Eli Lilly and Company logo. (PRNewsFoto) INDIANAPOLIS, IN USA
		Sankyo Co., Ltd. (PRNewsFoto) SAN DIEGO, CA USA

    INDIANAPOLIS, Ind., and TOKYO, Japan, Oct. 17 /PRNewswire-FirstCall/ --
Eli Lilly and Company (NYSE: LLY) and Sankyo Co., Ltd. announced today data
results from three early-phase, cross-over studies demonstrating that all
subjects responded to prasugrel, an investigational antiplatelet agent, while
22 to 43 percent of the same subjects did not respond to clopidogrel
(Plavix(R)), as measured by objectively defined parameters for inhibition of
platelet aggregation.  The data were presented at the Cardiovascular Research
Foundation's (CRF) 17th Annual Transcatheter Cardiovascular Therapeutics (TCT)
scientific symposium, in Washington, D.C.
    "We are very encouraged by the consistent response rate seen with
prasugrel across these three studies," said Govinda Weerakkody, Ph.D.,
Principal Research Scientist at Eli Lilly and Company.  "We are studying
whether more reliable inhibition of platelet aggregation could have an
important effect on patient outcomes."  Eli Lilly and Sankyo Co., Ltd. are
developing prasugrel as a potential treatment for patients who have suffered a
heart attack or unstable angina (heart-related chest pain).
    Antiplatelet agents are used both acutely and as maintenance therapy to
inhibit platelet activation and aggregation that occurs in diseased arteries
and in response to invasive procedures such as percutaneous coronary
intervention (PCI), a procedure to open blockages in heart arteries, and
includes the use of coronary stents.  Antiplatelet agents prevent platelets
from clumping or sticking together, which can cause formation of blood clots
and lead to heart attack or stroke.  Recent studies suggest that a
relationship may exist between a poor platelet response to antiplatelet agents
in individual patients and poor clinical outcomes, which manifest as major
adverse cardiovascular events, including heart attacks.(1,2,3)

    About the Data
    The pooled analysis, "Clopidogrel Nonresponders: A Comparison With
Prasugrel (CS-747, LY640315), a Novel Thienopyridine P2Y12 Receptor
Antagonist," is based on the results of three, single-center, two-way cross-
over clinical pharmacology studies.(4,5,6)  One hundred and twelve healthy
volunteers aged 18-65 years old were randomized to receive either a 60 mg
loading dose of prasugrel or the approved 300 mg loading dose of clopidogrel
in a 2-way cross-over design.  Adenosine diphosphate (ADP) was used to induce
platelet aggregation in samples of subjects' blood.  Inhibition of platelet
aggregation (IPA) and the change in maximum platelet aggregation (MPA) from
baseline were evaluated at both 4-5 and 24 hours after the medication was
administered.
    Nonresponders were objectively defined as subjects achieving less than 25
percent IPA or a difference of less than 20 percent in MPA in response to 5
micromolar adenosine diphosphate (ADP), and less than 20 percent IPA or a
difference of less than 15 percent in MPA in response to 20 micromolar ADP.
These thresholds represent levels of platelet inhibition that are more
consistent with a placebo than that of an active antiplatelet agent.
    All subjects responded effectively to a loading dose of prasugrel 60 mg.
However, when the same subjects were administered 300 mg of clopidogrel, 22
percent were nonresponders based on IPA in response to 5 micromolar ADP
(p < .001) and 43 percent were nonresponders based on IPA in response to 20
micromolar ADP (p < .001).

    Current Clinical Research with Prasugrel
    A Phase III clinical study with prasugrel -- TRITON-TIMI 38 -- is under
way.  This head-to-head study will compare the effects of prasugrel with
clopidogrel in up to 13,000 patients with acute coronary syndrome who suffer a
heart attack or have unstable angina and are to undergo PCI.  The primary
focus of the study is to compare the two agents' ability to prevent heart
attack, stroke and death in patients who undergo PCI.  The secondary focus is
to look at the impact on bleeding, hospitalization for recurrent heart-related
chest pain (ischemia) or the need for additional procedures to restore blood
flow (urgent target revascularization).  It is anticipated that the TRITON
TIMI-38 study should be completed in early 2007 with regulatory submissions to
follow in the second half of 2007.
    "Early studies have revealed the promise of prasugrel as an antiplatelet
therapy," said Jeffrey Warmke, Ph.D., Sankyo's Executive Director of Global
Project Management.  "We look forward to receiving the results of the current
Phase III trial to determine whether prasugrel provides additional clinical
benefits for patients with acute coronary syndrome."
    Cardiovascular disease is the leading cause of death in the U.S. and
worldwide, killing 17 million people each year.(7)  Acute heart attacks and
unstable angina, called acute coronary syndrome (ACS), affect more than
942,000 Americans each year.  Despite current medical interventions, 300,000
people experience recurrent heart attacks and 500,000 people die from heart
attacks annually in the U.S.(8)

    About Prasugrel
    Prasugrel is an investigational antiplatelet agent designed to prevent
platelet activation and aggregation by blocking adenosine diphosphate
receptors on the platelet surface.  This novel oral compound was discovered by
Sankyo and Ube Industries, Ltd. (TSE: 4208).  It is being investigated as a
potential treatment for higher risk patients with acute coronary syndrome who
undergo percutaneous coronary intervention (PCI).

