Clinical Trials

Riociguat (BAY 63-2521) is an oral agent being investigated as a new approach to treating different types of pulmonary hypertension. Riociguat is the first member of a novel class of compounds, the stimulators of enzyme found in the cardiopulmonary system, soluble guanylate cyclase (sGC). When nitric oxide (NO) binds to sGC, the enzyme catalyzes synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP), which plays an important role in regulating vascular tone, proliferation, fibrosis, and inflammation. The ability of riociguat to directly stimulate sGC independent of NO while also increasing the sensitivity of sGC to NO is potentially important in PAH. Endothelial dysfunction associated with PAH can be related to low levels of NO.

PATENT-2 is the open-label long-term extension trial of the multi-center, multi-national PATENT Phase III study program currently being conducted in 30 countries.(1) In the randomized, double-blinded, placebo controlled pivotal PATENT-1 trial, treatment-naïve or pre-treated PAH patients received over 12 weeks either placebo or riociguat in two different dose titration arms, an individual and an exploratory capped dose titration arm. Approximately 90% of patients from PATENT-1 entered the PATENT-2 trial, which aims to investigate the longer term safety profile of riociguat in PAH patients as primary outcome. In addition, the sustainability of the efficacy results of PATENT-1 including 6MWD and WHO FC were measured as secondary outcomes

* On May 20, 2013 - Bayer HealthCare has announced positive data from the interim analysis of the on-going PATENT-2 trial with riociguat, the open-label long-term extension of the pivotal Phase III study PATENT-1, at the American Thoracic Society International Conference, Philadelphia, USA. The results support the positive data of the pivotal PATENT-1 trial, showing long-term safety and sustained clinical benefits in patients with pulmonary arterial hypertension (PAH).

In the first interim analysis of PATENT-2, riociguat was shown to be well tolerated with a good long-term safety profile in both treatment-naïve and pre-treated PAH patients.  Adverse events were reported in 334 (92%) of patients during PATENT-2, of which 185 (51%) patients developed drug-related adverse events. The most frequent drug-related adverse events (>5%) were headache (8%), dizziness (8%), dyspepsia (7%), hypotension (5%). Serious adverse events were reported by 140 (39%) patients, of which 17 (5%) were considered drug-related by the investigator.
Further improvements in six minute walking distance (6MWD) were seen with continued riociguat treatment. After an additional 12 weeks of treatment in PATENT-2, the 6MWD had increased further in former riociguat patients compared with baseline of the pivotal PATENT-1 trial.  After 12 weeks in PATENT-2, the 6MWD had increased by 53 meters (former individual titration arm of riociguat), 54 meters (former capped dose titration arm of riociguat) and 42 meters (former placebo arm) against PATENT-1 baseline.In the cohort of patients that have reached one year of study treatment, the increase in 6MWD was 48 meters compared with PATENT-1 baseline. However, this promising result must be interpreted with caution until the complete 1-year data set for the overall population in PATENT-2 is available.

After 12 weeks in PATENT-2, improvement in WHO FC was recorded in 34%, 33% and 22% of the former individual titration arm of ricoguat, the former capped-dose titration arm of riociguat and the former placebo arm respectively.(1) In the cohort of patients that have reached one year of study treatment, WHO FC had improved in 36%, stabilized in 58% and worsened in 7% of patients compared with PATENT-1 baseline.(1, 2) Again, this promising result must be interpreted with caution until the complete 1-year data set for the overall patient population is available.

At one year, 96% of patients in PATENT-2 were still alive and 86% were free from clinical worsening. Overall, 46 (13%) patients received an additional PH medication during PATENT-2.

The presentation of these positive data follows the recent priority review granted to riociguat by the FDA  for its U.S. approval.