European Respiratory Journal Publishes Phase II Study of Investigational Oral Agent Riociguat in Treatment of Pulmonary Hypertension

WAYNE, N.J., June 11 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals, Inc. today announced that the study "Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study" was published online this week by the European Respiratory Journal.*  Results of this study to assess the safety, tolerability and the feasibility of individual dose titration of riociguat were previously presented at the 2009 International Conference of the American Thoracic Society.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two debilitating forms of pulmonary hypertension (PH) with low survival rates.  Riociguat (BAY 63-2521) is an investigational oral agent being studied for the potential treatment of PH that targets soluble guanylate cyclase (sGC), a receptor for nitric oxide (NO).  

According to the published results, 96 percent of the patients enrolled completed the study, and the majority of patients (72 percent) were able to be titrated from the starting dose of 1 mg t.i.d. by 0.5 mg increments every two weeks to a maximum target dose of 2.5 mg t.i.d.  Sixty-five patients (87 percent) who received at least one dose of riociguat reported an adverse event (AE), including 11 serious adverse events (SAE).  Adverse events were judged to be drug-related in 42 patients (56 percent), and most (96 percent) were considered mild or moderate in severity.  The incidence of AEs was not considered related to the dose of riociguat.  Dyspepsia, headache and hypotension were the most-frequently reported adverse events (AEs), and three participants (4 percent) discontinued the study because of AEs (two due to SAEs; one with pulmonary edema related to pulmonary venous occlusive disease and one with progressive right heart failure).  The publication also describes the effects of riociguat on secondary pharmacodynamic endpoints.

"Pulmonary hypertension is a severe and life-threatening disease that progresses rapidly and, despite advances in patient care over the last few years, there is a real need for additional therapies," said lead investigator Prof. Hossein Ardeschir Ghofrani, Head of the Pulmonary Hypertension Division, Department of Internal Medicine, University of Giessen, Germany. "These preliminary findings support further research and randomized clinical trials to determine the efficacy and safety of riociguat as a potential treatment for these forms of pulmonary hypertension are underway."

About the Phase II Study Results

Seventy-five patients (42 patients with CTEPH and 33 patients with PAH) participated in the 12-week, multicenter, open-label, uncontrolled phase II trial.  The primary endpoints of the Phase II study assessed safety, tolerability and the feasibility of individual dose titration of riociguat.  Secondary endpoints measured in the study included change from baseline in six-minute walking distance (6-MWD), modified Borg dyspnea score and change in functional class according to the World Health Organization (WHO) classification.  Changes from baseline in cardiopulmonary hemodynamics were also assessed in patients who agreed to undergo a second right heart catheterization procedure.  

The 12-week study was completed by 72 of the 75 patients (96 percent; 41 CTEPH and 31 PAH).  At the end of the study, 52 patients (72 percent) were receiving at least the maximum dose of riociguat (greater than or equal to 2.5 mg t.i.d.) and four patients (5 percent) were at the starting dose (1 mg t.i.d).  One patient (1 percent) ended the study on 0.5 mg t.i.d.  The riociguat dose was reduced by 0.5 mg because of asymptomatic hypotension in two patients.  

Three patients (4 percent) discontinued the study because of adverse events.  Adverse events (AEs) were reported by 65 study participants (87 percent), 11 of whom experienced serious adverse events (SAEs).  Forty-two patients (56 percent) were considered to have experienced drug-related AEs.  Ninety-six percent of the drug-related AEs were judged to be mild or moderate in severity and were not considered related to the dose of riociguat.  Dyspepsia, headache and hypotension were the most-frequent AEs.  Asymptomatic hypotension (systemic blood pressure (SBP) <90mmHg) occurred in 11 patients, but blood pressure normalized without dose alteration in nine patients and after dose reduction in two patients.  Syncope was reported in four patients but was not considered to be drug-related because independent causes could be identified, and did not require lowering the dose of riociguat.

Compared to baseline, riociguat significantly increased median 6-MWD.  By the end of the study, the median 6-MWD had increased in 86 percent of participants (by >50 m in 54 percent and by >100 m in 29 percent) and significant increases in median 6-MWD were observed in the whole study population of 55 m (20.0 – 107.0 m; p<0.0001), as well as in the CTEPH subgroup of 55m (17.0 – 105.0 m; p<0.0001) and PAH subgroup of 57m (25.0 – 117.0; p<0.0001).   During the 12-week study, the median modified Borg dyspnea score improved by one point on a 10-point scale compared to baseline.  In total, 22 of 72 patients (31 percent) showed an improvement in WHO functional class, and one patient deteriorated.  In the 50 patient who underwent a second right heart catheterization procedure, significant hemodynamic improvements were also seen compared to baseline in the whole study population, as well as in the CTEPH and PAH subgroups.

About Riociguat (BAY 63-2521)

Identified and developed at the Bayer research laboratories, riociguat is a developmental oral agent being investigated in ongoing, randomized, placebo-controlled Phase III clinical trials as a potential treatment option for chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH), two life-threatening types of PH.  A soluble guanylate cyclase (sGC) stimulator, riociguat has been shown in pre-clinical studies to directly stimulate sGC and to enhance the action of nitric oxide (NO), an important messenger molecule that is involved in many physiological and pathological processes in the body.  A pathway involving NO is an area of investigational interest because the amount and effects of nitric oxide are thought to be impaired in patients with forms of pulmonary hypertension.  

More information about riociguat clinical trials can be found at www.clinicaltrials.gov.

About Bayer HealthCare Pharmaceuticals Inc.

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, General Medicine, which includes Cardiology and Primary Care and Specialty Medicine, which includes Hematology, Oncology and Multiple Sclerosis. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

*Ghofrani HA, Hoeper MM, Halank M, et al. Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Published online before print June 7, 2010 Eur Respir J 2010, doi: 10.1183/0931936.00182909

SOURCE Bayer HealthCare Pharmaceuticals, Inc.