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Questions and Answers on Sapropterin (Kuvan)
1. What is Kuvan and in what form is it available?
Kuvan is sapropterin dihydrochloride, a synthetic form of a naturally occurring substance tetrahydrobiopterin (BH4). Kuvan is provided as 100 mg tablets that are to be dissolved in water or apple juice, and then taken within 15 minutes after they have been dissolved.
2. What is tetrahydrobiopterin (BH4)-responsive Phenylketonuria (PKU)?
Phenylketonuria (PKU) is an inherited disorder, in which the activity of the enzyme phenylalanine hydroxylase (PAH) is deficient. PAH helps break down phenylalanine (Phe) in the body. Phenylalanine is an amino acid that is obtained from food. Patients with PKU cannot break down Phe properly, which results in high levels of Phe in the blood. In infants and children, high blood Phe levels over time can result in mental retardation, smaller brain size, delayed speech, and other neurologic problems. In adolescents and adults, high blood Phe levels can result in problems with concentration and attention.
Patients with PKU have a large variety of changes to the PAH enzyme, so not all patients with PKU will respond to BH4. In clinical trials of patients with PKU, only 20% to 56% of these patients responded to treatment with Kuvan (called BH4-responsive PKU). Response to Kuvan was measured by the lowering of blood Phe levels with Kuvan treatment.
3. How prevalent is it in American society?
One in 12,000 to 15,000 infants in the United States is born with PKU.
4. Which race or ethnic group is it seen most in?
In the United States, PKU is more common in Caucasians (approximately 1 in 8,000 babies), and is less common, for example, in African Americans (approximately 1 in 50,000).
5. How do you know if your newborn or child has the disease?
All states in the United States perform newborn screening testing for PKU at birth. You will be notified if your child’s screening test for PKU is positive.
6. Are parents carriers of this genetic disorder?
Yes. Children must inherit one copy of the defective gene for PKU from each parent. Children only show signs of PKU if they inherit a defective copy from each parent.
7. What goes wrong to cause this disease? Does lack of prenatal care cause it?
PKU is an inherited disease, where both copies of the gene must be defective to show signs of the disease. People cannot “develop” PKU later in life; they must be born with it. Lack of prenatal care has no effect on having PKU.
8. Is Kuvan the only treatment for PKU disease?
No. All patients with PKU must be treated with a low-Phe diet, and most patients will also be treated with low-Phe medical foods and formulas. For all patients, monitoring of blood Phe levels must be performed regularly by medical specialists familiar with the treatment of PKU. Patients who are taking Kuvan still need to be managed with a low-Phe diet, and have regular monitoring of their blood Phe levels.
9. How does Kuvan work?
Kuvan is a synthetic form of BH4. BH4 is a cofactor for the enzyme PAH. The enzyme PAH cannot function properly without BH4. In some patients with PKU, giving BH4 as Kuvan increases the activity of the enzyme PAH. Not all patients with PKU will respond to Kuvan. The only way to know if a patient will respond is to Kuvan is to give the patient Kuvan and monitor his/her blood Phe levels.
10. Why must you be on a restricted diet?
High levels of Phe in the diet can over-ride the effects of Kuvan on blood Phe levels. All patients taking Kuvan must continue to follow a Phe-restricted diet and have their blood Phe levels monitored by medical personnel trained in the management of PKU.
11. What types of foods should you avoid? How does one distinguish between a food that is high, low or absent of phenylalanine?
Phenylalanine is present in foods that contain proteins, such as meats, dairy, and eggs. All patients with PKU should be working with a dietician knowledgeable about PKU to help control their diet.
12. What are the symptoms of this disease?
PKU is diagnosed by special medical blood testing, and by newborn screening testing at birth. The signs and symptoms of PKU develop over time after high blood Phe levels have been present for weeks to months, or longer. In infants and children, high blood Phe levels over time can result in mental retardation, smaller brain size, delayed speech, and other neurologic problems. In adolescents and adults, high blood Phe levels can results in problems with concentration and attention.
13. Can PKU’s effects be reversed by Kuvan and a regulated diet?
No. Once neurologic problems, such as mental retardation, have developed, they cannot be reversed by Kuvan or a regulated diet. The goal of treatment with Kuvan and diet is to prevent neurologic problems from developing.
14. Why is BioMarin establishing a general disease registry for PKU? What is the purpose of it?
PKU is a rare disease, and only a small number of people in the United States (and the world) have it. The purpose of the registry is to provide a way for physicians, the FDA, and BioMarin to monitor the safety and effectiveness of Kuvan over a long period of time in as many patients as possible.
15. Why is it important to check your Phe levels in your blood?
The complications of PKU are a result of high blood Phe levels over time (for example, weeks to months, or longer). It has been shown in clinical studies conducted in patients with PKU that keeping blood Phe levels at recommended levels decreases the neurologic problems that can develop with PKU. Neither Kuvan nor following a low-Phe diet can cure PKU, but PKU can be managed. Therefore, monitoring of blood Phe levels and a low-Phe diet will need to occur over the life of the patient.
16. Can someone die from PKU disease?
Yes, but this would be due to the severe neurologic complications of PKU that develop over long periods of time. More typically, neurologic problems, such as lowered intelligence, can develop with PKU.
17. How will this drug therapy alter the quality of a PKU patients’ life?
It is hoped that the lowering of blood Phe levels in with patients BH4-responsive PKU would result in fewer neurologic complications of PKU over time, and that patients with BH4-responsive PKU who are taking Kuvan would have an easier time controlling their blood Phe levels. However, long-term studies of neurologic development have not been done with Kuvan.
18. What are the side effects of Kuvan?
The most common side effects of Kuvan were headache, vomiting, diarrhea, runny nose, cough, and sore throat. Most of these side effects were mild, and did not result in patients stopping Kuvan treatment.
19. How often should I see a doctor if I am on Kuvan and what type of doctor should I see for my PKU disease?
All patients with PKU should be treated by a medical doctor knowledgeable in the treatment of PKU, such as a Medical Geneticist. Your pediatrician or regular doctor can refer you to a specialist. Your specialist will determine how often you will need to be seen.
Approved labeling for Kuvan 
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Date created: December 13, 2007
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