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New Mutation Identified in Pulmonary Arterial HTN
Two additional studies show improved exercise capacity with riociguat in pulmonary HTN

WEDNESDAY, July 24 (HealthDay News) -- A new mutation has been identified in pulmonary arterial hypertension, and riociguat appears to be beneficial in treating the condition, according to three studies published in the July 25 issue of the New England Journal of Medicine.

Lijiang Ma, M.D., Ph.D., from the Columbia University Medical Center in New York City, and colleagues conducted whole-exome sequencing in three family members with pulmonary arterial hypertension without mutations in genes known to be associated with the disease. The researchers identified a novel heterozygous missense variant in KCNK3, which was a candidate disease-causing gene. Additional variants were identified in KCNK3 in 92 unrelated patients with familial pulmonary hypertension and in 230 patients with idiopathic arterial hypertension.

Hossein-Ardeschir Ghofrani, M.D., from the University of Giessen and Marburg Lung Center in Germany, and colleagues conducted a phase 3, double-blind study involving 443 patients with symptomatic pulmonary arterial hypertension who were randomized to receive placebo or riociguat (up to 2.5 mg three times daily or up to 1.5 mg three times daily). By week 12, the researchers found that the six-minute walk distance increased in the 2.5 mg-maximum riociguat group and decreased in the placebo group. In a third study, Ghofrani and colleagues found that riociguat correlated with improved exercise capacity at 16 weeks in a phase 3, randomized, controlled trial involving 261 patients with inoperable chronic thromboembolic pulmonary hypertension or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy.

"Riociguat appears to be safe and is a promising addition to the pharmacopeia for Group 1 pulmonary hypertension and potentially the first effective oral therapy for inoperable Group 4," writes the author of an accompanying editorial.

The second and third studies were funded by Bayer Healthcare, the manufacturer of riociguat.

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