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Kuvan fails to improve portal hypertension in patients with cirrhosis

Kuvan was not more effective in reducing portal pressure in patients with cirrhosis and portal hypertension than placebo, according to new study data.

Researchers randomly assigned 40 patients with cirrhosis and portal hypertension to receive 5 mg/kg per day of Kuvan (sapropterin dihydrochloride, BioMarin Pharmaceuticals; n = 19) for 2 weeks, with an increase to 10 mg at 8 days through 14 or 15 days, or placebo (n = 21). Randomization was based on concomitant treatment with beta-adrenergic blockers, according to the research. The researchers looked at splanchnic and systemic hemodynamics, endothelial dysfunction and oxidative stress markers, liver function tests and safety variables at baseline and post-treatment.

“The aim of this proof-of-concept randomized controlled trial was to evaluate the effects of continuous oral supplementation with sapropterin on the hepatic venous pressure gradient, systemic hemodynamics, tolerability, and safety in patients with cirrhosis and portal hypertension,” the researchers wrote.

Analyses showed that neither placebo nor sapropterin produced significant changes in

biochemical and hematologic parameters, except a small increase in platelet count in patients who received sapropterin. Bilirubin, albumin, prothrombin time and liver enzymes remained unchanged in both treatment arms.

In addition, neither sapropterin nor placebo changed the hepatic venous pressure gradient (HVPG; 16 ± 4.4 mm Hg at baseline vs. 15.8 ± 4.7 after sapropterin; P = .554 and 16 ± 4.6 mm Hg vs. 15.5 ± 4.9 mm Hg after placebo; P = .301).

Stratified analysis also did not show any differences in HVPG response to either placebo or sapropterin.

No serious adverse events were reported in either patient group. Also, no patients required dose adjustment or discontinued the use of sapropterin. Twenty percent of patients in the sapropterin group experienced mild or moderate adverse events, including flu-like symptoms, rhinorrhea and headache. However, all adverse events resolved by the end of the study and all patients were in good condition 1 month post-treatment, according to the research.

“Sapropterin, at the used dose, did not reduce portal pressure in patients with cirrhosis,” the researchers concluded. “To better clarify the potential role of [tetrahydrobiopterin] in cirrhosis, future strategies should aim at improving [tetrahydrobiopterin] bioavailability rather than increasing the total amount of [tetrahydrobiopterin] or biopterins.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.