Expanded Access Program for Sapropterin Begins Nationwide
By Alexander Porter, MD, Medical Services, BioMarin Pharmaceutical Inc., Novato, CA
From the Fall 2007 issue of National PKU News.
June marked the beginning of a nationwide Expanded Access Program (EAP) for sapropterin
dihydrochloride, or sapropterin, an investigational treatment for PKU.
If approved by the U.S. Food and Drug Administration (FDA), the brand name for this
treatment is expected to be Kuvan™. Under an Expanded Access Program, this one through BioMarin,
the FDA allows a drug development company, under certain circumstances, to provide early access
to drugs that are being developed to treat serious diseases but have not yet been approved for prescribed use.
More than 50 metabolic centers across the country have enrolled in the EAP and will
offer sapropterin to patients who qualify.
The first center to take part in the program is Children’s Memorial Hospital in Chicago,
under the direction of Dr. Barbara Burton, Director of the PKU Program and Professor of
Pediatrics at Northwestern University’s Feinberg School of Medicine.
“We are pleased to be able to provide sapropterin through the EAP, and look forward
to its availability, if approved by the FDA, as a treatment option for PKU,” said Dr. Burton.
“We now know that managing PKU entirely through diet may not produce optimal mental and neurological
results for all patients. While dietary restrictions can be effective in lowering phe levels,
the diet does not have the ability to remedy the underlying enzymatic defect that exists in
individuals with PKU. With sapropterin, the PAH enzyme is stimulated so that it can metabolize phe to
tyrosine, and in clinical studies, this has shown to lower blood phe levels and increase phe
tolerance in some patients with PKU,” said Dr. Burton.
As we all know, currently the only way to lower blood phe levels is through a phe-restricted diet,
which can be difficult to follow.
Sapropterin, if approved by the FDA, will be the first FDA-approved prescription drug to treat PKU by
lowering phe levels and increasing phe tolerance. It is not possible to predict if a patient will
respond to sapropterin before taking it; nor can a physician predict how the addition of the drug
may affect an individual’s diet. However, BioMarin’s clinical studies with sapropterin have shown
encouraging results in many PKU patients with varying levels of disease severity.
“While diet will continue to play an important role in the management of PKU, sapropterin may
offer physicians and dieticians a critically-needed treatment option for improving the care and
health of PKU patients,” added Dr. Burton.
Through the EAP, sapropterin will be provided at no cost to eligible patients. If sapropterin
receives marketing approval from the FDA, patients participating in the EAP will need to transition
the cost of their treatment to their own health insurance within two months.
Who Can Participate?
PKU patients who are older than 8 years of age, not enrolled in a clinical trial for sapropterin, and meet all inclusion criteria as stated in the EAP protocol, are eligible to participate. Patients with mild, moderate, and classic PKU may be eligible for enrollment in the EAP.
For More Information
People who are interested in participating in the EAP should consult their physician, who can determine eligibility.Physicians can obtain more information or request enrollment materials for the EAP through a toll-free number and e-mail address: 1-877-811-7327 or PKU-SEAP@registrat.com.
More Information on the Expanded Access Program
A conversation with Dr. Alex Porter, Medical Affairs Director for BioMarin Pharmaceutical Inc.PKU News: How does sapropterin work?
Dr. Porter: Sapropterin is a pharmaceutical formulation of tetrahydrobiopterin (BH4), the natural cofactor for phenyalanine hydroxylase (PAH), the enzyme that is defective in PKU. Sapropterin has been shown to stimulate the PAH enzyme in some PKU patients, so that it metabolizes some phe to tyrosine.
PKU News: What is BH4 response? Will everyone with PKU respond to sapropterin?
Dr. Porter: BH4 response refers to whether or not a person with PKU can benefit from taking BH4. Doctors measure the response by checking if blood phe levels drop significantly while the phe-restricted diet is held constant. Sapropterin, a formulation of BH4, will not work for everyone, but studies have shown that some patients with mild, moderate, and “classic” PKU have responded.
Due to the genetic variability in people with PKU, it is not possible to predict whether sapropterin will be effective until the drug is taken for a period of time. To determine responsiveness, patients must take the drug under the supervision of a health care provider.
PKU News: At what age can PKU patients begin to take sapropterin?
Dr. Porter: In the EAP, patients 8 years of age and older are eligible for possible participation. To-date, we have studied patients 4 years of age and older in our clinical trials.
PKU News: Will some patients be able to eliminate formula and/or eat an entirely unrestricted diet with sapropterin?
Dr. Porter: The increase in phe tolerance will vary. Of patients who responded in our clinical trial, phe tolerance, on average, was doubled. Some patients may be able to reduce or eliminate formula and consume more natural protein while maintaining phe control. It is very important that people who use sapropterin continue to work closely with their physician and dietitian to establish the ideal diet that accommodates their individual phe tolerance.
PKU News: Does the drug have side effects?
Dr. Porter: In our clinical studies, the type and frequency of adverse events, or side effects, observed in studies with sapropterin were similar to those seen in patients receiving a placebo (a sugar pill containing no active BH4).
Most reported side effects were mild and temporary and mainly consisted of headache, diarrhea, abdominal pain, upper respiratory tract infections, and throat pain. In our studies, side effects resolved without having to stop taking sapropterin.
PKU News: Will sapropterin continue to work indefinitely?
Dr. Porter: In clinical trials, the benefit of sapropterin continued throughout the length of the longest study period (26 weeks). No loss of benefit has been observed in patients taking the drug.
PKU News: How much sapropterin is needed and how often?
Dr. Porter: The “starting dose” is 20 mg/kg/day. Each tablet contains 100 mg of sapropterin. During the EAP, a patient’s blood phe levels will be monitored by his/her doctor to determine the correct dosage for the patient.
Example: A child weighing 60 lbs (27 kg) would take 5 or 6 tablets/day at the starting dose of 20 mg/kg/day; an adult who weighs 150 lbs (68 kg) would take 13 or 14 tablets/day at the starting dose. The doctor will determine the exact number of daily tablets.
Sapropterin is taken once a day. Patients can swallow the tablets or they can dissolve them in water or apple juice before taking them.
PKU News: When will the FDA make a decision about sapropterin?
Dr. Porter: A new drug application for sapropterin was submitted by BioMarin Pharmaceutical Inc. to the FDA in May 2007; the FDA could make their ruling before the end of 2007.
If the drug is approved, it is expected to be called Kuvan.
Last update: February 2008
National PKU News: www.pkunews.org
E-mail: schuett@pkunews.org