A relief for heart and lung - from nitroglycerin to innovative therapies

(f.l.t.r.) Dr. med. Reiner Frey, Prof. Dr. rer. nat. habil. Johannes-Peter Stasch, Prof. Dr. med. Ardeschir Ghofrani

Prof. Dr. med. Ardeschir Ghofrani* (Spokesperson)
Dr. med. Reiner Frey
Prof. Dr. rer. nat. habil.
Johannes-Peter Stasch

Bayer Pharma AG, Wuppertal
*Justus Liebig University Giessen

People who suffer from pulmonary hypertension are forced to accept that their quality of life is severely limited. Many patients die within a few years of diagnosis. Is there any way to stop this from happening?

Prof. Dr. Ardeschir Ghofrani, Dr. Reiner Frey and Prof. Dr. Johannes-Peter Stasch have developed an innovative drug that is effective in treating two forms of the serious and progressive disease. In the course of their work, the researchers discovered a mechanism of action that directly affects the molecular processes in the cardio-pulmonary system - and in the future could also be used to treat a number of other diseases. Johannes-Peter Stasch is an honorary professor for pharmaceutical research at the University of Halle-Wittenberg and was the senior fellow in cardiovascular research at Bayer Pharma AG. Reiner Frey also worked at Bayer as a senior fellow in clinical pharmacology. Ardeschir Ghofrani is head of the Pulmonary Hypertension Clinic at University Clinic Giessen und Marburg and is medical director of the Kerckhoff Clinic in Bad Nauheim.

The use of nitroglycerin in the treatment of cardiovascular diseases began 130 years ago. Initially used as an explosive, it is administered to treat angina pectoris. In the body, it releases nitric oxide (NO) that dilates blood vessels and lowers blood pressure, but it also degrades rapidly.

The body also produces NO. Patients with pulmonary hypertension do not produce enough NO and the pressure in the pulmonary arteries rises. Affected persons suffer from shortness of breath which makes everyday activities such as climbing stairs or walking longer distances difficult. Added to this are fatigue and circulatory problems that may result in fainting spells. Untreated, patients usually die of heart failure within a few years. To date, treatments to relieve pulmonary hypertension are available only for two types of the disease. Restoration of health can only be achieved for one form by means of an operation and the other form cannot be treated - a drug therapy has still not been found for the first type. Until now.

NO acts together with an enzyme that imparts its vasodilatory effect to the cells: "soluble guanylate cyclase" (sGC). Bayer researchers discovered a way to stimulate sGC independent of NO in 1994. Together with scientists from Giessen, they proved that this was an effective and promising way to treat pulmonary hypertension. Riociguat, the first active agent suitable to treat the disease, was synthesized for the first time in 2000. Thanks to its dual mechanism of action, Riociguat increases the effects of NO or replaces it to stimulate sGC to lower blood pressure in the lungs.

On the basis of this discovery, BAYER has developed the drug ADEMPAS® that is now approved in over 50 countries. It is effective in treating the symptoms of the disease and slows its progression. In the USA, it has been approved for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) - a form of the disease that has never before able to be treated by medication - if an operation is not possible or has been unsuccessful. The drug has also proven effective for certain types of pulmonary arterial hypertension (PAH). The drug was approved in the European Union in March 2014. Ongoing long-term studies have since documented that it is effective and safe over a period of up to two years. Other active agents from this class of substances are meanwhile being clinically tested for other diseases, e.g. in the treatment of chronic heart failure (cardiac insufficiency).

In addition to the great medical benefits, the drug also has vast commercial potential. Forecasts suggest annual turnover in excess of Euro 500m in the coming years. The development of the new drug for the treatment of pulmonary hypertension is exemplary of successful pharmaceutical innovation in Germany. The pharmacological principle was discovered in Germany. The active substance was developed and tested in Germany. The drug is produced in Germany. This has resulted in and will create numerous new jobs.

The right to nominate outstanding achievements for the Deutscher Zukunftspreis is incumbent upon leading German institutions in science and industry as well as foundations.

The project "A relief for heart and lung - from nitroglycerin to innovative therapies" was nominated by acatech – National Academy of Science and Engineering e.V..

