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

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 Canadians(2)
    --  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.

(__________________________________________ )(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, marija.mandic@bayer.com 
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-0- Mar/10/2014 10:59 GMT
 
 
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