Newly Published Phase III Study Shows Arzoxifene Significantly Increased Bone
Mineral Density
INDIANAPOLIS, Apr. 9 /PRNewswire-AsiaNet/ --
Phase III data, published online this week in the Journal of Clinical
Endocrinology & Metabolism, showed that arzoxifene, an investigational
selective estrogen receptor modulator (SERM) being developed by Eli Lilly and
Company (NYSE: LLY), significantly increased lumbar spine and total hip bone
mineral density (BMD) in postmenopausal women with normal or low bone mass,
versus placebo.
In addition, arzoxifene, dosed at 20 mg/day, decreased biochemical
markers of bone turnover, and showed a neutral effect on the uterus and
endometrium.
"It is encouraging that arzoxifene showed the potential of bone loss
prevention, with significant gains in BMD in the spine and hip areas in
postmenopausal women in this study," said lead investigator Michael
Bolognese, M.D., Bethesda Health Research Center in Bethesda, Maryland. "I am
pleased with the results from this study and believe that arzoxifene at 20
mg/day may be a therapeutic option worthy of continued development."
Arzoxifene is being studied for the prevention and treatment of
osteoporosis in postmenopausal women and the reduction of risk of invasive
breast cancer in postmenopausal women with osteoporosis or low bone mass.
These data are from the "FOUNDATION" Study, one of three Phase III trials
for arzoxifene. In March, data from the second Phase III trial called "NEXT"
study were presented at the European Society for Clinical and Economic
Aspects of Osteoporosis and Osteoarthritis (ECCEO) annual meeting. The third
Phase III trial, the "GENERATIONS" Study, is a five-year, randomized,
double-blind, placebo-controlled study assessing the effects of arzoxifene on
vertebral fracture incidence and on invasive breast cancer incidence in
postmenopausal women with osteoporosis or with low bone density. Results from
that trial are anticipated in late 2009.
About the "FOUNDATION" study
Effects of Arzoxifene on Bone Mineral Density and Endometrium in
Postmenopausal Women with Normal or Low Bone Mass
In this Phase III, double-blind, two-year, multi-center trial, 331
postmenopausal women with normal or low bone mass were randomized to receive
arzoxifene 20 mg/day or placebo. All subjects received elemental calcium 500
mg/day. The study's primary endpoints were change in lumbar spine and total
hip BMD, and endometrial safety measured by endometrial histology.
The study included women who were at least two years postmenopausal and
between the ages of 45 and 60 with an intact uterus. Subjects' femoral neck
or lumbar spine T-scores were between 0 and -2.5, and they did not have
pre-existing spine fractures.
24-month results included:(1)
- Arzoxifene significantly increased the lumbar spine BMD by 2.9% vs
placebo (arzoxifene, 1.6%; placebo, -1.3%, p<0.001); and total hip BMD by
2.2% vs placebo (arzoxifene 1.1%; placebo, -1.1%, p<1.001).
- Arzoxifene significantly decreased biochemical marker of bone
resorption C-terminal cross-linking telopeptide of type I collagen (CTX,
arzoxifene -30.01 percent, placebo 3.79 percent; p<0.001); and
biochemical marker of bone formation serum N-terminal propeptide of type
I collagen PINP, arzoxifene -38.81 percent, placebo -10.27 percent;
p<0.001).
- There was no significant difference overall in the number of subjects
reporting adverse events in the arzoxifene group compared with the placebo
group, with the exception of vaginal yeast infection (arzoxifene 4%,
placebo 0%, p=0.02).
- New or worsening hot flushes were not significantly different between
the arzoxifene and placebo groups (arzoxifene 12%, placebo 11%, p=0.87).
- There were no significant differences in the incidence of endometrial
hyperplasia or cancer between the arzoxifene and placebo groups, as
assessed by serial endometrial biopsy (arzoxifene 0, placebo 2) or in
endometrial thickness, as assessed by transvaginal ultrasound.
- There were no deaths or venous thromboembolic events.
"We are pleased with the outcomes of this study," said Adrien Sipos,
M.D., Ph.D., medical director for Eli Lilly and Company. "As a company, we
are committed to research that will help us offer patients new treatment
options and further advance understanding of how to best prevent and treat
osteoporosis, a disease which negatively impacts more than 200 million people
worldwide."(2)
Osteoporosis is a disease in which bones become fragile and more likely
to break. Primary osteoporosis, which is deterioration of bone mass that is
unassociated with other chronic illness, is related to aging and decreased
ovarian function, including menopause. If not prevented, or if left
untreated, osteoporosis can progress painlessly until a bone breaks.
According to the International Osteoporosis Foundation, 30 to 50 percent of
women will suffer a fracture related to osteoporosis in their lifetime.(3)
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. Additional
P-LLY
Forward Looking Statement
This press release contains forward-looking statements about the safety
and efficacy of arzoxifene and reflects Lilly's current beliefs. However, as
with any pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization. There is
no guarantee that arzoxifene will become commercially successful. For further
discussion of these and other risks and uncertainties, see Lilly's filings
with the United States Securities and Exchange Commission. Lilly undertakes
no duty to update forward-looking statements.
(1) Journal of Clinical Endocrinology and Metabolism Web site.
April 7, 2009.
(2) Cooper C. Epidemiology of Osteoporosis. Osteoporosis Intl
1999;9 (Suppl2): S2-8.
(3) International Osteoporosis Foundation. Facts and Statistics About
Osteoporosis and its Impact. Available at:
-17. Accessed January 26, 2009.
SOURCE: Eli Lilly and Company
CONTACT: Teresa Shewman,
Eli Lilly and Company,
Office: +1-317-433-1888,
Mobile: +1-317-292-8940,
Shewman_Teresa@lilly.com
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