Since the discovery of PKU as a distinct disease in 1934, scientific interest in the disease has advanced at an incredible pace, going from obscurity to the forefront of cutting-edge biotechnology research. In 1958, the Guthrie test was the first affordable test for screening hyperphenylalaninemia in newborns. Its simplicity and cost-effectiveness led to its standard use for newborn screening in American hospitals by 1966. Scientists later discovered that mutations in the PAH gene result in a defective PAH enzyme activity and an inability to convert Phe to tyrosine.2 Tetrahydrobiopterin (BH4) was revealed to be the cofactor for the PAH enzyme.3

This section will go into more details about the biochemistry of PKU and the impact of elevated Phe levels on the cognitive and psychological profiles of PKU patients.

Read more about PKU:

  • Biochemistry
    In PKU, the underlying defect in the phenylalanine hydroxylase (PAH) enzyme interrupts Phe metabolism, creating elevations in blood Phe levels that can result in brain toxicity4
  • Impact of Elevated Phe
    Even small increases in elevated blood Phe levels can impact patients and are shown to be associated with declines in brain function5
  • Noncompliance With Diet
    Elevated Phe due to dietary noncompliance is common, and the percentage of managed patients with Phe levels above target range is high6,7
  • Cognitive Problems
    Many PKU patients are still at risk for cognitive problems, with both elevated Phe and the stability of blood Phe levels shown to affect overall cognitive function8-13
  • Psychological Problems
    PKU patients may still be at risk for psychological problems, including more attentional problems leading to increased stimulant use14,15

Long-term studies of neurocognitive outcomes with KUVAN treatment have not been conducted. BioMarin is implementing a trial to evaluate long-term neurocognitive outcomes in PKU patients treated with KUVAN.

Indication

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

Important Safety Information

Prolonged exposure to elevated blood Phe levels in PKU patients can result in severe neurologic damage. The initiation of KUVAN therapy does not eliminate the need for careful monitoring of blood Phe levels and ongoing dietary management.

Some patients receiving KUVAN can experience significant drops in blood Phe levels. Patients should be monitored closely to ensure that blood Phe levels do not fall too low.

Not all patients with PKU respond to treatment with KUVAN. Response to treatment can only be determined by a therapeutic trial of KUVAN.

KUVAN has not been studied in patients with liver or renal impairment. Patients who have these conditions should be carefully monitored when receiving KUVAN. Caution should be used with the administration of KUVAN to patients who are receiving levodopa and drugs that affect nitric oxide–mediated vasorelaxation or folate metabolism.

The most serious adverse reactions reported during KUVAN administration (regardless of relationship to treatment) were gastritis, spinal cord injury, streptococcal infection, testicular carcinoma, and urinary tract infection. Mild to moderate neutropenia was also noted. The most common adverse reactions were headache, diarrhea, abdominal pain, upper respiratory tract infection, pharyngolaryngeal pain, vomiting, and nausea.

Please read the full Prescribing Information by clicking here.

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