Boehringer Ingelheim affirms safety of telmisartan with an analysis of 50,000
patients and strongly disagrees with the publication of Sipahi et al in
Lancet Oncology June 2010

- For Medical Media Only -

BURLINGTON, ON, June 13 /CNW/ - Telmisartan, an angiotensin receptor blocker, is one of the best researched drugs worldwide. It has been studied in clinical trials in more than 50,000 patients. Its positive safety profile has been confirmed also in a market exposure of 34.5 million patient years. Convincing safety data for patients with a high cardiovascular risk were collected in the three long-term outcome trials ONTARGET, PRoFESS and TRANSCEND which followed some of the patients for up to five years. Following rigorous assessment of the data from these studies it was concluded that there was no association with an increased risk of cancer in the telmisartan arms.

Sipahi et al published a meta-analysis in the June issue of Lancet Oncology, claiming that angiotensin receptor blockers (ARBs) used to lower hypertension are associated with a modestly increased risk of new cancer diagnosis. The finding is mainly based on the combination arm of telmisartan and ramipril, an angiotensin converting enzyme (ACE)-inhibitor, and not on the trial arms of each compound separately.

Patient health and safety is the primary concern of Boehringer Ingelheim. The company continually monitors safety data for all medical products. Boehringer Ingelheim's comprehensive internal safety data analysis of primary data contradicts the conclusions about an increased risk of potential malignancies mentioned by Sipahi et al.

All studies with telmisartan included patients with cardiovascular risk factors due to age and comorbidities. Specifically, in ONTARGET, with more than 25,000 patients, no statistically significant difference with respect to malignancies was observed in patients treated with telmisartan vs ramipril. In TRANSCEND, a 6,000 patient trial, the difference did not reach significance either. In the PRoFESS trial, another large-scale trial with more than 20,000 patients, the telmisartan arm showed fewer cases of malignancies than the placebo arm. Considering the analysis of all three trials an effect of telmisartan on malignancies was not observed.

In ONTARGET, the one treatment arm with a combination of telmisartan and ramipril was associated with a modestly increased risk of malignancies. Consistent with our commitment to transparency, data from ONTARGET, TRANSCEND and PRoFESS have all been published and been widely shared with regulatory authorities since 2008. It should be noted that product labelling for telmisartan does not recommend the combination of telmisartan and ACE-inhibitors such as ramipril.

"Our research efforts have centred on the need to protect patients, especially older patients from cardiovascular risks such as myocardial infarction or stroke. Telmisartan fulfills this need. Doctors and patients appreciate its excellent safety profile. In pre-clinical trials, clinical trials and day-to-day patient exposure with telmisartan, we have not seen any significant finding related to malignancies. Patients should consult with their physicians before making any decision regarding their antihypertensive therapy," said Prof. Dr Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim.

In Canada, telmisartan is indicated to reduce the risk of non-fatal stroke or non-fatal myocardial infarction in patients 55 years or older at high risk of developing major cardiovascular events who cannot tolerate an angiotensin converting enzyme (ACE) inhibitor. High risk of cardiovascular events include evidence of coronary artery disease, peripheral arterial disease, stroke, transient ischemic attack, or diabetes mellitus with evidence of end-organ damage.

Peer-reviewed meta-analyses of aggregate published data like Sipahi et al have their appropriate place in scientific research. However, these analyses have well-recognised limitations, such as combining study summaries rather than analyzing individual patient data.

Telmisartan is one of the most studied anti-hypertensives in clinical trials, which have all been made publically available. It is widely used as medication to lower blood pressure and protect patients against severe cardiovascular events such as myocardial infarction and stroke.

About Cardiovascular Disease in Canada(i)

According to the Heart and Stroke Foundation of Canada, cardiovascular (CV) diseases are defined as diseases and injuries of the cardiovascular system: the heart, the blood vessels of the heart and the system of blood vessels (veins and arteries) throughout the body and within the brain. In Canada, every seven minutes, someone dies from heart disease or stroke. CV disease is responsible for the death of more Canadians than any other disease - more than 30 per cent of all deaths. Heart disease and stroke cost the Canadian economy more than $22.2 billion every year in physician services, hospital costs, lost wages and decreased productivity.

About MICARDIS(R) (telmisartan)

MICARDIS(R) is a modern member of the Angiotensin II Receptor Blocker (ARB) class and has a proven history of controlling hypertension for Canadians. In addition to risk reduction of cardiovascular morbidity, MICARDIS(R) is proven to provide powerful 24-hour blood pressure control, and has a superior side-effect profile, excellent tolerability and better compliance when compared to ramipril.(ii) It is one of the most studied antihypertensives in clinical trials and is widely used with more than five million patient years since its approval. Its safety profile is similar to that of placebo.

Telmisartan was discovered and developed by Boehringer Ingelheim. Under the trademarks MICARDIS(R) and MICARDIS(R) PLUS (combination with hydrochlorothiazide) the company markets it in 84 countries around the world, including the USA, Japan and European countries.

/Notes to editors

Specifically, in ONTARGET, no statistically significant difference with respect to malignancies was observed in patients treated with telmisartan vs ramipril (HR 1.05, 95%CI 0.94, 1.16). In TRANSCEND, the difference did not reach significance either (HR 1.17, 95%CI 0.97, 1.41). In the PRoFESS trial the placebo arm showed more cases of malignancies than the telmisartan arm (HR 0.92, 95%CI 0.79, 1.06). */

About Boehringer Ingelheim (Canada) Ltd.

The Boehringer Ingelheim group is one of the world's 15 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and 41,500 employees.

Founded in 1885, the family-owned company is committed to researching and developing novel products of high therapeutic value for human and veterinary medicine. In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

The Canadian headquarters of Boehringer Ingelheim was established in 1972 and the Research and Development Centre located in Laval, Québec, Canada since 1988. Boehringer Ingelheim (Canada) Ltd. is home to more than 700 employees including 160 scientists across the country.

For more information please visit www.boehringer-ingelheim.ca.

    
    * Data on file

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i. Heart and Stroke Foundation of Canada. Statistics. http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3483991/k.34A8/Statistics.htm#heartdisease (Accessed October 22, 2009)/

ii. Yves Lacourciére, Joel M. Neutel, Gloria Davidai, and Steve Koval, on behalf of the PRISMA II Investigators. A Multicenter, 14-week-Study of Telmisartan and Ramipril in Patients with Mild-to-moderate Hypertension Using ambulatory Blood Pressure Monitoring. American Journal of Hypertension, 19 (1), 2006, 104-12

For further information: Boehringer Ingelheim (Canada) Ltd., Corporate Communications and Corporate Affairs, Derek O'Toole, 5180 South Service Road, Burlington, Ontario, Canada, Tel.: [phone], E-mail: [email protected]