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Phenylketonuria (PKU) results from a lower amount of an enzyme activity called phenylalanine hydroxylase (PAH) than usual. Because of this, people with PKU cannot process one of the amino acids found in many foods. The amino acid, called phenylalanine or "Phe" for short, builds up in the body and blood. Too much Phe is toxic to the brain and can cause many problems. In infants and children, if PKU is not treated, the resulting high Phe can cause severe mental retardation. Even if PKU is treated with dietary changes, problems like lower intelligence (IQ), poor focus, mood swings, being irritable, depressed, slow reaction time and other problems may still occur. Worldwide, PKU occurs in about 1:10,000 live births. It is inherited in an autosomal recessive manner, affects males and females equally, and in most cases, both parents of an affected child are asymptomatic carriers of the disease.

Program Overview

There are two different study drugs being studied for PKU—Kuvan® and PEG-PAL.

Kuvan® at a Glance

Kuvan® (sapropterin hydrochloride) Tablets are the first and only FDA-approved medication for PKU to reduce blood Phe levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin (BH4-) responsive PKU. Kuvan® is a form of BH4, the natural cofactor for the PAH enzyme, which stimulates activity of the residual PAH enzyme to metabolize Phe into tyrosine. Kuvan® is to be used in conjunction with a Phe-restricted diet.

  • Manufactured and commercialized by BioMarin in the United States and Canada
  • Approved in the United States, Canada, and other markets. Indications vary by country of approval.
  • Designated an orphan drug in the United States and European Union
  • Additional clinical studies using Kuvan® are ongoing

PEG-PAL at a Glance

PEG-PAL(PEGylated recombinant phenylalanine ammonia lyase or ‘PAL’) is a study drug that substitutes for the PAH enzyme in phenylketonuria (PKU). PEG-PAL is being developed as a potential treatment for patients whose blood Phe levels are not adequately controlled by Kuvan® or who have trouble controlling and maintaining their Phe levels.

  • BioMarin started clinical studies in humans in 2007 to evaluate safety and efficacy
  • PEG-PAL has been assigned the Orphan Drug designation in the United States and European Union

Patient Educational Information

Understanding Clinical Studies: Are They Right for You? (video):

You’ll hear from two leading PKU health care providers about the key elements of participating in a clinical study and answers to important questions that you may have about this. The experts are Laurie Bernstein, MS, RD and FADA, Assistant Professor in the Department of Pediatrics, Director of Inherited Metabolic Disease Nutrition, The Children’s Hospital Colorado and Jerry Vockley, MD, PhD, Chief of the Division of Medical Genetics at Children’s Hospital at Pittsburgh and professor of pediatrics at the University of Pittsburgh School of Medicine. They will be joined by Karlye and Ryan, an adult and adolescent with PKU who share their stories about participating in a clinical study.

Webcast “Understanding Clinical Studies” Please click here

This is the first webcast in the “Shared Experiences” Special Edition series focusing on clinical studies and Phenylketonuria (PKU). The program is 30-mintues and features two leading PKU health care providers and a person with PKU.

Webcast “An Update on BioMarin PKU Clinical Studies” Please click here

This webcast features a leading PKU health care provider and discusses a number of the current BioMarin PKU clinical studies

Current Clinical Trials

To learn more about current PKU Research Opportunities and the ability to take a screening questionnaire to see if you may qualify to join one of the studies, please click here

Kuvan®

1. Phase 3b Open-Label Study to Evaluate the Effect of Kuvan® on Neurocognitive Function, Maintenance of Blood Phenylalanine Concentrations, Safety, and Population Pharmacokinetics in Young Children With Phenylketonuria (PKU-015):

This study is evaluating the effect of Kuvan® on long-term neurocognitive function, safety, growth and maintenance of Phe levels in young children with PKU.

Key Study Facts:

  • The participants’ neurocognitive function and growth will be assessed
  • Enrolling PKU patients ages: 0-6 years; currently enrolling 2-4 year olds only
  • The study will last up to 7 years
  • The study will include 24 scheduled doctor visits

For additional information about the study, including details about participating centers, please click here

2. A Double-blind, Placebo-controlled, Randomized Study to Evaluate the Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Subjects With Phenylketonuria (PKU-016):

This study is evaluating an investigational drug, sapropterin dihydrochloride, for people with PKU who also experience other symptoms such as anxiety, depression, difficulty concentrating, or lack of focus to determine whether it will help these symptoms.

