Eli Lilly and Company announced today that results of a
phase III clinical trial show drotrecogin alfa --proposed
brand name, zovant--reduced the relative risk of death from sepsis
with associated acute organ dysfunction (known as severe sepsis) by
19.4 percent. The new data, published today on The New England Journal
of Medicine's website (www.nejm.org), are from the PROWESS
(Recombinant Human Activated Protein C Worldwide Evaluation in Severe
Sepsis is a syndrome characterized by an overwhelming systemic
response to infection, which can rapidly lead to organ dysfunction and
ultimately death. Sepsis may cause multiple organs in the body to fail
and may trigger the onset of both abnormal clotting and bleeding.
Every day, sepsis results in the death of more than 1,400 people
worldwide and is the leading cause of death in noncoronary intensive
care units. The Estimated Costs Associated With The Treatment Of
Patients With Sepsis Are $17 Billion Annually In The United States.(1)
Currently, There Is No Drug Therapy Approved Specifically For The
Treatment Of Severe Sepsis.
"The data suggest that one in five people who would have died from
severe sepsis survived due to Zovant. We are extremely encouraged by
Zovant's potential to help so many who might otherwise succumb to the
ravages of sepsis," said August M. Watanabe, M.D., executive vice
president, science and technology, for Lilly. "The data give us hope
that this truly innovative biotech product, if approved, may help a
wide variety of sepsis patients."
Zovant is a recombinant version of naturally occurring activated
protein C, and study data indicate it may help balance many of the
major forces behind sepsis, including inflammation and clotting in the
blood vessels. In June 2000, enrollment in the PROWESS trial was
stopped early at the recommendation of an independent Data and Safety
Monitoring Board when an interim analysis indicated that the
placebo-controlled trial results met the prespecified criteria for
reduced mortality among patients treated with Zovant versus those
treated with placebo.
The results of PROWESS will also be presented on Feb. 11 at the
Society of Critical Care Medicine's 30th International Educational and
Scientific Symposium in San Francisco.
"Sepsis strikes hard and takes lives quickly -- three of ten
people in the trial died within only a month using the current
standard of care. It's exciting to think that Zovant may improve the
chances of survival from a syndrome that is so deadly," stated lead
clinical investigator for the trial Gordon Bernard, M.D., associate
director of the Division of Allergy, Pulmonary and Critical Care
Medicine, Vanderbilt University Medical Center. "After more than 20
investigational compounds studied over the years have failed to
produce a specific treatment for sepsis, the Zovant trial results are
a real breakthrough."
PROWESS Study Results
PROWESS was a perspective, double-blind, placebo-controlled trial
investigating the use of Zovant in patients who had sepsis with at
least one associated organ dysfunction. The trial included 1,690
patients from 11 countries who were randomized to receive either
placebo (n=840) or Zovant (n=850). The primary endpoint of the study
was 28-day all-cause mortality.
Trial data analysis showed a highly statistically significant
reduction in the relative risk of mortality of 19.4 percent
(p-value = 0.005) for those treated with Zovant, which was
administered as a continuous infusion of 24 micrograms per kilogram
per hour for 96 hours compared with those patients receiving placebo.
The mortality rates were 24.7 percent among Zovant-treated patients
versus 30.8 percent among patients treated with placebo. The response
to Zovant was consistent across almost all patient subgroups in the
clinical trial. Zovant increased the odds of survival by 38.1 percent.
The absolute risk reduction in mortality associated with Zovant
was observed within days of treatment and continued to increase
throughout the remainder of the study period.
Patients enrolled in the trial had a mean age of 60.5 years old.
Approximately 75 percent of the patients had two or more acute organ
dysfunctions associated with their sepsis. The primary sites of the
infection were the lung (53.6 percent) and abdomen (19.9 percent).
According to The New England Journal of Medicine article about the
study, Zovant had an impact regardless of whether patients were
protein C deficient. The data suggest that Zovant has pharmacologic
effects that go beyond simply replacing a body's activated protein C
and that protein C measurements are not needed to determine if a
patient would benefit from Zovant.
In the PROWESS study, the administration of Zovant was not
associated with an increased rate of drug-related complications other
than bleeding. Serious bleeding events were the most common serious
adverse event associated with Zovant therapy (3.5 percent for
Zovant-treated patients verses 2 percent in placebo-treated patients),
but the difference did not reach statistical significance. Serious
bleeding events occurred in both treatment groups mainly among a small
percentage of patients predisposed to bleeding.
Lilly applied for regulatory approval of Zovant in the United
States, European Union and Australia.
Eli Lilly and Company, a leading innovation-driven corporation, is
developing a growing portfolio of 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., Eli Lilly and
Company provides answers -- through medicines and information -- for
some of the world's most urgent medical needs.
This news release contains forward-looking statements that reflect
management's current beliefs about the potential for Zovant in the
treatment of severe sepsis. However, as with any pharmaceutical under
development, there are significant risks and uncertainties in the
process of development and regulatory review. There are no guarantees
that future clinical trials will confirm the results reported in this
release or that the product will receive regulatory approvals or prove
to be commercially successful. For further discussion of these and
other risks and uncertainties, see the company's most recent Form 10-Q
filing dated November 2000.
(1.) Calculated on data from Linde-Zwirble. Age-specific incidence
and outcome of sepsis in the U.S. Critical Care Medicine.
1999;27:1-9 (supplement, p A33).