New AbESTT Data Show Significant Benefits of Reopro-R- in Ischaemic Stroke.

Business Editors

VALENCIA, Spain--(BUSINESS WIRE)--May 23, 2003

Two New Presentations at the European Stroke Conference in

Valencia Show That Reopro Improves Recovery from Ischaemic 

Stroke and May Extend the Current Treatment Window

ReoPro(R) (abciximab) significantly improves the recovery of patients with ischaemic stroke when administered up to six hours after stroke onset, according to new data from AbESTT (Abciximab in Emergent Stroke Treatment Trial) presented today at the 12th European Stroke Conference in Valencia, Spain.

The presentation, by Professor Werner Hacke, Universitatsklinikum Heidelberg, Germany, during today's 'New Clinical Trial Results' session, was based on modified Rankin Scale (mRS) responder data, an analysis of stroke recovery that takes into account the initial stroke severity. In his presentation, Prof. Hacke defined mRS responders as patients who make a substantial recovery in terms of functioning (measured on the mRS scale of 0 - 6, where 0 represents normal function), compared to the original extent of the underlying neurological damage caused by the stroke (measured on the National Institutes of Health Stroke Scale, or NIHSS). Three months after suffering a stroke, significantly more patients treated with ReoPro within 6 hours of stroke onset achieved the status of mRS responder compared to placebo (36.5% vs 27%; P = 0.041).

"Achieving an mRS score of 1 at three months after stroke onset represents a poor outcome for a patient suffering a mild stroke, whereas a mRS score of 2 at three months would be a good recovery for a severe stroke patient," said Prof. Hacke. "Taking into account the severity of stroke when assessing recovery makes clinical sense, and these AbESTT results demonstrate a significant therapeutic benefit of ReoPro in patients with ischaemic stroke."

The recovery of normal or near-normal neurological function is a key goal in stroke treatment1, but physicians currently rely primarily on rehabilitation techniques to achieve this, because the only approved treatment available for ischaemic stroke must be taken within three hours of stroke onset. Stroke symptoms are not always easily recognisable, and the majority of patients do not reach a hospital within this time window. A second presentation, to be made by Professor Antoni Davalos, Hospital Josep Trueta, Spain, on Saturday suggests that ReoPro may extend that time window. Prof. Davalos will report that significantly more AbESTT patients treated with ReoPro within five hours of the onset of stroke achieved mRS scores of 0 or 1 (normal or near-normal function) than placebo (53.9% vs 34.6%; P = 0.013).

Previous data from AbESTT confirmed the safety of ReoPro in ischaemic stroke, and demonstrated trends suggesting ReoPro may increase recovery and reduce mortality2-3. ReoPro's current indication is for prevention of ischaemic cardiac complications in patients undergoing coronary angioplasty.

About the AbESTT Study

AbESTT was a randomised, double-blind, placebo-controlled Phase IIb trial of ReoPro in 400 adult patients with acute ischaemic stroke who were able to be treated within six hours of stroke onset. Analysis of mRS responders was a prespecified secondary analysis, with 'responders' defined as mRS at 3 months = 0 if NIHSS score at baseline was 4-7, mRS at 3 months = 0-1 if NIHSS score at baseline was 8-14, and mRS at 3 months = 0, 1, or 2 if NIHSS score at baseline was 15-22. A post-hoc analysis revealed that patients treated with abciximab within a five-hour time window had a larger therapeutic benefit as compared to patients treated more than five hours after symptom onset; i.e., 53.9% of patients treated within five hours with abciximab achieved mRS of 0 or 1 at 3 months versus 34.6% treated with placebo (OR 2.21, 95% CI 1.18-4, 13, p = 0.013). If treatment was started after five hours, 43.4% of abciximab treated patients and 44.1% of placebo treated patients achieved mRS of 0 or 1 at 3 months (OR 1.03, 95% CI 0.61 - 1.73, p = NS).

