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First Phase II study in patients with pulmonary hypertension owing to interstitial lung disease meets primary objectives / First long-term extension data of Phase II study in chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension show sustained improvement in exercise capacity
New Orleans, LA, USA & Berlin, Germany | May 18, 2010 | Bayer Schering Pharma presented today positive data from a Phase II trial with its oral agent riociguat (BAY 63-2521) in patients with pulmonary hypertension owing to interstitial lung disease (PH-ILD) at the American Thoracic Society (ATS) international conference in New Orleans, USA. PH-ILD is a severe and life threatening form of pulmonary hypertension. The study found riociguat reduced pulmonary vascular resistance (PVR), increased cardiac output and improved exercise capacity slightly as measured by the six-minute walk test (6-MWT) in patients with PH-ILD.(1) Riociguat was also found to be well tolerated and had a favorable safety profile in the study.
“PH-ILD is a form of pulmonary hypertension for which no approved treatment options are currently available,” said Professor Marius Hoeper, Hannover Medical School, Germany, lead investigator of the trial. “These Phase II results show encouraging signals for further investigation of riociguat in PH-ILD. We hope physicians may be provided with a treatment option for this deadly disease in the future.“
Riociguat is the first member of a novel class of therapeutics called soluble guanylate cyclase (sGC) stimulators and is being investigated as a new approach to treat different forms of pulmonary hypertension.
Also presented at the ATS 2010 congress were the first long-term extension data from a Phase II study of riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Data from the 12-week, multicentre, open-label, uncontrolled, phase II trial was presented at the ATS 2009 congress. 68 of 75 patients who completed this Phase II study entered the long-term extension (LTE) phase (CTEPH, 41 & PAH, 27).(2) The improvements in 6-MWT seen following riociguat-treatment in the 12-week trial were sustained for at least 15 months of the LTE in PAH and also in CTEPH patients. Riociguat was generally well tolerated with a favorable safety profile. The LTE phase started in mid 2007 and is planned to end late 2011. Currently, a large Phase III trial program in patients with CTEPH and PAH is ongoing.
“These first LTE results for riociguat are very promising. However, they are just a small part of the extensive clinical development program exploring the potential of riociguat for patients suffering from pulmonary hypertension, including forms for which there are currently no drug therapies available,” said Dr. Frank Misselwitz, Vice President of Global Clinical Development and Head of the Cardiovascular and Coagulation Therapeutic Area, Bayer Schering Pharma AG.
Riociguat is currently in parallel clinically investigated in several non-PAH forms (PH-ILD, PH-LVD, PH-COPD, and CTEPH). After a successful proof of concept study in pulmonary hypertension owing to left ventricular systolic dysfunction (PH-LVD) a Phase IIb study (LEPHT) was initiated and first patient enrolled in April 2010. Proof-of-concept was also demonstrated in a single dose study with riociguat in patients with pulmonary hypertension owing to chronic obstructive pulmonary disease (PH-COPD). The data of this study is planned to be release during the course of this year. Bayer Schering Pharma is committed to proceed to the next steps in the clinical development of riociguat in PH-ILD and PH-COPD.
About PH-ILD Phase II Study
A multicenter, open-label, uncontrolled Phase II study was conducted in patients with pulmonary hypertension owing to interstitial lung disease (PH-ILD). 21 patients received individual doses of up to 2.5 mg riociguat three times daily for 12 weeks. The objective of the study was to investigate the safety and tolerability of riociguat. In addition, pulmonary hemodynamics, blood gases and exercise capacity measured by the six-minute walk test (6-MWT) as well as other parameters were assessed after 12 weeks of drug treatment and compared to baseline values. The pulmonary vascular resistance (PVR) decreased from 659 ± 205 dyn.s/cm5 at baseline to 537 ± 186 dyn.s/cm5 and cardiac output increased from 4.3 ± 1.4 L/min at baseline to 5.6 ± 1.8 L/min. The six-minute walk test (6-MWT) results improved slightly from 321 ± 95 m at baseline to 342 ± 113 m at 12 weeks.(1)
About PH-ILD
Pulmonary hypertension owing to interstitial lung disease (PH-ILD) is a severe and life-threatening disorder in which the pressure in the pulmonary arteries is above normal. In PH-ILD patients, underlying interstitial lung disease is the cause of the development of PH. ILD summarizes a heterogenous group of lung diseases with similar clinical radiographic, and physiologic manifestations (e.g. pulmonary fibrosis). ILD then causes PH to develop through a phenomenon referred to as “vascular remodelling”, which causes a restricted flow through the pulmonary circulation resulting in increase in pulmonary vascular resistance and ultimately in right heart failure and death.(3) Within PH, PH-ILD has a global prevalence of approximately 64,000 patients.(4)
About Pulmonary Hypertension
Pulmonary Hypertension (PH) is a disorder in which the pressure in the pulmonary arteries is above normal. People with PH develop a markedly decreased exercise tolerance and reduced quality of life. Early PH is often asymptomatic. By the time symptoms appear, disease progression is usually well advanced. The most common symptoms of PH include shortness of breath with physical exercise (exertional dyspnea), fatigue, dizziness and fainting, all of which are worsened by exertion. PH is a severe and life-threatening disease that can lead to heart failure and death. According to the WHO classification, there are five different types of PH based on the underlying causes of pulmonary hypertension.
About Riociguat
Riociguat (BAY 63-2521), identified and developed at the Bayer research laboratories, is an oral agent being investigated in Phase III clinical trials as a potential new approach to treating chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH), two life-threatening types of PH. Riociguat is the first member of a novel class of therapeutics called soluble guanylate cyclase (sGC) stimulators. Riociguat works through the same signalling pathway as the body’s own vasodilating substance, nitric oxide (NO). NO relaxes the musculature in the blood-vessel walls, lowers the pulmonary blood pressure and relieves the heart by modulating the activity of the sGC enzyme. Riociguat has a dual mode of action: it sensitizes sGC to the body’s own NO while also directly stimulating sGC independently of NO. This could be important because the NO levels in the pulmonary circulation are decreased in patients with PH. With its novel mode of action, riociguat has the potential to overcome a number of limitations of currently approved PAH therapies and may be effective in forms of PH where no treatment is approved, like CTEPH and PH-ILD. Riociguat is also an ideal fit to the already existing cardiovascular and respiratory competencies of Bayer Schering Pharma, Germany, being also already at the forefront of PAH treatment with Ventavis® (inhaled iloprost).
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of healthcare, 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, Bayer Schering Pharma, Consumer Care and Medical Care divisions. Bayer HealthCare’s aim is to discover, manufacture and market products that will improve human and animal health worldwide. Find more information at www.bayerhealthcare.com.
About Bayer Schering PharmaBayer 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.
References:
(1.) Hoeper et al.: Riociguat for patients with pulmonary hypertension associated with interstitial lung disease. Poster presented at the American Thoracic Society congress May 18th, 2010.
(2.) Ghofrani et al. : Riociguat for Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension: First Long-term Extension Data from a Phase II Study. Abstract presented at the American Thoracic Society congress May 17th, 2010.
(3.) Rosenkranz S.: Pulmonary hypertension: current diagnosis and treatment. Clin Res Cardiol 2007;96(8):527-41.
(4.) Estimate by Bayer Schering Pharma based on citation from Peacock AJ.: Treatment of pulmonary hypertension. BMJ 2003; 326: 835-6, that severe pulmonary hypertension has a total prevalence of about 30-50/million.
SOURCE: Bayer Schering PharmaBayer Schering |
