven patients (27%) agreed to start the treatment while 19 (73%) declined. The main reasons cited for rejecting the therapy were fear of adverse effects (47%), no need for additional treatment (26%), and the requirement to inject the medication (21%). One patient refused for personal reasons.
Before treatment, phenylalanine levels in the group that agreed to start Palynziq were higher (about 1180 μmol/l) compared to the group who declined the treatment (about 930 μmol/l).
Of note, after four weeks, patients on Palynziq had stable levels of phenylalanine (1264 μmol/l compared with 1180 μmol/l at the beginning of the study), while patients who did not take the medicine experienced a significant reduction in those levels (930 μmol/l vs. 779 μmol/l at baseline) without any interventions besides a restricted diet.
“PKU patients have reservations against an invasive subcutaneous treatment for their disease. This is mainly caused by the form of application by syringe and the potential harmful side effects. Only less than one-third of the patients in our cohort are willing to start treatment,” Krämer stated.
Contrary to a recent study showing that patients with PKU are willing to accept the risks of hypersensitivity reactions to optimize their treatment, “we could clearly show the patients reservation against the invasive treatment of their disorder,” the researcher said.
One aspect is the different management of PKU in Europe for the last decade, which permitted looser thresholds for phenylalanine levels of about 1200 μmol/l, according to the study.
“Most PKU patients seem to have untapped potential for self-contained reduction of Phe [phenylalanine] levels only by being focused on their diet,” the study added. “Therefore, regular professional nutritional advice, even in adult patients with supposed high knowledge in Phe-restricted diet, is sufficient to significantly reduce Phe-levels within short periods of time.”