Adempas® now approved for second rare heart and lung disease, offering a new treatment option to improve patient care

• Bayer's Adempas (riociguat tablets) approved for the treatment of pulmonary arterial hypertension (PAH)¹, which affects up to 2000 Canadians²
• Adempas provides novel and specific approach to treat different types of pulmonary hypertension (PH), a serious condition of the heart and lungs
• Only drug in Canada indicated to treat two rare types of PH – PAH and chronic thromboembolic pulmonary hypertension (CTEPH)^1,3

TORONTO, March 10, 2014 /CNW/ - Bayer Inc. announced today the approval of Adempas® (riociguat tablets) for treating patients with a form of heart and lung disease called pulmonary arterial hypertension (PAH).¹ Adempas is currently the only treatment approved for use in two rare types of pulmonary hypertension (PH) – PAH and chronic thromboembolic pulmonary hypertension (CTEPH).^1,4,5

PAH is a rare form of PH, a severe, progressive and life-threatening heart and lung condition affecting up to 2000 Canadians.² 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.^6,7,8,9,10

"It is important to have effective options to treat complex and rare diseases like pulmonary hypertension. Adempas provides us with a novel treatment option for patients that has a proven efficacy and safety profile," said Dr. David Langleben, Cardiology Division, Jewish General Hospital and Director, Centre for Pulmonary Vascular Disease. He added, "Adempas also introduces a new class of drugs to the market, providing progress in the treatment of a disease that continues to see high mortality rates."

Prognosis for patients suffering from PAH is poor despite the availability of three other classes of approved PAH therapies.^11,12 Mortality rates remain high at 15% within one year of diagnosis, while one third (32%) of patients die within three years of diagnosis.¹¹

In a pivotal trial (PATENT), Adempas demonstrated statistically significant efficacy in the treatment of PAH, taken alone or in combination with other PAH therapies. Adempas showed improvements in exercise capacity, in a range of disease related symptoms, in the speed of disease progression and in markers of disease severity.⁵    

"We are pleased that patients will have another option to manage this devastating and rare disease. As new therapies come to market, it is paramount that we also ensure patients have access to these life-saving medicines," said Roberta Massender, Vice-Chair of the Pulmonary Hypertension Association of Canada and President of the British Colombia Pulmonary Hypertension Society.

Results from another major clinical trial (CHEST) showed that Adempas is the first ever drug to provide statistically significant clinical improvement in patients with inoperable CTEPH or persistent or recurrent CTEPH after surgical treatment 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.⁴ Adempas also significantly improved exercise capacity measured by a six-minute walk distance (6MWD).⁴

Long-term trials of Adempas in PAH and CTEPH are ongoing, and interim results show that safety and tolerability as well as efficacy (change in 6MWD) are sustained over one year.^13,14

About Pulmonary Hypertension (PH)
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.^6,7 Patients with PH develop a markedly decreased exercise capacity and a reduced quality of life.¹⁰ The most common symptoms of PH include shortness of breath, fatigue, dizziness and fainting, all of which are worsened by exertion.^8,9 As the symptoms of PH are non-specific, diagnosis can be delayed by as much as two years.^10,15,16 Early diagnosis and accurate identification of the PH category is essential as a delay in treatment initiation can have a negative impact on survival.^10,17 Continuous treatment monitoring is vital to ensure that patients receive optimal care for their particular PH category and stage of disease.¹⁰

There are five different PH categories and each can affect the patient in a different way. Every patient may have a different etiology and manifestation of PH.^10,18,15 For the best chance of success, patients need to be treated at an expert PH centre.10,19  In Canada, there are 15 recognized expert PH centres across the country.²⁰

About Pulmonary Arterial Hypertension (PAH)
PAH, one of the five categories of PH, is a progressive and life-threatening disease in which the blood pressure in the pulmonary arteries is significantly increased due to vasoconstriction and which can lead to heart failure and death.^6,10 PAH is characterized by morphological changes to the endothelium of the artery of the lungs causing remodeling of the tissue and vasoconstriction. As a result of these changes, the blood vessels in the lungs are narrowed, making it difficult for the heart to pump blood through to the lungs.^6,7 PAH is a rare disease and affects an estimated 15 to 52 people per million.^6,7,2 It is more prevalent in younger women than men.² In most cases, PAH has no known cause and, in some cases, it can be inherited.^9,2

In spite of several pharmacological treatment options for PAH having been available for over a decade, the prognosis for these patients has remained poor and new treatment options are needed. Currently, mortality of PAH patients remains high and is still 15% within one year of diagnosis and 32% within three years of diagnosis.¹¹

About Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
CTEPH is a rare, progressive and life-threatening disease and a category 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.^10,18

CTEPH may evolve after prior episodes of acute pulmonary embolism, but the mechanism is not yet completely understood.¹⁸ 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.¹⁸ 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.^18,21,22 These patients need an effective pharmacological treatment.²²

