(This article was originally published Sunday.)
By Peter Loftus
The blood thinner Effient wasn't significantly better than the
widely used anti-clotting drug Plavix at preventing heart attacks
and strokes in a clinical trial of cardiovascular patients.
The study's outcome was a setback in efforts by Effient's
co-marketers, Eli Lilly & Co. (LLY) and Daiichi Sankyo Co.
(4568.TO), to expand the patient population for the drug, whose
uptake has been relatively limited because it carries a serious
bleeding risk.
"For the medically managed patients, I would say our trial does
not change what physicians are currently doing," said Magnus Ohman,
a cardiologist at Duke University and one of the principal
investigators of the study.
The study results are slated to be presented Sunday at the
European Society of Cardiology's annual scientific meeting in
Munich and published online by the New England Journal of
Medicine.
Adding to the challenge for Effient: low-cost generic versions
of Plavix recently went on sale in the U.S., making the
higher-priced, branded Effient a tougher sell in the absence of
more compelling clinical trial results.
Branded Plavix, which is co-marketed by Bristol-Myers Squibb Co.
(BMY) and Sanofi (SNY), lost U.S. patent protection in May,
triggering the availability of competing generics. Generic Plavix,
known as clopidogrel, costs $13.87 for a 30-day supply at Costco
pharmacies, versus $211.83 for Effient, according to Costco's
website.
Executives from Lilly and Daiichi said they were disappointed in
the study's outcome, but they didn't expect it to have a major
impact on use of Effient.
Lilly and Daiichi initially secured U.S. Food and Drug
Administration approval of Effient in 2009 based on a prior
clinical study showing the drug reduced the risk of heart attacks
and related events versus Plavix, in people with acute coronary
syndrome, or ACS, who are undergoing certain procedures including
inserting artery-opening stent devices. ACS includes angina, or
chest pain, and certain types of heart attacks.
However, that study also showed Effient increased the risk of
major bleeding versus Plavix. As a result, Effient's prescribing
label carries a prominent, black-boxed warning that the drug can
cause significant bleeding, and that it's generally not recommended
for people age 75 and older because of limited benefit and bleeding
risk in that group.
The bleeding risk has limited Effient's commercial success.
Lilly recorded $302.5 million in Effient sales for 2011.
Like Plavix, Effient is an antiplatelet drug designed to prevent
formation of blood clots implicated in heart attacks and
strokes.
To potentially broaden Effient's use, Lilly and Daiichi started
another study in 2008 to compare Effient and Plavix in medically
managed patients with ACS who did not undergo procedures known as
revascularizations. These include stent-insertion procedures as
well as heart-bypass surgeries.
Plavix is currently approved for use in medically managed ACS
patients, in addition to those undergoing stent and other
procedures.
The targeted enrollment was about 10,000 patients, who received
Effient plus aspirin or Plavix plus aspirin daily for up to 30
months. As the study's primary measure, researchers tracked the
combined incidence of cardiovascular deaths, heart attacks and
strokes in each therapy group.
Among patients under the age of 75--who accounted for about
three-fourths of the study population--one or more of these events
occurred in 13.9% of Effient users at a median follow-up of 17
months, versus 16% in the Plavix group. While that may appear to
suggest a modest benefit in favor of Effient, the difference wasn't
statistically significant. Similar results were observed in the
overall population, including the roughly one-fourth of patients
over the age of 75.
Rates of severe bleeding and bleeding inside the skull were
similar between the Effient and Plavix groups. Overall major or
minor bleeding among patients under 75 was higher in the Effient
users than among Plavix users, 1.9% versus 1.3%.
In contrast to the prior study, the Trilogy study excluded
patients with a prior history of stroke and it adjusted the Effient
dose for people 75 and older and those weighing less than 60
kilograms, which helped mitigate the risk. In the prior study,
Effient showed increased bleeding risk among people with history of
stroke, those over 75 and those under 60 kilograms.
Dr. Ohman said the relatively neutral bleeding effect in the
latest study could give doctors confidence in the long-term safety
of Effient.
Lilly and Daiichi saw other hints of benefit in the study
including a reduction in the risk of multiple recurrent
cardiovascular events associated with Effient versus Plavix.
But given the negative outcome on the primary goal, the
companies will focus on maximizing Effient's use in the patient
population for which it is currently approved: ACS patients
undergoing stent and related procedures. "We'll continue to explore
that and hope to convince more and more doctors to use the drug,"
said Glenn Gormley, global head of research and development for
Daiichi.
The companies also continue to study Effient in additional
trials, including one testing whether pretreating patients
scheduled for stent procedures improves outcomes, said Anthony
Ware, a group vice president for cardiovascular development at
Lilly.
Write to Peter Loftus at peter.loftus@dowjones.com
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