Rare Disease Report

Pivotal BioMarin PKU Study Meets Primary Endpoint While Patients NOT on a Phe-Restricted Diet

MARCH 21, 2016
James Radke, PhD

A treatment for phenylketonuria (PKU) patients that allows them to eat protein may soon be available. Today, BioMarin announced their pivotal Phase 3 studies testing their developmental drug pegvaliase met the primary endpoint of change in blood Phe in patients with PKU compared to those given a placebo.  And the group did this while not eating a Phe-restricted diet.

Patients in the trial were estimated to be eating 75% of the daily recommended allowance for protein intake for a healthy adult.

In the 86 patient trials, the pegvaliase treated group maintained mean blood Phe levels at 527.2 umol/L compared to their baseline of 503.9 umol/L, whereas the placebo treated group mean blood Phe levels increased to 1385.7 umol/L compared to their baseline of 536.0 umol/L .

In the secondary endpoints, no benefit in inattention or mood scores were observed between the 2 groups following 8 weeks of treatment however, the company noted that long term evaluations have shown some improvement with inattention while patients were taking pegvaliase.

It should be noted that practice guidelines issued by the American College of Medical Genetics and Genomics (ACMG) support the need for lifelong management of Phe levels in PKU patients.  The guidelines state that the treatment goal for PKU patients should be blood levels of phenylalanine (Phe) for all patients between 120-360 umol/L. The Long Term open label portion of the PRISM-2 study demonstrated sustained and substantial reductions in Phe levels.  Of the 90 patients who had been treated for at least 41 weeks in this portion of PRISM-2, 40% had achieved a Phe level of 120 umol/L or less (120 umol/L is considered the upper limit of normal), 60% had achieved a Phe level of 360 umol/L or lower (the target Phe level according to the ACMG guidelines) and 79% had achieved a Phe level reduction of 20% or greater.

BioMarin hopes to submit a marketing application by the end of the year. 

Quotes about the study

“We are pleased that the double-blind, randomized, placebo-controlled part of the PRISM-2 trial demonstrated strong blood Phe reduction in pegvaliase treated patients whose dietary protein intake was unrestricted at baseline and maintained throughout the study.  We are committed to the global PKU community and to bringing them a medicine that has the potential to treat PKU adult patients,” said Hank Fuchs, M.D., Chief Medical Officer at BioMarin.  “We look forward to sharing this data with the regulatory authorities in the US and Europe to continue the process of bringing an important therapy to patients.”
 
“Treatment with pegvaliase has resulted in dramatic Phe decreases down to within normal levels which have not been achievable in the past with other PKU treatment options.  We are grateful to the patients who participated in this important trial.  Blood Phe reductions at this level have the potential to have a meaningful impact on the lives of PKU patients,” said Cary Harding, M.D. Professor of Molecular and Medical Genetics and Pediatrics at Oregon Health & Science University and investigator for the pegvaliase Phase 3 program.
 
“A therapy in development that shows such a substantial reduction in Phe levels could mean that for the first time, PKU patients who cannot comply with dietary protein restriction, can achieve targeted blood Phe levels,” said Barbara Burton, M.D., Professor of Pediatrics-Genetics, Birth Defects and Metabolism at Northwestern School of Medicine and investigator for the pegvaliase Phase 3 program.  “This pegvaliase study represents an important advance for PKU adult patients and a potentially meaningful treatment.”

Conference Call

BioMarin will host a conference call/webcasat today at 5:30am PDT/8:30am EDT today to discuss the results. Click here for more details.


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