New Analysis Showed Early Patient Response to FORTEO(R) in Postmenopausal Women with Osteoporosis

New Analysis Showed Early Patient Response to FORTEO(R) in
Postmenopausal Women with Osteoporosis
-- Changes in bone markers at one month may provide important information about
FORTEO's early benefits -- 


NEW ORLEANS, June 16  /PRNewswire-FirstCall/ -- Changes in markers of bone
remodeling after one month of treatment with FORTEO(R) (teriparatide [rDNA
origin] injection) may provide important early evidence of treatment response,
according to new data presented today at the 86th Annual Meeting of The
Endocrine Society (ENDO).

The Fracture Prevention Trial, (FPT), a registration trial for FORTEO, was a
randomized, double-blinded, placebo controlled study that enrolled 1,637 women
with osteoporosis.  Subjects were randomized to FORTEO 20 mcg/day, (the
currently approved and marketed dose), FORTEO 40 mcg/day or placebo for a
median of 19 months.

The sub analysis of 527 patients from the F P T (previously published in New
England Journal of Medicine, May 2001) found that as early as one month into
treatment, changes in markers of bone remodeling, particularly serum
carboxy-terminal propeptide of type I collagen (PICP), provided important
predictive information of subsequent bone mineral density (BMD) increases in
response to FORTEO.  BMD is used to both diagnose osteoporosis and monitor
treatment effectiveness.  Unlike BMD measurements, markers of bone remodeling
are able to detect delicate changes in the bone early in the treatment cycle --
sometimes within weeks of beginning a treatment.

"These findings are significant because they provide physicians and patients
early evidence that treatment with FORTEO is working," said lead investigator
Dr. Angelo Licata, Endocrinologist with the Cleveland Clinic. "Providing
physicians and patients with this information early in their treatment is
crucial in that it may help promote compliance, a common roadblock in
osteoporosis treatment."

FORTEO, the first and only bone formation agent approved for the treatment of
osteoporosis, was granted FDA approval on November 26, 2002.  It stimulates new
bone formation by increasing the number and activity of bone forming cells
called osteoblasts.  FORTEO is approved for the treatment of osteoporosis in
postmenopausal women who are at high risk for fracture and to increase bone
mass in men with primary or hypogonadal osteoporosis who are at high risk for
fracture.  These include men (and postmenopausal women) with a history of
osteoporosis-related fracture, or who have multiple risk factors for fracture,
or who have failed or are intolerant to previous osteoporosis therapy, based
upon physician assessment.

Until FORTEO's approval, the only approved osteoporosis treatments were
antiresorptives, which work mainly to slow or stop bone loss by reducing the
number and action of bone-removing cells called osteoclasts.

Details

The objective of this sub analysis was to determine if changes in markers of
bone turnover could predict increases in BMD at the lumbar spine after 18
months of treatment with FORTEO.  During the study, two markers of bone
formation (serum bone-specific alkaline phosphatase [BSAP], PICP) and two
markers of bone resorption (urinary free deoxypyridinoline/creatinine ratio
[DPD], urinary N-terminal telopeptide/creatinine ratio [NTx]) were assessed, as
was lumbar spine BMD.

As was observed in the Fracture Prevention Trial, markers of formation, PICP
and BSAP, increased after one month of FORTEO treatment.  Levels of PICP for
FORTEO 20 mcg and 40 mcg declined after one month and returned to near baseline
levels by 12 months.  Markers of resorption -- NTx and DPD -- increased after
one month of treatment.  All of theses changes were statistically significant
from baseline and placebo.

In this analysis, Spearman's correlation coefficient, a formula used to
determine the strength of a link between two sets of data, was calculated
between bone turnover markers at baseline, one, three and six months and the
18-month lumbar spine BMD response.  Bone turnover status at baseline
correlated with subsequent BMD responses for all four markers of turnover.
Among all studied biochemical markers, increases in PICP demonstrated the most
significant link between increases in lumbar spine BMD and marker levels. These
values for PICP at three and six months were significant only for the 40 mcg
group compared to placebo.  Significant correlations with NTx were seen in
those treated with the 40 mcg dose at three and six months.  While all other
bone turnover markers had weaker associations, overall, the change in PICP at
one month was the best predictor of the 18-month lumbar spine BMD response with
FORTEO.

Important Safety Information about FORTEO

In two-year studies in rats, teriparatide caused an increase in the incidence
of osteosarcoma, a malignant bone tumor, which was dependent on dose and
duration of treatment.  Although no case of osteosarcoma has been reported in
the patients who received FORTEO in clinical trials, it is not known if humans
treated with FORTEO are at increased risk for this cancer.  FORTEO should be
prescribed only to patients for whom the potential benefits are considered to
outweigh the potential risk.  The drug should not be prescribed for patients at
increased baseline risk for osteosarcoma, including patients with Paget's
disease of bone or unexplained elevations of alkaline phosphatase, children or
growing adults, or those who have had prior radiation therapy involving the
skeleton.  Additionally, patients with bone metastases or a history of skeletal
malignancies, and those with metabolic bone diseases other than osteoporosis,
should not receive FORTEO.  Patients with high levels of calcium in their blood
should not receive FORTEO due to the possibility of increasing their blood
levels of calcium.

In clinical trials, the most frequent treatment-related adverse events reported
at the 20-microgram (mcg) dose approved for marketing were mild, similar to
placebo and generally did not require discontinuation of therapy. Reported
adverse events that appeared to be increased by FORTEO treatment were leg
cramps and dizziness (2.6 and 8 percent, respectively), compared with placebo
(1.3 percent and 5.4 percent, respectively).

FORTEO is supplied in a disposable pen device that can be used for up to 28
days to give once-daily self-administered injections.  FORTEO is available in a
20-mcg dose and should be taken for a period of up to 24 months.  Lilly has
implemented a risk management program that includes comprehensive measures
regarding the appropriate use of FORTEO in the target patient population.  A
Medication Guide explaining the details of the drug to the patient also
accompanies the product.  FORTEO also has a black box warning in its package
insert about the osteosarcoma findings in rats during preclinical testing.

About Osteoporosis

More than 50 percent of all women over the age of 75 are estimated to have
osteoporosis, and due to their advanced age, have a high risk of fracture.  In
fact, most American women over the age of 50 will experience one or more
osteoporosis-related fractures during their lifetimes, and women with
osteoporosis who have two or more previous fractures have up to a nine times
greater risk of future fracture compared with women who have not suffered a
previous fracture.

About Lilly

Lilly, 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., Lilly
provides answers -- through medicines and information -- for some of the
world's most urgent medical needs.  Additional information about Lilly is
available at http://www.lilly.com/ .

For full prescribing information for FORTEO call 1-800-423-2313.

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DATASOURCE: Eli Lilly and Company



CONTACT:  Keri McGrath of Eli Lilly and Company, [phone],

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