Tokyo and Indianapolis, November 4 (ots/PRNewswire) -
- Investigational compound reduces risk of major cardiovascular
events by 19 percent, significantly improves net clinical benefit
despite increased bleeding
In the pivotal Phase III head-to-head TRITON TIMI-38 clinical
trial, the investigational antiplatelet agent prasugrel produced a
highly significant 19 percent reduction in relative risk (p=0.0004)
for the composite endpoint of cardiovascular death, non-fatal heart
attack or non-fatal stroke when compared with clopidogrel
(Plavix(R)/Iscover(R)) in the treatment of patients across the full
spectrum of acute coronary syndrome undergoing percutaneous coronary
A significant reduction in the risk for the composite endpoint
favoring prasugrel (60 mg loading dose/10 mg maintenance dose) over
clopidogrel (300 mg LD/75 mg MD) was observed as early as three days.
The absolute difference in this endpoint continued to increase over
the course of the 15-month, 13,608-patient trial.
In the important subgroup of patients with diabetes, prasugrel
reduced the relative risk of cardiovascular death, non-fatal
myocardial infarction and non-fatal stroke by 30 percent (p<0.001).
In addition, in the key secondary endpoint of stent thrombosis,
prasugrel reduced the recurrence of stent thrombosis (a new clot that
develops at the stent site) by 52 percent (p<0.0001).
TRITON also showed that treatment with prasugrel significantly
reduced the relative risk of cardiovascular death, non-fatal heart
attack and non-fatal stroke by 21 percent in patients with STEMI
(ST-elevation myocardial infarction, or high-risk heart attack)
(p=0.02) and 18 percent in patients suffering from UA (unstable
angina, or chest pain)/NSTEMI (non-STEMI) (p=0.002). In addition,
prasugrel-treated patients experienced a 34 percent decline in urgent
target vessel revascularization (a procedure to reopen blocked
arteries) (p<0.001) and a 42 percent reduction in heart attack with
subsequent death from cardiovascular causes (p=0.02).
While the overall incidence of non-CABG (coronary artery bypass
grafting) bleeding in TRITON was low in both the prasugrel and
clopidogrel treatment groups, prasugrel-treated patients experienced
a statistically significant increase in non-CABG (coronary artery
bypass grafting) major bleeding compared to clopidogrel-treated
patients (2.4 vs. 1.8 percent, or 146 vs. 111 patients, p=0.03),
including higher rates of life-threatening bleeding (1.4 vs. 0.9
percent, or 85 vs. 56 patients, p=0.01). Though infrequent, fatal
bleeding was statistically more frequent among prasugrel-treated than
clopidogrel-treated patients (0.4 percent vs. 0.1 percent, or 21 vs.
five patients, p=0.002). However, death from cardiovascular causes
occurred less frequently among prasugrel-treated patients than
clopidogrel-treated patients (2.1 percent vs. 2.4 percent, or 133 vs.
150 patients, p=0.31), as did all-cause death (3.0 percent vs. 3.2
percent, or 188 vs. 197 patients, p=0.64).
The study identified three distinct patient subpopulations with a
higher risk of major bleeding in both treatment arms - patients who
were 75 years of age or older, weighed less than 60 kg (132 lbs.), or
had a prior history of transient ischemic attack (TIA) or stroke.
Researchers are evaluating pharmacokinetic data from several
prasugrel studies, including TRITON, to determine whether a lower
dose of prasugrel might be appropriate for some patients. Among
patients without any of these risk factors (80 percent of the
13,608-patient TRITON study), there was no significant difference in
major bleeding between prasugrel- and clopidogrel-treated patients (2
percent vs. 1.5 percent, p=0.17).
Based on an analysis using the combined endpoint of all-cause
death, heart attack, stroke and major bleeding, the net clinical
benefit for prasugrel compared with clopidogrel was a significant 13
percent reduction in overall events (12.2 vs. 13.9, p=0.004). In the
subpopulations defined as being at greater risk of bleeding, the net
clinical benefit was not different between prasugrel- and
clopidogrel-treated patients (p=0.43). Without the subpopulations
defined as being at greater bleeding risk, the net clinical benefit
was 20 percent (10.2 vs. 12.5, p<0.001).
Overall, for every 1,000 people treated with prasugrel compared to
clopidogrel in the study, there were 23 fewer heart attacks and an
additional six major bleeding complications.
"Our study provides compelling evidence that the prasugrel regimen
tested is superior to standard dose clopidogrel as an antiplatelet
therapy to support patients undergoing coronary stenting," said
Elliott Antman, M.D., senior investigator with the TIMI Study Group
at Harvard Medical School and director of the Samuel A. Levine
Cardiac Unit at Brigham and Women's Hospital in Boston. "With the
data from TRITON and other studies, we expect to define populations
at particular bleeding risk to help establish clear guidance for
using this promising therapy."
Antman announced the initial study results today at the American
Heart Association's 2007 Scientific Sessions in Orlando, Florida
(abstract 07-LBCT-20660-AHA). Prasugrel is being co-developed by
Daiichi Sankyo Company, Limited (TSE: 4568) and Eli Lilly and Company
"The TRITON data demonstrate the statistical superiority of this
new antiplatelet therapy to prevent heart attacks, and validate our
decision to test prasugrel head to head against clopidogrel," said J.
