Uptravi is a prostacyclin receptor agonist that leads to vasodilation in the pulmonary circulation. It has been proven effective in the treatment of subsets of patients with PAH, including those with idiopathic and heritable PAH, PAH-associated with corrected simple congenital heart disease, and PAH-associated with connective tissue disorders. Uptravi is a therapy indicated in combination with phosphodiesterase type 5 (PDE-5) and/or endothelin receptor antagonist (ERA), or as monotherapy in patients that are not candidates for such therapies.
“Actelion has a comprehensive portfolio of treatments across the continuum of care in PAH that provide long-term outcome benefits,” said Dr. Jean-Paul Clozel, chief executive officer of Actelion, in a press release. “We are very pleased with today’s approval of Uptravi by the European Commission as it enables us to offer this outstanding oral medication, which provides long-term outcome benefits even for patients receiving background therapy, to PAH patients in Europe. We will now do our best to make Uptravi available to patients in the European Union as soon as possible.”
The authorization for marketing in the European Union was based on results from the GRIPHON Phase 3 clinical trial, a study designed to evaluate selexipag safety in PAH patients and to demonstrate the drug’s ability to prolong the time of first morbidity/mortality event when compared to placebo.
GRIPHON enrolled 1,156 patients with symptomatic PAH, 80 percent of which were receiving either ERA, a PDE-5 inhibitor, or a combination of both, who were randomized to a selexipag or placebo group. Patients in the treatment arm were first given 200 mg selexipag two times a day, and every week the drug dose was increased in 200 mg up to 1600 mg. If patients did not tolerate the new dose, treatment was reduced to the previously tolerated dose. Treatment duration was up to 4.2 years.
The trial revealed that the risk of developing PAH-related complications or death was decreased by 40 percent upon selexipag administration, compared to the placebo. The benefit was consistent in all patient sub-groups, including those taking ERA or PDE-5 inhibitor at baseline. Furthermore, the study established selexipag effectiveness, safety, and tolerability in PAH patients included in classes 2 to 3 of the World Health Organization (WHO) functional classification system.
“The approval of Uptravi is very positive news for the PAH community in Europe. With Uptravi, for the first time ever, we see a significant clinical benefit in combination with one and even two drugs targeting other treatment pathways. Together with its favorable tolerability profile, this makes Uptravi a treatment option that could truly change PAH care, for many patients,” said Nazzareno Galiè, head of the Pulmonary Hypertension Center at the Institute of Cardiology, University of Bologna.