Selexipag improved the condition of Japanese with pulmonary arterial hypertension (PAH), according to a clinical trial.
The United States and a number of other countries have approved the therapy, but Japan wanted a clinical trial specifically with Japanese patients before authorizing it. Selexipag is available in the U.S. under the brand name Uptravi, and is marketed by Actelion Pharmaceuticals.
The study, “Efficacy And Safety Of An Orally Administered Selective Prostacyclin Receptor Agonist, Selexipag, In Japanese Patients With Pulmonary Arterial Hypertension,” was published in the Circulation Journal.
Selexipag is an oral activator of the prostacyclin receptor. When the receptor is activated, it triggers vasodilation, or widening of blood vessels, to lower blood pressure.
The GRIPHON clinical trial (NCT01106014) tested the treatment in patients from 39 countries. The results led to approvals in most.
Because Japanese patients did not participate in the study, researchers started a Phase 2 trial to investigate the effectiveness and safety of selexipag in this population.
Researchers administered selexipag at increasing doses to 37 Japanese participants. The starting dose was 200 μg twice daily, increasing up to 1,600 μg.
After 16 weeks, 33 patients experienced a decrease in pulmonary vascular resistance, meeting the study’s primary objective. Those whose condition improved included patients who had already received other treatments, such as a phosphodiesterase inhibitor and endothelin receptor antagonist.
Selexipag also improved patients’ exercise capacity, based on a six-minute walk test. Patients were able to walk 459 meters after treatment, versus 445 before.
In addition, selexipag led to improvements in four, or 12%, of patients’ disease, as measured on the World Health Organization scale of patients’ ability to function. The other 29 patients, or 88%, maintained their scores.
The treatment was well-tolerated, even if selexipag was administered on top of other PAH medications. The most commonly reported adverse events were headache, 73 percent; diarrhea, 45.9 percent; jaw pain, 45.9 percent; nausea, 37.8 percent; and flushing, 32.4 percent.
“In this trial, selexipag was well tolerated and showed an acceptable safety profile in addition to significant improvement in pulmonary hemodynamics, exercise tolerance, and symptoms,” the researchers wrote. “Selexipag could be a useful treatment option for Japanese PAH patients.”
The United States has approved selexipag for idiopathic PAH, heritable PAH, PAH associated with connective tissue disease, PAH associated with congenital heart disease with repaired shunts, and PAH associated with drugs and toxins. It can be used to treat patients with WHO functional class II, III or IV symptoms.