Bayer receives approval for Adempas® as first drug to treat rare heart and lung disease

• Adempas® (riociguat) offers new hope for patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH)
• Adempas^® is now available in Canada as the first and only drug indicated to manage the treatment of chronic thromboembolic pulmonary hypertension (CTEPH)^1,2

TORONTO, Sept. 23, 2013 /CNW/ - Bayer Inc. announced today the Health Canada approval of Adempas® (riociguat). Adempas® is the first drug indicated to manage the treatment of inoperable, or persistent /recurrent chronic thromboembolic pulmonary hypertension (CTEPH) after surgery in adult patients with World Health Organization Functional Class II or III pulmonary hypertension.^1,2

CTEPH is an uncommon form of pulmonary hypertension (PH), a severe, progressive and life-threatening condition of the heart and lungs that affects up to several thousand people in Canada.³ Patients with PH develop high blood pressure in the arteries of the lungs, which causes breathlessness and fatigue, hindering their ability to work and carry out everyday activities, like walking - even a short distance - in some cases.^4,5,6,7,8

"Before today, we had no proven drug treatments for patients with inoperable CTEPH or patients in whom surgery was not successful in curing their CTEPH. Adempas gives us an effective drug treatment with proven clinical efficacy and good tolerability," said Dr. John Granton, Head, Division of Respirology University Health Network, Mount Sinai Hospital, and Women's College Hospital. He added that, because of the complex nature of PH, "Patients should be referred to an expert PH centre as soon as possible for a thorough assessment and timely treatment."

Results from a major clinical trial showed that riociguat is the first ever drug to provide statistically significant clinical improvement in patients with inoperable CTEPH or persistent/recurrent PH disease at the end of 16 weeks of treatment. Improvements were seen in a range of disease-related measures such as reduction in patients' resistance to blood flow in the arteries of the lungs, and in markers of disease severity.⁹ Riociguat also significantly improved their exercise capacity measured by a six-minute walk test (6MWT).⁹

"Riociguat will be welcomed by patients with CTEPH who, up to now, have not had a proven drug treatment option available to them if their disease is inoperable or for those experiencing residual PH following surgery. CTEPH is a devastating diagnosis, and the symptoms of breathlessness, dizziness and fainting can be frightening and have a severe impact on daily activities. To have a treatment that achieves meaningful clinical improvements is a much needed step forward," said Frank Poon, President, Pulmonary Hypertension Association of Canada.

The standard and potentially curative treatment option for patients who have developed CTEPH is a surgical procedure called pulmonary endarterectomy that mechanically clears the blood vessels of the lungs of scar tissue caused by the disease.¹⁰ However, the disease persists or recurs after surgery in up to 35% of patients.¹¹ Many patients (20%-50%)^12,13 with CTEPH are not candidates for surgery and, like patients with residual PH, urgently need effective new treatments to manage their disease.¹⁴

Long-term trials of the riociguat study program in CTEPH are ongoing, and first results show that safety and tolerability as well as efficacy (change in 6MWT) are sustained over one year.¹⁵

About Pulmonary Hypertension
PH is a severe, progressive, life-changing and life-threatening disorder of the heart and lungs in which blood pressure in the pulmonary arteries is above normal, and which can lead to heart failure and death.^4,5 Patients with PH develop a markedly decreased exercise capacity and a reduced quality of life.⁸ The most common symptoms of PH include shortness of breath, fatigue, dizziness and fainting, all of which are worsened by exertion.^6,7 As the symptoms of PH are non-specific, diagnosis can be delayed by as much as two years.^8,16,17 Early diagnosis is essential and accurate identification of the PH type is essential as a delay in treatment initiation can have a negative impact on survival.^8,18 Continuous treatment monitoring is then vital to ensure that patients are receiving optimal care for their particular type and stage of disease.⁸

There are five different types of PH and each can affect the patient in a different way and every patient may have a different etiology and manifestation of PH.^8,10,16 For the best chance of success patients need to be treated at an expert PH centre. ^8,19

About Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
CTEPH is a progressive and life-threatening disease and a type of PH in which it is believed that thromboembolic occlusion (organized blood clots) of pulmonary vessels gradually lead to increased blood pressure in the pulmonary arteries, resulting in an overload of the right heart.^8,10 CTEPH may evolve after prior episodes of acute pulmonary embolism, but the pathogenesis is not yet completely understood.¹⁰ The standard and potentially curative treatment for CTEPH is pulmonary endarterectomy (PEA), a surgical procedure in which the blood vessels of the lungs are cleared of clot and scar tissue.¹⁰ However, a considerable number of patients with CTEPH (20%-50%) are inoperable and in up to 35% of patients, the disease persists or recurs after PEA. These patients need an effective pharmacological treatment.¹⁴

About Riociguat
Riociguat is a soluble guanylate cyclase (sGC) stimulator, the first member of a novel class of compounds developed by Bayer to target a key molecular mechanism underlying PH. sGC is an enzyme found in the cardiopulmonary system and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme enhances synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP). cGMP plays an important role in regulating vascular tone, proliferation, fibrosis, and inflammation.