Anthony Ware, M.D., Lilly cardiovascular platform leader for
prasugrel. "We are very pleased with the trial's outcome and are
excited by the potential for these results to help us further tailor
prasugrel therapy to assure the greatest benefit from this novel
Cardiovascular disease is the leading cause of death in the U.S.
and worldwide, killing 16.7 million people each year(i). Acute heart
attacks and unstable angina, called acute coronary syndrome, affect
more than 840,000 Americans each year and 800,000 in Europe(i,ii).
Utilizing current medical interventions and treatments, 300,000
people continue to experience recurrent heart attacks and 450,000
people die from heart attacks annually in the U.S(iv).
"TRITON confirms the statistically superior clinical benefit of
prasugrel as a third-generation oral antiplatelet that may advance
cardiovascular care," said John Alexander, M.D., M.P.H., global head
of research and development, Daiichi Sankyo Company, Limited. "Given
the promising TRITON results, Daiichi Sankyo and Lilly are
expeditiously finalizing our submission package and are still hopeful
to submit to the FDA by year end."
About the TRITON TIMI-38 study
TRITON TIMI-38 was a Phase III, multi-center, randomized, double
blind, parallel group, head-to-head clinical trial comparing the
effects of prasugrel versus clopidogrel in patients with acute
coronary syndrome undergoing percutaneous coronary intervention
(PCI). PCI is a procedure to open blockages in heart arteries
including the use of coronary stenting. The study enrolled 13,608
patients at 707 trial sites in 30 countries.
The primary endpoint of the study was to compare the effects of
prasugrel to clopidogrel on the composite incidence of cardiovascular
death, non-fatal heart attack and non-fatal stroke during a median
period of at least 12 months following PCI. Key secondary objectives
included rehospitalization for a cardiac ischemic event; the need for
additional procedures to restore blood flow (urgent target vessel
revascularization) at 30 days; and stent thrombosis. Key safety
endpoints included non-CABG major, life threatening and minor
bleeding as well as the overall safety and tolerability of prasugrel.
Patients were randomly assigned to one of two treatment groups and
given a loading dose of either prasugrel 60 mg or the approved
loading dose of clopidogrel 300 mg anytime between randomization and
one hour after the completion of the PCI procedure, followed by a
daily maintenance dose of either prasugrel 10 mg or clopidogrel 75
mg. All patients also received a daily low dose of aspirin.
Antiplatelet agents are critical for both acute and maintenance
therapy to inhibit platelet activation and subsequent aggregation
that occur in diseased arteries and as adjunct therapy to invasive
procedures such as percutaneous coronary intervention.
Daiichi Sankyo Company, Limited (TSE: 4568), and Eli Lilly and
Company (NYSE: LLY) are co-developing prasugrel, an investigational
oral antiplatelet agent invented by Daiichi Sankyo and its Japanese
research partner Ube Industries, Ltd., as a potential treatment,
initially for patients with acute coronary syndrome undergoing PCI.
Prasugrel works by inhibiting platelet activation and subsequent
aggregation by blocking the P2Y12 adenosine diphosphate (ADP)
receptor on the platelet surface. Antiplatelet agents prevent
platelets from clumping or sticking together, which can result in
clogged arteries and may lead to heart attack or stroke.
About Daiichi Sankyo Company, Limited
Daiichi Sankyo Company, Limited, established in 2005 after the
merger of two leading century-old Japanese pharmaceutical companies,
is a global pharmaceutical innovator, continuously generating
innovative drugs that enrich the quality of life for patients around
the world. The company uses its cumulative knowledge and expertise in
the fields of cardiovascular disease, cancer, metabolic disorders,
and infection as a foundation for developing an abundant product
lineup and R&D pipeline.
About Eli Lilly and Company
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.
This press release contains certain forward-looking statements
about the potential of the investigational compound prasugrel
(CS-747, LY640315) and reflects Daiichi Sankyo's and Lilly's current
beliefs. However, as with any pharmaceutical compound under
development, there are substantial risks and uncertainties in the
process of development and regulatory review. There is no guarantee
that the compound will receive regulatory approval, that the
regulatory approval will be for the indication(s) anticipated by the
companies, or that later studies and patient experience will be
consistent with study findings to date. There is also no guarantee
that the compound 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 and Daiichi Sankyo's filings with the Tokyo Stock
Exchange. Daiichi Sankyo and Lilly undertake no duty to update
Plavix(R)/Iscover(R) are registered trademarks of
(i) World Health Organization. The Atlas of Heart Disease and
Stroke - Types of Cardiovascular Disease 2005.
(ii) American Heart Association. Heart Disease and Stroke
Statistics - 2006 Update. Dallas, TX. American Heart Association.
(iii) Bertrand CURE study
(iv) American Heart Association. Heart Attack and Angina
accessed July 26, 2007.
(Logo: http://www.newscom.com/cgi-bin/prnh/20070601/CLF003LOGO )
ots Originaltext: Eli Lilly and Company
Im Internet recherchierbar: http://www.presseportal.ch
Joedy Isert, Eli Lilly and Company, +1-317-276-5592, +1-317-997-8544
(cell); Jo-ann Straat, Daiichi Sankyo (USA), +1-973-359-2602,
Shigemichi Kondo, Daiichi Sankyo (Tokyo), +81-3-6225-1126; Photo:
NewsCom: http://www.newscom.com/cgi-bin/prnh/20070601/CLF003LOGO, AP
Archive: http://photoarchive.ap.org, PRN Photo Desk,