IR News 2016

 Nippon Shinyaku Co., Ltd. (HQ: Kyoto, President: Shigenobu Maekawa) today announced that it was granted a manufacturing and marketing authorization for Uptravi^® (generic name: selexipag, development code: NS-304) by the Ministry of Health, Labor and Welfare (MHLW) for the treatment of pulmonary arterial hypertension (PAH). Uptravi was originally discovered and synthesized by Nippon Shinyaku Co., Ltd. and was jointly developed in Japan with Actelion Pharmaceuticals Japan Ltd. (HQ: Tokyo, President: Satoshi Tanaka).

 PAH is a disease with a poor-prognosis, characterized by an abnormally increased blood pressure in the pulmonary artery from any cause and is classified as either idiopathic PAH (PAH of unknown cause) or associated PAH (PAH secondary to certain diseases such as connective tissue disease and congenital heart disease). Treatment for PAH includes prostacyclin receptor (IP receptor) agonists, endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitors (PDE5i).

 Uptravi is the first-in-class, orally active, selective IP prostacyclin receptor agonist which is approved and launched as a treatment for PAH in number of countries including the United States and Europe. Uptravi shows long-term efficacy in PAH by inducing vasodilation and inhibiting proliferation of vascular smooth muscle cells.

 Uptravi was approved by the health authorities in USA and Europe, based on the excellent clinical data of the multinational phase 3 study (GRIPHON study^*), conducted by Actelion Pharmaceuticals Ltd. which is our global partner. It was launched in USA in this January and Germany in Europe in this June as well as in Canada in this June by Actelion Pharmaceuticals Ltd. Uptravi was also approved in Australia, New Zealand, South Korea and Switzerland.

　In addition to marketing Opsumit (ERA) and Adcirca (PDE5i), Nippon Shinyaku hopes to contribute further to the improvement of PAH treatment in Japan by making the novel IP prostacyclin receptor agonist, Uptravi, available to the patients as soon as possible.

　In Japan, Nippon Shinyaku will co-promote Uptravi and Opsumit in collaboration with Actelion Pharmaceuticals Japan Ltd.

* GRIPHON study

The GRIPHON study was a long-term and an event-driven clinical trial, designed to demonstrate a prolongation in time to the first morbidity and mortality event for Uptravi compared to placebo, enrolling 1,156 patients from 39 countries. The exposure to Uptravi was up to 4.2 years. The risk of a primary composite endpoint event of morbidity and mortality was reduced by 40% (p<0.001) with Uptravi compared to placebo. The benefit of Uptravi was consistent across pre-specified patient subgroups such as age, gender, PAH classification, WHO functional class, and use of medication for PAH, including patients receiving an ERA and a PDE-5 inhibitor at baseline (n = 376; 32.5%).