New Analysis Showed Early Patient Response to FORTEO(R) in Postmenopausal Women with Osteoporosis
June 16 2004 - 8:00AM
PR Newswire (US)
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. (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Keri McGrath of Eli Lilly and
Company, +1-317-457-5613, , or Pager: +1-877-517-0663
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