Key Study Facts

  • Enrolling PKU patients ages: greater than or equal to 8 years
  • The study will last up to 32 weeks
  • The study will include 8 doctor visits
  • During 13 weeks of the study, patients will have a 50% chance of receiving placebo instead of the study drug
  • Participants will need to maintain the same diet they have been on for the past 3 months

For additional information about the study, including details about participating centers, please click here

3. PKUDOS – Phenylketonuria (PKU) Demographic, Outcomes and Safety Registry

This study is looking at safety and long term outcome over time when exposed to Kuvan®.

Key Study Facts

  • Enrolling PKU patients of all ages
  • Observational program for patients with PKU who have either received Kuvan® therapy, or currently receive Kuvan®, or intend to begin receiving Kuvan® therapy within 90 days of entering the registry
  • Includes a subregistry for pregnant mothers

For additional information about the study, including details about participating centers, please click here

PEG-PAL

1. Phase 2, Open-Label Dose-Finding Study to Evaluate the Safety, Efficacy, and Tolerability of Multiple Subcutaneous (SC) Doses of rAvPAL-PEG in Subjects With PKU (PAL-002):

This study is evaluating the safety, tolerability, and effectiveness of weekly injections of an investigational drug for people with PKU who have trouble controlling and maintaining their Phe levels.

Key Study Facts:

  • Enrolling PKU patients between the ages of 16 and 55 years, inclusive
  • Participants will receive weekly dosing of study drug
  • The initial study will last up to 22 weeks, and the participants will have the option to take part in an extension study up to 2 additional years
  • The study will include people with PKU who have tried Kuvan® for at least 4 weeks, but are not currently taking it because their response was insufficient as determined by their physician
  • The study will also include people with PKU who have tried Kuvan® but abandoned it for reasons of non-compliance and have been off Kuvan® for at least 6 months
  • Participants must be willing to maintain their current diet throughout the study

For additional information about the study, including details about participating centers, please click here

2. A Phase 2, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Subcutaneous Dose Levels of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria (PAL-004):

This study is evaluating the safety, tolerability, and effectiveness of daily injections of an investigational drug for people with PKU who have trouble controlling and maintaining their Phe levels.

Key Study Facts:

  • Enrolling PKU patients between the ages of 16 and 70 years, inclusive
  • Participants will receive daily dosing of study drug
  • The study will last up to 16 weeks, and the participant will have the option to take part in an extension study up to 2 additional years
  • The study will include people with PKU who have tried Kuvan® for at least 4 weeks, but are not currently taking it because their response was insufficient as determined by their physician
  • The study will also include people with PKU who have tried Kuvan® but abandoned it for reasons of non-compliance and have been off Kuvan® for at least 4 months
  • Participants must be willing to maintain their current diet throughout the study

For additional information about the study, including details about participating centers, please click here

3. Long-term Extension of a Phase 2, Open-Label Dose-Finding Study to Evaluate the Safety, Efficacy, and Tolerability of Multiple Subcutaneous Doses of rAvPAL-PEG in Subjects With PKU

This study is evaluating the long term safety, tolerability and effectiveness of injections of an investigational drug for people with PKU who have trouble controlling and maintaining their Phe levels.

Key Study Facts:

  • Enrolling PKU patients who have participated in a previous BMRN sponsored clinical study of PEG-PAL.
  • The study will last up to 5 years or until the drug is approved.

For additional information about the study, including details about participating centers, please see click here

4. A Phase II, Multi-center, Open-label, Dose-finding Study to Evaluate Safety, Efficacy and Tolerability of Subcutaneously (SC) Administered rAvPAL-PEG in Patients With PKU for 24 Weeks

This study is evaluating the safety, tolerability and effectiveness of multiple injections at different doses of an investigational drug to induce an early and sustained Phe reduction while decreasing the frequency and severity of hypersensitivity reactions in patients with PKU.

Key Study Facts:

  • Enrolling PKU patients between the ages of 16 and 70 years, inclusive.
  • Participants will receive up to 5 doses of study drug per week.
  • The initial study will last up to 24 weeks, and the participants will have the option to take part in an extension study.
  • The study will include people with PKU who have tried Kuvan® for at least 4 weeks, but are not currently taking it because their response was insufficient as determined by their physician.
  • The study will also include people with PKU who have tried Kuvan®, but abandoned it for reasons of non-compliance and have been off Kuvan® for at least 4 months.
  • Participants must be on stable diet with no changes for at least 4 weeks and be willing to maintain their current diet throughout the study.

For additional information about the study, including details about participating centers, please see click here

Completed Clinical Studies

Kuvan®

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels, please click here

A Phase 3, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet, please click here

GALNS-for-MPS-IVA-Morquio-A-Syndrome PEG-PAL for PKU BMN-701-IGF-GAA-for-Pompe-Disease BMN-673-PARP-Inhibitor-for-Genetically-Defined-Cancers