Riociguat Shows Promise in Pulmonary Hypertension


Source: American Thoracic Society

By Ed Susman, Contributing Writer, MedPage TodayPublished: May 22, 2013Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

PHILADELPHIA -- The investigative agent riociguat increased distance walked by patients diagnosed with pulmonary arterial hypertension, researchers reported here.
In patients who had never been treated with either endothelin receptor antagonists or non-intravenous prostanoids, 3 months on riociguat enabled them to walk an additional placebo-corrected 38 meters [95% CI 16-60] in the 6-minute walk test, and those who were pre-treated with these other agents were able to add placebo-corrected 34 meters [95% CI 11-56] to their walking distance, said Marc Humbert, MD, vice chairman of the National Reference Centre for Pulmonary Hypertension, at Universitaire Paris-Sud in Paris.

"Riociguat was consistent when administered in treatment-naive patients and when given in combination with endothelin receptor antagonists and prostanoids," Humbert said in his oral presentation at the annual international conference of the American Thoracic Society.
Riociguat (BAY 63-2521) is the first drug in a class of stimulators of soluble guanylate cyclase and is believed to improve systemic arterial oxygenation.

Humbert demonstrated that treatment with the new drug was consistent in the walking, the primary endpoint, and also in several secondary endpoints, including pulmonary vascular resistance, improving level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), World Health Organization functional class, and the time to clinical worsening.
"Riociguat was well tolerated in treatment-naive and pretreated patients," Humbert said in his presentation at the meeting, attended overall by more than 14,000 clinicians and allied healthcare professionals.

The most frequent adverse events among the 123 treatment-naive patients were headache, dyspepsia and peripheral edema. They were also the most frequent adverse events among the 131 patients who had been pretreated with other therapies to control pulmonary arterial hypertension. Mild and moderate hypotension was observed among 14 patients in the treatment-naive group and in 10 patients who had other treatments prior to entering the study. Only one patient -- in the treatment experienced group -- had severe hypotension, Humbert reported.

The patients in the studies were about 48 years of age in the treatment-naive group and about 52 years of age in the treatment experienced group. More than 75% of the patients were women. At baseline, the patients in both groups were able to walk about 360 meters in the 6-minute walking distance test.
Humbert said the research team looked at subgroups in the PATENT-1 study to determine if outcomes differed when it came to treatment status. "Patients with pulmonary arterial hypertension pretreated with drugs specific for the disease may be less responsive to add-on therapy compared to treatment-naive patients," he said.

"This is a very promising and exciting drug because it has a different mechanism of action," said Akaya Smith, MD, assistant professor of clinical medicine at the University of Pennsylvania, Philadelphia. She told MedPage Today that the short-term study showed modest improvements, but similar to what has been seen with other drugs.
"We don't know yet where riociguat will fit into treatment," she said. "It may be used as a stand-alone drug or as an add-on therapy." Further studies and/or clinical practice will determine that, she suggested.

Humbert disclosed commercial relationships with Actelion, Aires, Bayer, GlaxoSmithKline, Lilly, Novartis, Pfizer, and United Therapeutics.
Smith disclosed commercial relationships with Gilead.
Primary source: American Thoracic Society Source reference:Humbert M, et al "Efficacy of riociguat in pretreated versus treatment-naïve patients with pulmonary arterial hypertension (PAH) in the phase III PATENT-1 study" Am J Respir Crit Care Med 2013: A3534.

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