/25mg hydrochlorothiazide) Approved by EU Commission

(INGELHEIM, April 15 AsiaNet=연합뉴스)

- For Medical Media, Outside the US only

Boehringer Ingelheim today announced that the European Commission has

granted marketing authorisation of the new powerful strength of their fixed

dose combination antihypertensive drug MicardisPlus(R) 80/25 in all 27 EU

member states. It will be launched in Germany and Denmark in the coming weeks,

followed soon by Ireland, the United Kingdom and the rest of EU, and when

approved also in other countries around the world.

The product is licensed for the treatment of essential hypertension in

patients whose blood pressure is not adequately controlled on MicardisPlus(R)

80/12.5 (80 mg telmisartan/12.5 mg hydrochlorothiazide) or patients who have

been previously stabilized on telmisartan and hydrochlorothiazide separately at

the same dosages (1),(2).

The new strength will be marketed by Boehringer Ingelheim in all 27

countries of the European Union under the brand name MicardisPlus(R) 80/25 Its

co-marketing partners will market the new drug in selected countries under

their own brands.

"The approval of MicardisPlus(R) 80/25 provides physicians with a powerful

new drug for patients with difficult to treat essential hypertension", said Dr

Andreas Barner, Member of the Board of Boehringer Ingelheim and responsible for

Research, Development and Medicine.

European approval of MicardisPlus(R) 80/25 follows the submission of

efficacy and safety data from 12 clinical trials performed in patients with

mild to moderate hypertension. The core clinical development programme

consisted of two consecutive trials designed to demonstrate the superiority of

the fixed dose combination 80 mg telmisartan/25 mg hydrochlorothiazide

(T80/H25) versus 80 mg telmisartan/12.5 mg hydrochlorothiazide (T80/H12.5)(2).

971 patients, who were inadequately controlled for their blood pressure (BP) on

existing antihypertensive treatment, were enrolled in the programme. Treatment

with T80/H25 provided superior diastolic and systolic blood pressure lowering

power(x) after 8 weeks of treatment(1) compared to T80/H12.5. In the

consecutive follow up trial 639 patients (633 patients evaluated for efficacy)

were treated with the T80/H25 for further 6 months. At the end of this

treatment interval the proportion of patients achieving DBP control had

increased from 52.4% to 71.4% (2).

No clinically meaningful differences in the adverse event profiles of

T80/H25 and T80/H12.5 were detected. No specific increased incidence was

identified for all adverse events. No additional specific safety issues have

been identified (1,2). Other studies considered by the EMEA showed clearly

superior clinical benefits for a T80/H25-based treatment compared with 160 mg

valsartan /25 mg hydrochlorothiazide, the market leading ARBs high strength

combination (3).

Landmark trial onTARGET(R) proves cardio & vascular protective effects

of telmisartan

Boehringer Ingelheim continues to explore new strategies to improve

cardiovascular therapy: The results of onTARGET(R) (The ongoing Telmisartan

Alone and in Combination with Ramipril Global Endpoint Trial) with 25,620

patients have recently proven that telmisartan is as protective as the current

gold standard, ramipril, in reducing the risk of cardiovascular death,

myocardial infarction, stroke and hospitalisation for congestive heart failure

in a broad cross section of high-risk cardiovascular patients (4). With 25,620

high-risk patients followed up for up to 6 years onTARGET(R) was the largest

ARB outcome trial ever. "The onTARGET(R)results have important implications for

the management of patients with cardiovascular diseases. We now have a new

treatment option for high-risk patients which is effective and better

tolerated," comments Professor Salim Yusuf, lead investigator of the

ONTARGET(R) Trial Programme and Director of the Population Health Research

Institute at McMaster University, Hamilton, Canada.

Evidence for renal protective effects of telmisartan

Further evidence of the exceptional properties of telmisartan has already

been seen in previous trials. In 2007, the AMADEO(R) trial showed that

telmisartan achieved significantly greater reduction in proteinuria compared

with the ARB losartan beyond blood pressure reduction effects, demonstrating

the potential for renal protection with telmisartan in diabetic patients (5).

Proven powerful antihypertensive efficacy

In addition, in 2006 the PRISMA(TM) trials in hypertensive patients

demonstrated that telmisartan achieved more powerful blood pressure reductions

over the full 24-hour period compared with the ACE-inhibitor ramipril (6),(7).

Please be advised

This release is from Boehringer Ingelheim Corporate Headquarters in

Germany. Please be aware that there may be national differences between

countries regarding specific medical information, including licensed uses.

Please take account of this when referring to the information provided in this

document. This press release is not intended for distribution within the U.S.A.

About telmisartan (Micardis(R)/Kinzal(R)/Pritor(R))

Telmisartan is a modern member of the Angiotensin II Receptor Blocker (ARB)

class and is being investigated in the most ambitious and far-reaching research

programme conducted with an ARB. In the clinical trial programmes onTARGET(R),

PROTECTION(R) and PRoFESS(R), over 58,000 patients have been enrolled to

investigate the cardiovascular protective effects of telmisartan (for more

information please visit http://www.news-landmarktrials.com).

