Recent Research Shows Significant Benefits in Acute Ischaemic Stroke With Actilyse(R) Beyond Currently Approved Three Hour Treatment Window

Ingelheim, Germany (ots/PRNewswire) -

- For Healthcare Media Outside the U.S.A., Canada, and Japan

- Favourable Safety and Efficacy Profile of Actilyse(R) Confirmed
by ECASS 3 Study Investigating Treatment in an Extended Time Window
up to 4.5 Hours After Symptom Onset

First results from ECASS 3 (European Cooperative Acute Stroke
Study) were presented today at the 6th World Stroke Congress in
Vienna, Austria, showing that treatment with Actilyse(R) (alteplase)
between 3 and 4.5 hours after stroke onset can improve clinical
outcome. These results were also published today in the New England
Journal of Medicine.(1)

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Importantly, data from the trial show that the safety profile of
Actilyse(R), a recombinant tissue plasminogen activator (rt-PA), when
used in the 3 to 4.5 hour time window is consistent with the safety
profile reported in previous clinical trials that investigated
Actilyse(R) use in the currently approved time window of 0 to 3
hours, including the incidence of haemorrhagic events.(2-6)

ECASS 3, which included 821 patients (418 treated with alteplase
vs. 403 placebo-treated patients), was a randomised, double-blind,
placebo-controlled trial designed to evaluate whether the efficacy
and safety of alteplase were maintained up to 1.5 hours beyond the
standard 3-hour time window.

The study showed that patients treated with alteplase in this
extended time window had a 34 percent improvement in the odds of
having a favourable outcome versus placebo (absolute 7.2%
improvement; p=0.04) as measured by the modified Rankin Scale (mRS
0-1). This finding is important as it demonstrates that alteplase can
increase the likelihood of achieving only minimal or no disability
post-stroke, now shown for the first time beyond 3 hours and up to
4.5 hours.

"Early treatment remains the cornerstone of acute stroke therapy
and it is of paramount importance that patients arriving in stroke
units who are eligible for thrombolysis should be treated without
delay. However, the new ECASS 3 data show that stroke can be
effectively managed also in patients who are unable to reach a stroke
centre within three hours," commented Professor Werner Hacke,
Department of Neurology, Ruprecht-Karls-University of Heidelberg,
Germany, lead study investigator. "The results of the trial show that
a large group of patients currently excluded may benefit in the
future from this therapy."

Furthermore, the ECASS 3 data are complemented by similar
findings from SITS-ISTR (Safe Implementation of Treatments in Stroke
- International Stroke Thrombolysis Registry), an academic-driven
acute stroke registry of thrombolysis for ischaemic stroke, which
were published last week in The Lancet(7). These data, collected in a
real life clinical setting, suggest that patients who are treated
with alteplase in accordance with the current European summary of
product characteristics, but in an extended time window of treatment
initiation between 3 and 4.5 hours after stroke onset(*), can
experience a similar clinical outcome as compared with patients who
are treated earlier.

(*) Actilyse(R) is currently approved for use within the 3 hour
time window.

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.

Notes to Editor

Modified Rankin Scale

The Modified Rankin Scale is a numerical functional assessment
scale used to rank levels of disability after stroke. Patients
receive a score between 0 and 6, where 0 represents no symptoms at
all and higher scores represent increasingly severe disability.(8)

About ECASS 3

ECASS 3 was a randomised, double-blind, multicentre,
placebo-controlled trial of Actilyse(R) in acute ischaemic stroke
where thrombolysis is initiated between 3 and 4.5 hours after stroke
onset. The study, sponsored by Boehringer Ingelheim, was requested by
European authorities to support the licencing of Actilyse(R). ECASS 3
started in July 2003 and was completed in February 2008. The patients
included in the study were in line with the Actilyse(R) indication in
the European Summary of Product Characteristics(6) with the exception
of the time window. A total of 821 patients were recruited in 15
European countries.

About Actilyse(R)

Stroke is a neurological emergency that can affect a specific
area, or sometimes all of the brain. It can be caused by a burst
blood vessel (haemorrhagic stroke) or occur when a vessel is
obstructed by a blood clot (ischaemic stroke). Actilyse(R) (active
ingredient: alteplase), a recombinant tissue plasminogen activator
(rt-PA), is a genetically engineered version of naturally occurring
tissue plasminogen activator, which has the biological function of
removing small clots that routinely form in the bloodstream.
Actilyse(R) is the only drug indicated for thrombolytic treatment of
acute ischaemic stroke within three hours of symptom onset, and is
recommended by international treatment guidelines.(9,10) In line with
the current Actilyse(R) label, patients need to receive the
medication within three hours of the onset of their stroke
symptoms.(6) Alteplase was first approved in 1987 in major countries
across the globe in the indication acute myocardial infarction,
followed by subsequent approvals in the indications pulmonary
embolism and acute ischaemic stroke (registered indications can vary
across the globe).

Actilyse(R) is registered in over 85 countries across the world
and marketed outside North America and Japan by Boehringer Ingelheim.
Alteplase is marketed under the brand name Activase(R) in the U.S.A.
by Genentech, Inc. and in Canada by Roche Canada, where it has been
used extensively for the treatment of acute ischaemic stroke since
1996 and 1999, respectively.

About 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.

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inger-ingelheim.com/corporate/news/information_packs/acutestroke.asp

References

1. Hacke W, et al for the ECASS investigators. Thrombolysis with
alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med
September 2008

2. The National Institute of Neurological Disorders and Stroke
rt-PA Stroke Study Group. N Engl J Med 1995; 333: 1581-7

3. Albers GW, et al. ATLANTIS trial: results for patients treated
within 3 hours of stroke onset. Alteplase Thrombolysis for Acute
Noninterventional Therapy in Ischemic Stroke. Stroke 2002; 33: 493-5

4. Hacke W et al. Association of outcome with early stroke
treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke
trials. Lancet 2004; 363: 768-74

5. Wahlgren N, et al. Thrombolysis with alteplase for acute
ischaemic stroke in the Safe Implementation of Thrombolysis in
Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet
2007; 369: 275-82

6. Actilyse(R) Summary of Product Characteristics 2007. Available
at: http://emc.medicines.org.uk/emc/assets/c/html/DisplayDoc.asp?Docu
mentID=308

7. Wahlgren N, Ahmed N, Dávalos A, et al, for the SITS
investigators. Thrombolysis with alteplase 3-4-5 h after acute
ischaemic stroke (SITS-ISTR): an observational study. Lancet 2008;
published online Sept 15. DOI:10.1016/S0140-6736(08)61339-2

8. Modified Rankin Scale. Internet Stroke Center. Available at
http://www.strokecenter.org/trials/scales/rankin.html Accessed 4 May
2008

9. European Stroke Organisation (ESO) Executive Committee; ESO
Writing Committee. Guidelines for management of ischaemic stroke and
transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25: 457-507

10. Strokeupdate.org. Stockholm: Thrombolysis for acute ischaemic
stroke. Karolinska Stroke Update Consensus Statement 2002. Available
from: http://www.strokeupdate.org/ALLCURRENT/Consensus/Consensus_2002
/Cons_thrombolysis_2002.htm Accessed 4 September 2008

Contact:
Ursula Bardon
Corporate Division Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone +49-61-32-77-2622
E-mail: press@boehringer-ingelheim.com

ots Originaltext: Boehringer Ingelheim
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Contact: Ursula Bardon, Corporate Division Communications, Boehringer
Ingelheim GmbH, 55216 Ingelheim/Germany, Phone +49-61-32-77-2622