    About Lilly
    Lilly, a leading innovation-driven corporation, is developing a growing
portfolio of first-in-class and best-in-class 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.  Building on
the strong foundation of ReoPro, Lilly is in the process of building a robust
cardiovascular pipeline.  Lilly has multiple cardiovascular drugs in that
pipeline -- in every stage from pre-clinical and Phase I to the Phase III
trials for prasugrel.
    Additional information is available at http://www.lilly.com .
    P-LLY

    About Sankyo
    Sankyo Co., Ltd. of Tokyo, one of Japan's largest pharmaceutical
companies, has a long history of discovering new classes of drugs, including
the statin class of lipid-lowering drugs.  Beginning with the discovery of the
first statin, mevastatin, and the co-discovery of lovastatin, the first statin
to be marketed, Sankyo has been a pioneer in the cardiovascular disease arena.
Additionally, Sankyo discovered, developed, manufactures and markets
pravastatin sodium and olmesartan medoxomil, an angiotensin II receptor
blocker (ARB).  Sankyo Co., Ltd. and Daiichi Pharmaceutical Co., Ltd.,
recently announced the integration of the organizations, creating the second-
largest drug company in Japan.  For further information about Sankyo and its
products, log on to http://www.sankyo.co.jp/english/ .

    This press release contains certain forward-looking statements about the
potential of the investigational compound prasugrel (CS-747, LY640315) and
reflects Lilly's current beliefs.  However, as with any pharmaceutical product
under development, there are substantial risks and uncertainties in the
process of development and regulatory review.  There is no guarantee that the
product will receive regulatory approvals, or that the regulatory approval
will be for the indication(s) anticipated by the company.  There is also no
guarantee that the product will prove to be commercially successful.  For
further discussion of these and other risks and uncertainties, see Lilly's
filing with the United States Securities and Exchange Commission.  Lilly
undertakes no duty to update forward-looking statements.

    Plavix(R) is a registered trademark of Sanofi-Synthelabo Inc.

    (1) Barragan, P., Bouvier, J. L., Roquebert, P. O., Macaluso, G., Commeau,
P., Comet, B., Lafont, A., Camoin, L., Walter, U., and Eigenthaler, M.
Resistance to thienopyridines: clinical detection of coronary stent thrombosis
by monitoring of vasodilator-stimulated phosphoprotein phosphorylation.
Catheter Cardiovasc Interv 2003; 59: 295-302
    (2) Muller, I., Besta, F., Schulz, C., Massberg, S., Schonig, A., and
Gawaz, M.  Prevalence of clopidogrel non-responders among patients with stable
angina pectoris scheduled for elective coronary stent placement.  Thromb
Haemost 2003; 89: 783-787
    (3) Matetzky, S., Shenkman, B., Guetta, V., Shechter, M., Bienart, R.,
Goldenberg, I., Novikov, I., Pres, H., Savion, N., Varon, D., and Hod, H.
Clopidogrel resistance is associated with increased risk of recurrent
atherothrombotic events in patients with acute myocardial infarction.
Circulation 2004; 109: 3171-3175.
    (4) A Comparison of Prasugrel (CS-747, LY640315) With Clopidogrel on
Platelet Function in Healthy Male Volunteers; Fumitoshi Asai, Joseph A.
Jakubowski et al.  Presented at American College of Cardiology March 9, 2005
    (5) Inhibition of Platelet Aggregation With Prasugrel (CS-747, LY640315),
A Novel Thienopyridine P2Y12 Receptor Antagonist, Compared With Clopidogrel in
Aspirin-Treated Patients With Atherosclerotic Vascular Disease; Lars
Wallentin, John T. Brandt et al.  Presented at American College of Cardiology
March 8, 2005.
    (6) Superior Responder Rate for Inhibition of Platelet Aggregation With a
60 mg Loading Dose of Prasugrel (CS-747, LY640315) Compared With a 300 mg
Loading Dose of Clopidogrel; John T. Brandt, Christopher D. Payne et al,
Presented at American College of Cardiology March 9, 2005.
    (7) World Health Organization.  The Atlas of Heart Disease and Stroke -
Types of Cardiovascular Disease 2005.
    (8) American Heart Association.  Heart Disease and Stroke Statistics 2005.

     (Logo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO
            http://www.newscom.com/cgi-bin/prnh/20040827/SANKYO )

Link to this page: