New Treatments for
PKU
Barbara K. Burton, MD
Director, PKU Clinic
Children’s Memorial Hospital
Chicago, IL
New Developments in
the Treatment of PKU
• Kuvan
• PEG-PAL
• Home blood phe monitor
What is Kuvan®?
• The first FDA-approved drug for
treatment of PKU.
• The generic name is
sapropterin. It is a synthetic
form of 6R- BH4 or
tetrahydrobiopterin, the
cofactor in the PAH reaction.
Simplified biochemistry of
phenylalanine metabolism
PAH Enzyme
Phenylalanine
Tyrosine
BH4
Cofactor
PAH = phenylalanine hydroxylase
BH4 = cofactor tetrahydrobiopterin
What does Kuvan do?
• It activates the body’s own PAH
enzyme to break down more phe
• It lowers phe levels
• However, it only works for 40-50% of
patients with PKU. The only way to
determine if it will work for you is to
try it.
How Can you Tell if Kuvan
Will Work for You?
• Start taking the medication once a day – dose is
determined by body weight
• Obtain blood phe tests just before starting the
medication and several times more in the next
several weeks. Keep diet consistent during this
time.
• If medication works, there should be a decline in
the blood phe level. For patients on diet with very
low blood phe levels at baseline, it may be
necessary to add phe to the diet to see if phe
tolerance can be increased.
Improved Control of Blood Phe Level
in a Patient on Kuvan
• Patient 1 is a now 32 year old man who has been on
Kuvan for over three years,
• He was new to our clinic, stating that he had been off
dietary treatment for PKU since early childhood.
• His initial blood phe level was 1010 umol/L (16-17
mg/dl). He complained of many neuropsychiatric
symptoms attributable to his PKU. He was
intermittently employed.
• He wanted treatment for his PKU and was willing to
attempt dietary therapy but, based on previous
attempts, felt it would be very difficult. He was started
on Kuvan.
Improved Control of Blood Phe Level in a
Patient on Kuvan
• Patient 1 — Mean blood phe on treatment with Kuvan
has been 369 umol/L
• He has had resolution of many of the symptoms of his
PKU.
• Reports decreased anxiety, depression, phobias,
improved mental clarity and attention span.
• Finished a community college training program and
has secured fulltime employment.
• Is able to concentrate long enough to read a book,
something he was unable to do previously.
Increase in Natural Protein Intake In A
Well-Controlled Patient With Mild PKU
• Patient 2 is an 18 year old college junior
who has been on Kuvan for two years.
• He has mild PKU which was always wellcontrolled. Prior to taking Kuvan, his phe
levels were in the target range. His diet
prescription included 1000 mg phe from
food; 70 grams protein from formula
(combination of Phenex 2 and PKU
Coolers)
Increase in Natural Protein Intake In A
Well-Controlled Patient With Mild PKU
• Post Kuvan, the patient’s plasma phe
levels remain within the target range
(below 360 umol/L).
• He eats essentially a normal diet,
including meat.
The “Typical” BH4 Responsive
Patient on Treatment
• 5 year old boy; mild to
moderate PKU
• Phe prescription prior
to starting Kuvan was
450 mg/day
• Was increased to 1300
mg/day (300%); now
counts protein grams
(26g/day). No longer
eats low protein foods
What are the Side Effects
of Kuvan?
• No serious side effects were
identified in the clinical trials
• GI side effects occur in a small
fraction of patients. These can
largely be avoided by taking
medication with food or
formula.
What is PEG-PAL
• PAL is an enzyme normally present
only in plants, bacteria and yeast - it
breaks down phe in a way that does
not involve PAH
• The enzyme, PAL, is bound to
polyethylene glycol (PEG) to prevent
the body’s immune system from
recognizing it as “foreign” and
attacking it with antibodies
PEG-PAL is an Investigational
Drug
• Animal studies showed it was
effective in controlling blood phe
levels in the PKU mouse
• Phase 1 clinical trial has been
completed in PKU patients
• Phase 2 clinical trial is currently in
progress
How Does PEG-PAL Differ
from Kuvan
• PEG-PAL should theoretically work
for all patients with PKU
• It is an injection
• Since it is a foreign protein, some
side effects due to allergic reactions
would not be unexpected
The Blood Phe Monitoring
System
•Will be similar in concept to
home glucose monitors
•Designed for use at home and in
the clinic
BPMS Device Operation
1.
Insert disposable test
strip into meter,
meter automatically
turns on
2.
Prick finger with
lancet
3.
Apply small drop of
blood to test strip
4.
Less than 1 minute
later, Phe
measurement
automatically
displays on screen
Benefits of Home Phe
Monitor
• Will allow more frequent blood
phe measurements, which will
improve metabolic control
• Immediate test results
• Less blood needed so
fingerstick less painful
New Treatments for PKU Summary
• We now have multiple options
for controlling blood phe and
promoting optimal outcome in
PKU
• For PKU patients and their
families, the future is very
bright