About Adempas®
Adempas (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.^23,24 Adempas is being investigated as a novel and specific approach to treat different categories of PH.^23,24 sGC is an enzyme found in the cardiopulmonary system and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme enhances production of the signaling molecule cyclic guanosine monophosphate (cGMP). cGMP plays an important role in regulating vascular tone, proliferation, fibrosis, and inflammation.²⁵

PH is associated with endothelial dysfunction, impaired synthesis of NO and insufficient stimulation of sGC.²³ Adempas has a unique mode of action - it sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Adempas also directly stimulates sGC via a different binding site, independently of NO.^23,24,25 Adempas, as a stimulator of sGC, addresses the issue of NO deficiency by restoring the NO-sGC-cGMP pathway, leading to increased generation of cGMP.²³

With its novel mode of action, Adempas has the potential to overcome a number of limitations of currently approved PAH therapies, including NO dependence.²³

It is also the first drug which has shown clinical benefits in CTEPH, where no indicated pharmacological treatment was previously available.^1,3

About Bayer in Canada
Bayer Inc. is a Canadian subsidiary of Bayer AG and the corporate headquarters for the Canadian operations.  Founded in 1863, 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 Bayer CropScience Inc. operates out of its head office in Calgary, AB. Together with its material science business, Bayer improves the quality of life for Canadians through products that fight disease, protect crops and animals, and provide high-performance materials for numerous daily life uses. 

With more than 1,300 employees across the country, in 2013, Bayer had sales of $1.6 billion and invested $61 million in research and development in Canada. Globally, Bayer AG had sales of €40.2 billion and invested €3.2 billion in research and development.

For more information about Bayer, 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} Adempas® Product Monograph, March 04, 2014

² Peacock AJ, Murphy NF, McMurray JJ, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. Eur Respir J. 2007 Jul;30(1):104-9.

³ Mayer E. Surgical and post-operative treatment of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2010;19(115):64-67.

⁴ Ghofrani HA, D'Armini AM, Grimminger F et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013;369(4):319-329.

⁵ Ghofrani HA, Galie N, Grimminger F et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 2013;369(4):330-340.

⁶ Rosenkranz S. Pulmonary hypertension: current diagnosis and treatment. Clin Res Cardiol 2007;96(8):527-541.

⁷ Macchia A, Marchioli R, Marfisi R et al. A meta-analysis of trials of pulmonary hypertension: a clinical condition looking for drugs and research methodology. Am Heart J 2007;153(6):1037-1047.

⁸ McKenna SP, Doughty N, Meads DM, Doward LC, Pepke-Zaba J. 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(1):103-115.

⁹ PHA UK. What is pulmonary hypertension? http://www.phassociation.uk.com/what_is_ph, 2013.

¹⁰ Galie N, Hoeper MM, Humbert M 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(20):2493-2537.

¹¹ Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest 2012;142(2):448-456.

¹² Girgis RE. Emerging drugs for pulmonary hypertension. Expert Opin Emerg Drugs 2010;15(1):71-85.

¹³ Simonneau G, D'Armini AM, Ghofrani HA et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH): a phase III long-term extension study (CHEST-2). 5th World Sympsoium on Pulmonary Hypertension, Nice, France, 27 February - 1 March; 2013.

¹⁴ Rubin LJ, Galie N, Grimminger F et al. Safety and efficacy of riociguat for the long-term treatment of pulmonary arterial hypertension (PAH) in the phase III PATENT-2 long-term extension study. American Thoracic Society International Conference, Philadelphia, PA, USA, 17-22 May; 2013.

¹⁵ Armstrong I, Rochnia N, Harries C, Bundock S, Yorke J. The trajectory to diagnosis with pulmonary arterial hypertension: a qualitative study. BMJ Open 2012;2(2):e000806.

¹⁶ Peacock AJ. Treatment of pulmonary hypertension. BMJ 2003;326(7394):835-836.

¹⁷ Vachiery JL, Yerly P, Huez S. How to detect disease progression in pulmonary arterial hypertension. Eur Respir Rev 2012;21(123):40-47.

¹⁸ Ali JM, Hardman G, Page A, Jenkins DP. Chronic thromboembolic pulmonary hypertension: an underdiagnosed entity? Hosp Pract (1995) 2012;40(3):71-79.

¹⁹ Ghofrani HA, Distler O, Gerhardt F 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.

²⁰ PHA Canada. Canadian Medical Centres Specializing in the Treatment of PH. http://www.phacanada.ca/en/patients/clinical-directory, 2014.

²¹ Condliffe R, Kiely DG, Gibbs JS et al. Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 2008;177(10):1122-1127.

²² Freed DH, Thomson BM, Berman M et al. Survival after pulmonary thromboendarterectomy: effect of residual pulmonary hypertension. J Thorac Cardiovasc Surg 2011;141(2):383-387.

²³ Ghofrani HA, Voswinckel R, Gall H et al. Riociguat for pulmonary hypertension. Future Cardiol 2010;6(2):155-166.      

²⁴ Grimminger F, Weimann G, Frey R et al. First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J 2009;33(4):785-792.

²⁵ Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation 2011;123(20):2263-2273.

SOURCE: Bayer Inc.

Marija Mandic, 416-240-5376, [email protected]