Actelion’s Uptravi for PAH Granted Marketing Authorization by European Commission

Actelion’s Uptravi for PAH Granted Marketing Authorization by European Commission

The European Commission recently granted marketing authorization in the EU for Switzerland-based Actelion’s product Uptravi (selexipag) for the treatment of pulmonary arterial hypertension. PAH is a life-threatening disease characterized by abnormal constriction of the pulmonary artery, forcing the heart to work faster and elevating blood pressure in arteries within the lungs, potentially leading to heart failure.

Originally discovered by Nippon Shinyaku, a research and development company in Japan, selexipag selectively targets prostacyclin receptors on vascular smooth muscle cells. By binding to the prostacyclin receptor, the drug induces a vasodilation response in blood vessels. Selexipag is indicated for the long-term treatment of adult patients with PAH (WHO functional class II-III), either alone or in combination with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor.

The EU label for Uptravi was in part based on data from the GRIPHON Phase 3 clinical trial, which demonstrated the effectiveness, safety, and tolerability of Uptravi in PAH patients with WHO FC II-III. The trial included 1,156 PAH patients between the ages of 18 and 75 — the largest trial conducted in PAH. Patients were randomly distributed in the selexipag group (574 patients) and the placebo group (582 patients).

Results showed that selexipag was able to significantly decrease the risk of morbidity/morbility events, a primary endpoint, by 40 percent when compared to the control (placebo) group.

“For many years we have known that the prostacyclin pathway can be key in treating PAH, yet due to the route of administration of the existing therapies being so burdensome, the pathway has been largely underused, with only about 20 percent of patients ever receiving a prostacyclin at some point during their PAH treatment,” said Prof. Sean Gaine, consultant respiratory physician at Mater Misericordiae Hospital Dublin, in a press release.

“Uptravi, as an innovative oral treatment that is supported by long-term outcome results, now allows us to offer combination therapy regimens that target all three established treatment pathways,” he said.

Prof. Nazzareno Galiè, head of the Pulmonary Hypertension Center at the Institute of Cardiology at the University of Bologna, said 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,” Galiè added.

In term of safety profile, selexipag was evaluated in the 1,156 patients with symptomatic PAH who were treated with the drug for up to 4.2 years. The most commonly observed adverse events related to Uptravi treatment included diarrhea, arthralgia, headache, myalgia, vomiting, nausea, jaw pain, pain in extremities, and flushing.

“Actelion has a comprehensive portfolio of treatments across the continuum of care in PAH that provide long-term outcome benefits,” said Actelion CEO Jean-Paul Clozel, M.D. “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.”


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