The AbESTT investigators previously reported on safety and a first set of efficacy findings. The co-primary endpoints were fatal or symptomatic intracranial haemorrhage (ICH) rates at day five or discharge (whichever was sooner), and the clinical outcome at 3 months measured on the mRS. ICH rates were 3.5 percent for ReoPro, compared with 1 percent in the placebo arm, although none of these was fatal. Asymptomatic ICH rates were slightly lower in the ReoPro arm than in the placebo arm (12.3 percent vs. 16.6 percent). The co-primary efficacy end points showed trends towards a better functional outcome.

About Stroke

Stroke causes around 10 percent of all deaths in industrialised countries4 and more than 5 million deaths a year worldwide, including 1.5 million a year in Europe alone5. Around 80 percent of strokes are ischaemic6 - caused by a thrombus (blood clot) blocking a blood vessel in the brain and cutting off blood supply to part of the brain. Stroke is also a leading cause of long-term disability, and currently only half to two-thirds of patients surviving stroke regain independence7.

About ReoPro

ReoPro(R) (abciximab) was developed by Centocor of Malvern, Pennsylvania, USA, and is manufactured by Centocor, B.V., in Leiden, the Netherlands. Eli Lilly and Company markets and distributes the product worldwide except in Japan. The companies have announced plans to conduct a large Phase III trial to confirm the findings from AbESTT.

ReoPro is a glycoprotein IIb/IIIa inhibitor and is indicated for prevention of ischaemic cardiac complications in high-risk patients undergoing coronary angioplasty. In these settings, ReoPro prevents complications associated with thrombi (blood clots), and has been proven to reduce mortality, repeat heart attacks, or repeat PCI. ReoPro (abciximab) has the potential to increase the risk of bleeding, particularly in the presence of anticoagulation, e.g., from heparin, other anticoagulants, or thrombolytics. In the EPILOG trial, the incidence of major bleeding was similar to placebo levels. Similar bleeding rates were achieved in the more recent EPISTENT trial.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs.

About Centocor, Inc.

Centocor is a leading biopharmaceutical company that creates, acquires and markets cost-effective therapies that yield long-term benefits for patients and the health care community. Its products, developed primarily through monoclonal antibody technology, help physicians deliver innovative treatments to improve human health and restore patients' quality of life. Centocor is a wholly owned subsidiary of Johnson & Johnson, a worldwide leader of health care products.

Certain of the matters discussed herein with respect to clinical studies and Centocor's and Lilly's products may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on current expectations, estimates and projections about the industry, management beliefs and certain assumptions made by management. Investors are cautioned that matters subject to forward-looking statements involve risks and uncertainties, including economic, competitive, governmental, technological and other factors discussed in the two companies' respective filings with the Securities and Exchange Commission, which may affect the business and prospects of the two companies. More specifically, there can be no assurance that this product will achieve commercial success or that competing products will not preempt any market opportunity that might exist for the product. For further discussion of risk factors, please see the companies' filings with the U.S. Securities and Exchange Commission. Neither company undertakes any duty to update forward-looking statements.

ReoPro(R) is a registered trademark of Centocor, Inc. and is marketed by Eli Lilly and Company.

References

1. Gomez,C.R., Orr,S.C. & Soto,R.D. Neuroendovascular Rescue: Interventional Treatment of Acute Ischemic Stroke. Curr. Treat. Options. Cardiovasc. Med. 4, 405-419 (2002).

2. Abciximab in acute ischemic stroke: a randomized, double-blind, placebo- controlled, dose-escalation study. The Abciximab in Ischemic Stroke Investigators. Stroke 31, 601-609 (2000).

3. Results from the Abciximab in Emergent Stroke Treatment Trial, presented by Harold Adams at the 28th International Stroke Conference, Phoenix, USA, 2003.

4. Khaw,K.T. Epidemiology of stroke. J. Neurol. Neurosurg. Psychiatry 61, 333-338 (1996).

5. The World Health Organization. The World Health Report 2001. Mental Health: New Understanding, New Hope. 2002.

Ref Type: Report

6. Del Zoppo,G.J. et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann. Neurol. 32, 78-86 (1992).

7. Brott,T. & Bogousslavsky,J. Treatment of acute ischemic stroke. N. Engl. J. Med. 343, 710-722 (2000).