Palynziq ‘Challenging’ But ‘Powerful’ Treatment for PKU, Real-life Study Reports

Palynziq ‘Challenging’ But ‘Powerful’ Treatment for PKU, Real-life Study Reports
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The enzyme substitution therapy Palynziq (pegvaliase-pqpz) lowered blood phenylalanine levels in most adults with phenylketonuria (PKU) treated at the PAL Clinic of Boston Children’s Hospital, a study reported.

Side effects were common but adequately managed, allowing for treatment to continue in most patients.

The study, “First 1.5 years of pegvaliase clinic: Experiences and outcomes,” was published in the journal Molecular Genetics and Metabolism Reports.

People with PKU have a toxic buildup of the amino acid phenylalanine — one of the building blocks of proteins — and must rely on a diet low in phenylalanine to help prevent disease complications.

Palynziq, developed by BioMarin Pharmaceutical, is an alternative when standard treatments, including dietary phenylalanine restriction and medical foods, fail to achieve target blood phenylalanine concentrations — typically between 120 and 360 micromol (mcmol)/L.

The at-home therapy is given daily by subcutaneous (under-the-skin) injection, and approved for adults with PKU, potentially allowing less restricted diet plans. Palynziq is composed of a modified form of the enzyme phenylalanine ammonia lyase (PAL), which breaks down phenylalanine. 

The PAL Clinic is a PKU specialty center that provides care for patients receiving Palynziq. Clinicians give ongoing education and support regarding the administration, safety, and efficacy of Palynziq before and throughout treatment.

Researchers reported on the first 1.5 years of  their clinic’s use of this therapy in 46 patients. Twenty had transitioned from clinical trials, 25 were new patients, and one was transferred to the clinic. Their mean age was 35.9, ranging from 19 to 55 years old. 

Patients moving from clinical trials had already been treated for an average of about five years. At their first clinic visit, four had blood phenylalanine over 360 mcmol/L, two were within 30–360 mcmol/L, and 11 had blood phenylalanine levels of less than 30 mcmol/L. No data were available for the three other patients. 

Adherence to the therapy declined in six patients after the trials, and clinic staff increased contact to help with consistent dosing. 

For injection fatigue, the clinic offered higher doses in a single injection fewer times each week, in which phenylalanine levels remained consistent. Weekly doses were reduced in patients with lower than 30 mcmol/L of phenylalanine. No side effects were seen in those given lower doses.

“We advised dosing a minimum of twice weekly to avoid potential side effects from dose interruption,” the scientists wrote. 

Patients who started on Palynziq were treated for an average of 45 weeks (about 10 months). The mean blood phenylalanine level at baseline (study start) for these 26 people was 1,031 mcmol/L, which lowered in nine patients to 654 mcmol/L after one year of therapy. 

Results showed that nearly all (24) had a 30% or greater decrease in phenylalanine, with an overall average decline of 56%. In 18 patients (69%), a 50% or higher decrease was seen and corresponded to a blood phenylalanine concentration of less than 360 mcmol/L.

Some of these people reported improved quality of life, and better verbal communication and daily functioning. Objective data, however, were unavailable for most participants, the scientists said.

Sixteen people starting on Palynziq kept to a phenylalanine-restricted diet, eight had moderate protein restriction with inadequate medical food (not more of 50% of prescribed), and two stopped all dietary treatment. Among 18 patients with changed phenylalanine levels following treatment, nine tolerated a regular diet with no medical food.

Side effects were experienced by all, typically occurring one to two weeks after starting treatment, and included injection-site reactions, joint pain, rash, headache, fatigue, and dizziness. One person experienced a severe allergic reaction (anaphylaxis). 

Side effects lessened throughout treatment and were successfully managed, allowing treatment to continue in most patients. 

“While there are many challenges with [Palynziq] therapy, including a significant side-effect profile and delay of drug efficacy, it has proven to be a powerful new treatment for adults with PKU,” the investigators wrote. 

“As our clinic expands in the future with a broader PKU population base, we hope to continually improve clinic practices involving this new treatment modality,” they added. 

Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
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