History of PKU (Phenylketonuria)

It has been less than 100 years since a Norwegian doctor first identified PKU as a specific disease. Since then, giant steps have been made in understanding and treating PKU.10

Here are a few highlights:

PKU discovered: 1934

In 1934, a doctor in Norway named Asbjorn Folling noticed that several mentally retarded patients had a strange odor. He figured out that it was from something called "phenylacetic acid." The patients' urine also had a very high level of a chemical called "phenylketone." That is how the disease got its name, phenylketon-uria.

Folling also thought the disease was most likely inherited, and was the first to suggest using diet to manage it.10

The Child Who Never Grew: 1950

Pearl Buck, best known for her Pulitzer-Prize winning The Good Earth, delighted in the birth of her daughter Carol in 1920, and was heartbroken when she failed to develop normally. Buck was unable to discover what was wrong with Carol, who grew up mentally retarded as a result of PKU. She published The Child Who Never Grew in 1950 with the hope that her experience could help others.11

First supplement: 1951

In 1951, a German professor, Horst Bickel, developed the first PKU formula. The unflavored protein drink provided many amino acids without Phe. For the first time, PKU patients could get most of the nutrition they needed while keeping Phe levels low.

Simple test developed: 1958

Robert Guthrie developed a way to test for high Phe in newborns using a drop of blood. The test was fast, simple and inexpensive, unlike earlier tests.10

PKU newborn screening: 1966

In 1966, hospitals across the country started using the Guthrie test to screen all infants for PKU. By identifying newborns with PKU at birth and managing care from the beginning, mental retardation could at last be avoided.

First drug therapy for PKU: 2007

KUVAN® (sapropterin dihydrochloride) Tablets became the first medicine approved for PKU.

Indication and Fair Balance statements for Consumers

KUVAN® (sapropterin dihydrochloride) Tablets is approved to reduce blood Phe levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). KUVAN is to be used with a Phe-restricted diet.

Important Safety Information

High blood Phe levels are toxic to the brain and can lead to lower intelligence and decrease in the ability to focus, remember and organize information. Any change you make to your diet may impact your blood Phe level. Follow your doctor’s instructions carefully. Your doctor and dietitian will continue to monitor your diet and blood Phe levels throughout your treatment with KUVAN.

If you have a fever, or if you are sick, your Phe level may go up. Tell your doctor and dietitian as soon as possible so they can see if they have to adjust your treatment to help keep your blood Phe levels in the desired range.

KUVAN is a prescription medicine and should not be taken by people who are allergic to any of its ingredients. Tell your doctor if you have ever had liver or kidney problems, are nursing or pregnant or may become pregnant, have poor nutrition or are anorexic. Your doctor will decide if KUVAN is right for you. Tell your doctor about all the medicines you take.

The most common side effects reported when using KUVAN are headache, diarrhea, abdominal pain, upper respiratory tract infection (like a cold), throat pain, vomiting, and nausea.

To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full prescribing information at www.kuvan.com.