Based on positive Phase II trial findings, Bayer Schering Pharma will move into Phase III trials with its oral agent riociguat (BAY 63-2521). Riociguat is the first member of a new class of vasodilating agents called soluble guanylate cyclase (sGC) stimulators. It is being investigated as a new approach for the treatment of different forms of pulmonary hypertension. Riociguat demonstrated significantly improved exercise capacity in a Phase II study in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) as compared to baseline values. The Phase III program for these indications is planned to be initiated in late 2008.
Top-line findings from the open-label, uncontrolled Phase II study were presented today during a Bayer Schering Pharma satellite symposium at the Annual Congress of the European Respiratory Society (ERS) in Berlin, Germany. In addition to significantly increased exercise capacity, patients improved as well in terms of hemodynamic parameters such as pulmonary vascular resistance, cardiac output and pulmonary arterial pressure in comparison to baseline values. The study also showed that riociguat was well tolerated and had a favorable safety profile. Further data from the study are planned to be presented at the American Thoracic Society (ATS) International Conference in May 2009, in San Diego, California, USA.
"Riociguat has the potential to overcome limitations of current standards of care in pulmonary hypertension," said Kemal Malik, M.D., Head of Global Development and Member of the Executive Committee of Bayer HealthCare. "We are expanding into areas of high unmet medical need and riociguat is an example of the kind of novel approach to treating cardiovascular disease to which Bayer is committed."
"Pulmonary hypertension is a life threatening disease and the majority of patients are still left without a viable treatment option," said lead investigator Prof. Hossein Ardeschir Ghofrani, Head of the Pulmonary Hypertension Division, Department of Internal Medicine, University of Giessen, Germany. "We are very encouraged by the beneficial effects of riociguat in our study. If these findings are replicated in the upcoming Phase III trials, it will be good news indeed for patients with pulmonary hypertension and the physicians who treat them."
In addition to the completed Phase II study and the two Phase III trials in CTEPH and PAH about to begin, further Phase II studies of riociguat are underway in patients suffering from other forms of pulmonary hypertension (PH) such as PH in patients with interstitial lung disease (PH-ILD) or PH in patients with chronic obstructive pulmonary disease (PH-COPD). First results from these studies are currently expected for 2011 and 2009, respectively.
About the Phase II study in PAH/CTEPH
This Phase II trial was a 12-week, open-label, uncontrolled study conducted in 75 patients suffering from CTEPH and PAH. The exercise capacity was measured by the "six-minute distance walked", a standard test that has been used as a primary endpoint in previous pivotal clinical studies in patients
with pulmonary hypertension. Riociguat significantly improved the exercise capacity in a clinically meaningful manner for all patients as well as for the subgroups with PAH and CTEPH, accordingly. In addition to this finding, CTEPH and PAH patients significantly improved in their pulmonary hemodynamics measures as well as in their heart failure stage according to a standard functional classification system established by the New York Heart Association (NYHA). The study also showed riociguat was well tolerated and had a favorable safety profile.
About Pulmonary Hypertension
Pulmonary hypertension (PH) affects more than 2.5 million people worldwide, but the majority of patients are without approved treatment. The disease involves an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, leading to shortness of breath, dizziness,
fainting, and other symptoms, all of which are worsened by exertion. PH can be a severe disease with a markedly decreased exercise tolerance, and can lead to heart failure and death.
There are five main categories of PH according to WHO (World Health Organization): chronic thromboembolic pulmonary hypertension (CTEPH); pulmonary arterial hypertension (PAH); PH with left ventricular disease (PH-LVD); and PH with lung disease and/or hypoxemia, which include PH with chronic obstructive pulmonary disease (PH-COPD) and PH with interstitial lung disease (PH-ILD); as well as a category containing miscellaneous indications not included in the aforementioned groups. The different categories of PH have different underlying causes, and therefore may need to be treated differently. Unfortunately, the only approved therapies currently available are for PAH, which comprises only a small proportion of PH cases. Even with current therapy, the median survival time for a patient with PAH is only 5 to 6 years following diagnosis, underscoring the need for new treatments.
About Riociguat
Riociguat is a member of a novel class of therapeutics called soluble guanylate cyclase (sGC) stimulators, and is being investigated as a new approach for the treatment of CTEPH and PAH, as well as other forms of PH.
Riociguat works through the same signaling pathway as the body's own vasodilating substance, nitric oxide (NO). NO relaxes blood vessels and relieves the lung and heart by modulating the activity of the enzyme soluble guanylate cyclase (sGC).
Riociguat is capable of directly stimulating sGC, bringing the enzyme into a status that makes it more sensitive to the effects of endogenous NO. Riociguat is effective in treating PAH, and decreasing the associated right heart hypertrophy and vascular remodeling in animal models.
Because riociguat acts directly on sGC, it avoids the shortcomings of NO-based therapies. Additionally, riociguat has the potential to overcome a number of limitations of other therapies currently used for PH, including phosphodiesterase-5 (PDE-5) inhibitors, endothelin receptor antagonists, and prostacyclin analogues.
About Bayer Schering Pharma
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary of Bayer AG, is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals divisions. The pharmaceuticals business operates under the name Bayer Schering Pharma AG.
Bayer HealthCare's aim is to discover and manufacture products that will improve human and animal health worldwide. Find more information at www.bayerhealthcare.com.
Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company. Its research and business activities are focused on the following areas: Diagnostic Imaging, General Medicine, Specialty Medicine and Women's Healthcare. With innovative products, Bayer Schering Pharma aims for leading positions in specialized markets worldwide. Using new ideas, Bayer Schering Pharma aims to make a contribution to medical progress and strives to improve the quality of life. Find more information at www.bayerscheringpharma.de.