Latest Research

KUVAN™ (sapropterin dihydrochloride) Tablets clinical trial study results

In December 2007, the US Food and Drug Administration (FDA) approved KUVAN for the treatment of PKU. KUVAN 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.

In two randomized, placebo-controlled and two open-label, uncontrolled clinical trials of a total of 747 patients with BH4-responsive PKU, KUVAN was shown to reduce blood Phe levels and demonstrated a favorable safety profile.

Learn more about KUVAN.

Somatic gene therapy for PKU

It has become possible to test various gene transfer vehicles with available animal models. However, unexpected results have occurred. Liver PAH gene transfer both in vivo and in vitro, as well as autologous nonhepatic gene-targeting attempts, have failed due to poor efficacy of gene delivery and/or lack of essential cofactor BH4. These approaches do not appear promising unless an appropriate gene transfer vector is devised.⁶⁸

Phenylalanine ammonia lyase

The enzyme phenylalanine ammonia lyase breaks down Phe in the gastrointestinal tract, where Phe is converted into a nontoxic derivative, trans-cinnamic acid.⁶⁹ Both intraperitoneal phenylalanine ammonia lyase injection and oral administration of the enzyme lowered plasma Phe concentrations in the PAH^enu2 mouse.⁷⁰

Supplementation with large neutral amino acids

There is an approach to preventing the influx of Phe to the brain by the addition of large neutral amino acids (valine, isoleucine, and leucine) to the diet. This supplementation reduces the toxic effects of Phe on the central nervous system. In the PAH^enu2 mouse, this supplementation led to a significant reduction of blood and brain Phe concentrations.¹⁹ Supplementation with valine, isoleucine, and leucine in patients with PKU was associated with a significant reduction of the cerebrospinal fluid-serum ratio of Phe and with a small improvement in neuropsychological test performance.^71,72 Daily treatment with valine, isoleucine, and leucine may help patients who are unable to maintain low blood Phe levels and should be considered an alternative strategy to treat PKU.⁷² Clinical trial results remain preliminary at this time.

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 for KUVAN

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.