Bayer HealthCare has filed riociguat for the treatment of pulmonary arterial hypertension (PAH) for regulatory approval in Japan. PAH is a progressive and life-threatening form of pulmonary hypertension in which the blood pressure in the pulmonary arteries is significantly increased due to vasoconstriction and which can lead to heart failure and death. In January 2014, the MHLW in Japan had approved riociguat under the trade name Adempas in another life-threatening form of pulmonary hypertension, namely chronic thromboembolic pulmonary hypertension (CTEPH).
“In the pivotal Phase 3 clinical trial, PAH patients who received riociguat observed rapid and significant improvements with regard to the severity of their disease and to their symptoms,” said Dr. Jörg Möller, member of the Bayer HealthCare Executive Committee and head of global development. “Moreover, these improvements were sustained over the long-term. Effective therapeutic options are needed in the treatment of a progressive disease where mortality remains high in spite of several drugs already available, so we hope to be able to bring riociguat to PAH patients and their treating physicians in Japan soon.”
Riociguat is the first oral treatment to show early, significant and sustained clinical efficacy in Phase 3 clinical trials across multiple clinically relevant endpoints in patients with PAH, either as a monotherapy or in combination with certain other medicines used to treat PAH, such as endothelin receptor antagonists (ERAs) or non-intravenous prostacyclin analogue (PCA) therapies. So far no other oral drugs, including PDE5-inhibitors, have been able to show this. Riociguat significantly improved the patient’s ability to walk farther, helping the heart and lungs work better and making breathing easier when performing everyday basic tasks. Consequently, PAH patients who received riociguat observed reductions in disease severity and these improvements are sustained over long-term.
The submission of riociguat in PAH in Japan is based on results from the randomized, double-blind, placebo-controlled, global Phase 3 study PATENT-1 as well as long-term data from PATENT-2 available at the time. These assessed the efficacy and safety of oral riociguat in the treatment of PAH. The PATENT-1 study met its primary endpoint by demonstrating a statistically significant improvement (p<0.0001) from baseline in the six-minute walk test (6MWT), a marker of disease severity and predictor of survival, after 12 weeks compared with placebo. Additionally, statistically significant improvements were observed across a broad range of clinically relevant secondary endpoints, including WHO functional class (FC), time to clinical worsening (TTCW), Borg dyspnea score, hemodynamic parameters (cardiac output, pulmonary vascular resistance (PVR), mPAP) and a disease-related biomarker, N-terminal prohormone brain natriuretic peptide (NT-pro BNP), PATENT-1 included both treatment naïve symptomatic PAH patients and those pre-treated with ERAs or non-iv prostanoid. Results of the PATENT-1 study were published in the New England Journal of Medicine (NEJM) in July 2013.
Date: April 23, 2014