Resume

Prof. Dr. med. Ardeschir Ghofrani

07.06.1967
Born in Clausthal-Zellerfeld
1986
Abitur – diploma from German secondary school qualifying for university admission or matriculation
1986
Study of chemistry, RWTH Aachen
1987 – 1994
Medical school Justus-Liebig-University Giessen
1994 – 2003
Resident, Medical Clinic II, University Hospital Giessen
2003
Senior house officer, Medical Clinic II, University Hospital, Head of Pulmonary Hypertension Outpatient Clinic
2004
Specialist Internal Medicine (medical licence)
2005
Habilitation in Internal Medicine, topic „Inhaled Prostanoids and Phosphodiesterase-5-Inhibitors for the Treatment of Pulmonary Hypertension“
2006
Associate Professor for Internal Medicine, JLU Giessen
since 2007
„Area Leader“ at the Excellence Cluster Cardiopulmonary System (ECCPS)
since 2007
Member of the Steering Committee of the ECCPS
since 2009
Full Professor „Chair for Pulmonary Vascular Research“ JLU Gießen, Germany
since 2009
Head of Department Pneumology, Kerckhoff-Clinic Bad Nauheim, Germany
since 2009
Medical Executive Director, Kerckhoff-Clinic Bad Nauheim, Germany
since 2013
Professor for Pulmonary Vascular Medicine, Department of Medicine, Imperial College London, UK (part time)

Honors:

2002
“Travel Award” of the American Thoracic Society; Pulmonary Circulation Assembly
2002
Francois Brenot Award of the European Respiratory Society “For promising young investigator in pulmonary vascular sciences”
2004
Award of the “René-Baumgart-Foundation”
2004
Paul-Martini-Prize

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Dr. med. Reiner Frey

06.10.1949
Born in Nagold
1968
Abitur, High School, Nagold
1971 – 1977
Medical Studies, Eberhard Karls University Tübingen
1977 – 1978
Medicinal Assistant at the department „anesthesia, surgery and internal medicine”
1978
License to practice medicine („Approbation“)
1978
Ph. D., at the chair and department for pediatric cardiology at the Eberhard Karls University Tübingen,
Topic: „Echocardiographic findings in the infantile Idiopathic Hypertrophic Subaortic Stenosis“
1979 – 1986
Medical specialists training in pediatrics and pediatric cardiology at the University children’s hospital in Tübingen
1986
Medical specialist approval in pediatrics and pediatric cardiology
1987
Qualification in emergency medical services
1988
Additional qualification in sports medicine
1986 – 1988
Resident physician at the Department for Internal Medicine at the county hospital in Nagold
1989 - 2015
International Clinical Project Lead, Department of Clinical Pharmacology, Bayer AG, Wuppertal
since 1998
Clinical development of sGC-stimulators
2004
Start of the clinical development of Riociguat
2010
Chief Scientist, Bayer HealthCare
since 2015
Senior Consultant

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Prof. Dr. rer. nat. habil. Johannes-Peter Stasch

18.08.1954
Born in Hessisch-Oldendorf
1965 – 1973
Schiller High School, Hameln, “Abitur” examination
1973 – 1978
Studies Leibniz University Hannover and Julius-Maximilians-University Würzburg Degree dissertation, Physical Chemistry Department, Julius-Maximilians- University, Würzburg
1978 – 1980
Alternative civilian service Neurochemistry Department, Würzburg University Hospital
1980 – 1983
Doctorate Dr. rer. nat., Neuropharmacology Department, Würzburg University Hospital, and Inorganic Chemistry Department, Bielefeld University,
Topic: Sila-piperidines and silylated piperidines with potential anti-Parkinson activity – syntheses, receptor binding studies and influences on the chemical signal transmission in the central nervous system”.
1980 – 1983
Pharmacy studies Julius-Maximilians- University, Würzburg
1983 – 1984
Internship Raths-Apotheke pharmacy, Hameln, and Pharma Hameln GmbH
1984
License to practice pharmacy
1984
Laboratory head at Bayer AG’s Institute for Cardiovascular Research in Wuppertal,
Research Scientist
1985
Senior Research Scientist Bayer AG Wuppertal
1990
Principal Research Scientist
1991
Qualification as a specialist in drug product information
1991
Authorization to train students in drug product information
1995
Research Fellow
2003
Qualification to teach pharmacology, Martin-Luther-University, Halle-Wittenberg University, associate professor
2004
Senior Research Fellow, Bayer AG, Wuppertal
2008
Chief Scientist, Bayer HealthCare
2010
Honorary professor of Industrial Drug Discovery and Development
2015
Senior Consultant Bayer AG Wuppertal

Honors:

2008
European Federation of Pharmaceutical Industries and Associations (EFPIA)
“Achievements in fundamental research in cardiology”
2008
Otto Bayer Medal
2013
Elected a member of Deutsche Akademie der Naturforscher Leopoldina - Nationale Akademie der Wissenschaften

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Contact

Spokesperson

Prof. Dr. Ardeschir Ghofrani
Universitätsklinikum Gießen
Klinikstraße 36
35392 Gießen
Phone: + 49 (0) 641 / 99 42 422
E-Mail: Ardeschir.Ghofrani@innere.med.uni-giessen.de
www.uni-giessen.de

Press

Dr. Katharina Jansen
Brand, Communication & Government Relation, Science & Research
Bayer AG
Phone: +49 (0) 214 / 30 33 243
E-Mail: katharina.jansen@bayer.com
www.bayer.com

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