Telmisartan was discovered and developed by Boehringer Ingelheim. Under the

trademarks MICARDIS(R) and MICARDISPLUS(R) (combination with

hydrochlorothiazide) the company markets telmisartan in 84 countries around the

world, including the USA, Japan and European countries. Telmisartan is marketed

in cooperation with Astellas Pharma Inc. in Japan, Bayer HealthCare in Europe

and GlaxoSmithKline in selected markets.

Astellas Pharma Inc. co-promotes telmisartan under the trademark

MICARDIS(R), Bayer HealthCare promotes telmisartan under the brand names

Kinzalmono(R), Kinzalkomb(R) (combination with hydrochlorothiazide), and

Pritor(R) and PritorPlus(R) (combination with hydrochlorothiazide) in markets

across Europe. Pritor(R) and PritorPlus(R) is also marketed by GlaxoSmithKline

in selected markets.

About onTARGET(R)

The onTARGET(R) Trial Programme consists of two randomised, double-blind,

multicentre international trials: the principle trial, onTARGET(R) which has

reported its results on 31 March 2008, and a parallel trial TRANSCEND(R)

(Telmisartan Randomized AssessmeNt Study in ACE-I INtolerant subjects with

cardiovascular Disease), which is planned to be reported later in the year (3).

The treatment arms for the onTARGET(R) Trial were telmisartan 80mg,

ramipril 10mg, and combination therapy with telmisartan 80mg and ramipril 10mg.

In the TRANSCEND(R) trial the treatment arms are telmisartan 80mg or placebo -

both on top of standard blood pressure care, not including an ACE or another

ARB (3).

Patients enrolled in The onTARGET(R) Trial Programme were aged greater than

or equal to 55 years, had a history of coronary artery disease, stroke or

recent (> 7 days, < 1 year) transient ischaemic attack, peripheral vascular

disease, or diabetes mellitus with target-organ damage such as

microalbuminuria, ankle-brachial index < 0.8, or left ventricular hypertrophy

(8).

The onTARGET(R) Trial had a four-fold composite endpoint:

-- cardiovascular death,

-- myocardial infarction,

-- stroke, and

-- hospitalisation for heart failure.

Patients intolerant to ACEs were not eligible for the onTARGET(R) study.

Intolerance to ACE was a requirement for enrolment into TRANSCEND(R).

The sponsor of the onTARGET(R) Trial Programme is Boehringer Ingelheim;

co-funders in selected countries are Bayer HealthCare and GlaxoSmithKline.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading

pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates

globally with 135 affiliates in 47 countries and 39,800 employees. Since it was

founded in 1885, the family-owned company has been committed to researching,

developing, manufacturing and marketing novel products of high therapeutic

value for human and veterinary medicine.

In 2007, Boehringer Ingelheim posted net sales of 10.9 billion euro while

spending one fifth of net sales in its largest business segment Prescription

Medicines on research and development.

For more information please visit http://www.boehringer-ingelheim.com

References

(x) -1.6 mmHg, 95% CI from -2.5 to -0.6 mmHg (p=0.0012)) and -2.7 mmHg,

95% CI from -4.2 to -1.2 mmHg (p=0.0003) respectively

(1) Trials.Boehringer-Ingelheim.com. Boehringer Ingelheim Trial Number

502.480

(2) Trials.Boehringer-Ingelheim.com. Boehringer Ingelheim Trial Number

502.491

(3) White WB, Murwin D, Chrysant SG, Koval SE, Davidai G, Guthrie R. Blood

Press Monit. 2008 Feb;13(1):21-27

(4) The onTARGET Investigators. Telmisartan, ramipril, or both in patients

at high risk for vascular events. N Eng J Med. Published online

31 Mar 2008

(5) Bakris G, et al. Influence of glycemic control on proteinuria in

patients with type 2 diabetes and overt nephropathy and hypertension:

results of the AMADEO trial. 67th Sci Sess of the American Diabetes

Association (ADA), Chicago, 22 - 26 Jun 2007 (Poster) 2007.

(6) Williams B, et al. The prospective, randomised investigation of the

safety and efficacy of telmisartan versus ramipril using ambulatory

blood pressure monitoring (PRISMAI). J Hypertens 2006; 24:193-200.

(7) Lacourciere Y, et al. A multicenter, 14-weeks study of telmisartan and

ramipril in patients with mild to moderate hypertension using

ambulatory blood pressure monitoring. Am J Hypertens 2006; 19:104-12

(8) The onTARGET/TRANSCEND Investigators. Rationale, design, and baseline

characteristics of 2 large , simple, randomized trials evaluating

telmisartan, ramipril, and their combination in high-risk patients:

The ongoing Telmisartan Alone and in combination with Ramipril Global

Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE

iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND)

trials Am Heart J 2004; 148(1):52-61.

SOURCE: Boehringer Ingelheim GmbH

CONTACT: Dr. Reinhard Malin of CD Communications

for Boehringer Ingelheim GmbH,

+49-6132-77-90815,

Fax: +49-6132-77-66-01,

press@boehringer-ingelheim.com

(끝)

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