PH is associated with endothelial dysfunction, impaired synthesis of NO and insufficient stimulation of sGC. Riociguat has a unique mode of action - it sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO. Riociguat, as a stimulator of sGC, addresses the issue of NO deficiency by restoring the NO-sGC-cGMP pathway, leading to increased generation of cGMP.

With its novel mode of action, riociguat has the potential to overcome a number of limitations of currently approved PAH therapies, including NO dependence. It is the first drug which has shown clinical benefits in CTEPH, where, until the approval of riociguat, no indicated pharmacological treatment was available.^1,2

About Bayer in Canada
Bayer Inc. is a Canadian subsidiary of Bayer AG and the headquarters for its Canadian operations.  Celebrating its 150^th anniversary, Bayer AG is an international research-based group with core businesses in healthcare, crop science and innovative materials committed to creating a better life for all through science.  In Canada, Bayer operates its healthcare business - Pharmaceuticals, Consumer Care, Diabetes Care, Animal Health and Radiology & Interventional - from its headquarters in Toronto, ON and its CropScience business from Calgary, AB. With more than 1,300 employees across the country, in 2012, Bayer had sales of $1.6 billion and invested $55.9 million in research and development in Canada. Globally, Bayer AG had sales of €39.8 billion and invested €3 billion in research and development.

For more information about Bayer Inc., please visit www.bayer.ca.

Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup 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 Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

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¹ Mayer, E. Surgical and post-operative treatment of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2010;19:64-67
² ADEMPAS Product Monograph, September 17, 2013
³ Marc de Perrot, MD, Karen McRae, MD, Yaron Shargall, MD, Laura Pletsch, RN, Kongteng Tan, MD, Peter Slinger, MD, Martin Ma, MD, Narinder Paul, MD, Jakov Moric, MD, John Thenganatt, MD, Susanna Mak, MD, and John T. Granton, MD. Clinical Research Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension: The Toronto Experience. Canadian Journal of Cardiology 27 (2011) 692-697
⁴ Rosenkranz, S. Pulmonary hypertension: current diagnosis and treatment. Clin Res Cardiol 2007;96:527-541
⁵ Macchia, A et al. A meta-analysis of trials of pulmonary hypertension: A clinical condition looking for drugs and research methodology. Am Heart J 2007;153:1037-1047
⁶ McKenna, S et al. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): A measure of health-related quality of life and quality of life for patients with pulmonary hypertension. Qual Life Res 2006;15:103-115
⁷ PHA UK website. Available from: http://www.phassociation.uk.com/what_is_ph/ Last accessed: May 2013
⁸ Galiè, N et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009;30:2493-2537
⁹ Ghofrani, HA et al. Riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension: a randomized, double-blind, placebo-controlled study (CHEST-1). ACCP 2012, Atlanta, USA. Oral abstract 1462924
¹⁰ Ali, JM et al Chronic thromboembolic pulmonary hypertension: An underdiagnosed entity? Hosp Pract 2012;40:71-9
¹¹ Rahnavardi M, Yan TD, Cao C, Vallely MP, Bannon PG, Wilson MK. Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension: a systematic review. Ann Thorac Cardiovasc Surg. 2011;17(5):435-445.
¹² Mayer E, Jenkins D, Lindner J, et al. Surgical management and outcome of patients with chronic thromboembolic hypertension: results from an international prospective registry. J Cardiovasc. Surg. 2011. 702-710.
¹³ Humbert, M. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology. Eur Respir Rev 2010;19:59-63
¹⁴ Humbert, M. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology. Eur Respir Rev 2010;19:59-63
¹⁵ Simonneau, G et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH): A Phase III long-term extension study (CHEST-2). 5th World Symposium of Pulmonary Hypertension (WSPH) 2013, Nice, France. Poster Presentation.
¹⁶ Armstrong, I et al. The trajectory to diagnosis with pulmonary arterial hypertension: a qualitative study. BMJ Open 2012; 2:e000806
¹⁷ Peacock, JA. Treatment of pulmonary hypertension. BMJ 2003; 326:835-836
¹⁸ Vachiery, J-L et al. How to detect disease progression in pulmonary arterial hypertension. Eur Respir Rev 2012; 21:40-47
¹⁹ Ghofrani, HA et al. Treatment of pulmonary arterial hypertension (PAH): updated recommendations of the Cologne Consensus Conference 2011. Int J Cardiol 2011;154(Suppl 1):S20-S33

SOURCE: Bayer Inc.

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Laura Burns
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