OREANDA-NEWS. Actelion today announced the commercial availability of the oral, selective, IP prostacyclin receptor agonist, Uptravi® (selexipag) for the treatment of pulmonary arterial hypertension (PAH) in Germany.

Uptravi is indicated for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class (FC) II-III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as mono therapy in patients who are not candidates for these therapies. Efficacy has been shown in a PAH population including idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease. [1]

The EU label for Uptravi (originally discovered and synthesized by Nippon Shinyaku) was based in part on the Phase III GRIPHON study, whose main findings were published in the New England Journal of Medicine in December 2015. This placebo-controlled study, the largest ever in PAH, established the effectiveness, safety and tolerability of selexipag in PAH patients with WHO Functional Class II-III, showing that selexipag was able to reduce the risk of a morbidity/mortality event by 40%. [2]

Professor H. Ardeschir Ghofrani, University Hospital Giessen, Germany, commented: "Uptravi offers an oral therapy that effectively targets the prostacyclin pathway and significantly delays the progression of pulmonary arterial hypertension. It is supported by robust outcome-based evidence in combination with an ERA, or a PDE-5 inhibitor, and even in combination with both an ERA and a PDE-5 inhibitor. This opens the way for more oral combination treatments early on in the progression of the disease, with proven long-term outcome benefits for more patients."

Michael Danzl, General Manager of Actelion Germany, commented: "The availability of Uptravi is a milestone for PAH patients in Germany, where until now, the options for treatments targeting the prostacyclin pathway have been limited, and were burdensome for the patients. With Uptravi, there is now an oral option in all three established treatment pathways."

Hans Dieter Kulla, President of pulmonale hypertonie e.v., added: "This new product launch is a major step in terms of achieving the best possible care for patients living with PAH in Germany. We hope Uptravi can further impact the long-term outcome for many patients, which ultimately also helps their families and caregivers."

The safety of Uptravi has been evaluated in a long-term, placebo-controlled study enrolling 1,156 patients with symptomatic PAH (GRIPHON study). The exposure to Uptravi in this trial was up to 4.2 years with median duration of exposure of 1.4 years. Adverse reactions occurring more frequently on Uptravi compared to placebo - greater than or equal to 3% - over the course of the study, were headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, flushing, arthralgia, anemia, decreased appetite and rash. These adverse reactions are more frequent during the dose titration phase. Hyperthyroidism was observed in 1% (n=8) of patients on Uptravi and in none of the patients on placebo.

Uptravi is available in the following strengths: 200 mcg [Light yellow tablet debossed with 2], 400 mcg [Red tablet debossed with 4], 600 mcg [Light violet tablet debossed with 6], 800 mcg [Green tablet debossed with 8], 1000 mcg [Orange tablet debossed with 10], 1200 mcg [Dark violet tablet debossed with 12], 1400 mcg [Dark yellow tablet debossed with 14], 1600 mcg [Brown tablet debossed with 16].

ABOUT H. ARDESCHIR GHOFRANI

H. Ardeschir Ghofrani, MD, received his medical degree from the Medical School at Giessen University in Germany. He is Professor of Internal Medicine at University Hospital Giessen and Marburg. He is currently Head of the Pulmonary Hypertension Division, Department of Internal Medicine, at Giessen. He also leads a collaborative group on cardiopulmonary vascular system research. He is a steering committee member of the Excellence Cluster Cardiopulmonary System, and of the Universities of Giessen and Marburg Lung Center, which is part of the German Center of Lung Research. In addition, he is Director of Pneumology at the Kerckhoff Heart and Lung Center in Bad NAuheim, Germany. Professor Ghofrani has participated in the therapeutic development of surfactants, prostanoids, PDE-5 inhibitors, combination therapies, soluble guanylate cyclase (sGC) activators/stimulators, endothelin receptor antagonists, and tyrosine kinase inhibitors. He has received numerous awards and is a reviewer for several journals, including the American Journal of Respiratory and Critical Care Medicine, European Respiratory Journal, Circulation, and Lancet.

ABOUT THE ACTELION / NIPPON SHINYAKU ALLIANCE
In April 2008, Actelion and Nippon Shinyaku entered into an exclusive worldwide alliance, under which Actelion is responsible for global development and commercialization of selexipag outside Japan, while the two companies will co-develop and co-commercialize in Japan. Nippon Shinyaku will receive milestone payments based on development stage and sales milestones as well as royalties on any sales of selexipag.