FORTEO(R) Increased Spine Bone Mineral Density in Patients with Glucocorticoid-Induced Osteoporosis
November 14 2007 - 4:00PM
PR Newswire (US)
Multi-national study compared FORTEO and the currently approved
therapy Fosamax for the treatment of Glucocorticoid-Induced
Osteoporosis INDIANAPOLIS, Nov. 14 /PRNewswire-FirstCall/ -- New
data, published today in The New England Journal of Medicine,
showed that in patients with glucocorticoid-induced osteoporosis
FORTEO(R) (PTH 1-34, teriparatide [rDNA origin] injection)
significantly increased lumbar spine bone mineral density (BMD)
from baseline (8.2 percent) compared to Fosamax(R) (alendronate,
3.9 percent) at 18 months of therapy.(1) In this head-to-head
comparator study, the increase in lumbar spine BMD was
significantly greater in patients receiving teriparatide compared
with alendronate at 6, 12, and 18 months of treatment (p < 0.001
at all time points).(1) Glucocorticoid therapy is the most common
cause of secondary osteoporosis,(2) leading to bone loss and an
increased risk for fracture. Data indicate that glucocorticoids are
used by up to three out of every 100 adults (3 percent) over age
50,(3) and up to 50 percent of individuals on chronic
glucocorticoid therapy will eventually have an osteoporotic
fracture.(4) Glucocorticoids are prescribed to treat many
conditions, including rheumatoid arthritis, chronic obstructive
pulmonary disease and inflammatory bowel disease.(4,5) "Currently,
there is a lack of variety in treatment choices for patients
receiving chronic glucocorticoid medication who are at high risk
for fractures," said lead investigator Kenneth G. Saag, M.D., MSc,
professor of medicine and epidemiology at the University of Alabama
in Birmingham. "These data are important because they show that
teriparatide may have the potential to be a viable therapeutic
option in the future for people with this disease." Teriparatide is
not indicated for the treatment of glucocorticoid-induced
osteoporosis. Teriparatide is the first osteoporosis therapy
approved by the U.S. Food and Drug Administration (FDA) and the
European Medicines Agency (EMEA) that rebuilds bone in
postmenopausal women with osteoporosis who are at high risk for
fracture and increases bone mass in men with primary or hypogonadal
osteoporosis who are at high risk for fracture.(5,6) Teriparatide
is marketed as FORSTEO in the European Union. In February and June
2007, Lilly filed applications with the FDA and EMEA, respectively,
for a supplemental indication for teriparatide for the treatment of
men and women with osteoporosis associated with glucocorticoid
therapy and who are at high risk for fracture. These patients
either have a history of osteoporotic fracture or low bone mineral
density.(7) About the Study In a double-blind, active
comparator-controlled trial, 428 patients with
glucocorticoid-induced osteoporosis were randomized to receive
once-daily subcutaneous injections of teriparatide (20 micrograms)
plus oral placebo or daily placebo injections plus once-daily oral
alendronate (10 mg). The study's primary endpoint was to determine
whether the increase in lumbar spine bone mineral density from
baseline to 18 months in patients receiving teriparatide was
greater than in patients receiving alendronate.(1) Data published
in the current issue of The New England Journal of Medicine
represent the 18-month primary phase results of this 36-month
trial. The 18- month continuation phase is ongoing. The study
included men and women aged greater than or equal to 21 years on
sustained glucocorticoid therapy (prednisone equivalent of greater
than or equal to 5 mg/day for greater than or equal to 3 months).
Patient's spine or hip T-scores were either -2.0 or less, or -1.0
or less with one or more fractures.(1) Efficacy data after
18-months of therapy:(1) -- The mean increase in lumbar spine BMD
with teriparatide was significantly greater compared with Fosamax
after six months through 18 months of therapy -- 8.2 plus or minus
0.6 percent increase with teriparatide and 3.9 plus or minus 0.6
percent increase with alendronate at 18 months (P < 0.001) --
The mean increase in total hip BMD with teriparatide was
significantly greater compared with alendronate after 12 months
(first measurement at the hip) through 18 months of therapy -- 3.8
plus or minus 0.6 percent increase with teriparatide and 2.4 plus
or minus 0.6 percent increase with alendronate at 18 months (P <
0.01) -- A preliminary analysis of new radiographic vertebral
fractures in patients with baseline and 18 month radiographs showed
that one patient receiving teriparatide (0.6 percent; 1 out of 171
patients) and 10 patients receiving alendronate (6.1 percent; 10
out of 165 patients) had greater than or equal to 1 new vertebral
fracture -- A preliminary analysis of nonvertebral fracture showed
that 12 patients receiving teriparatide (5.6 percent; 12 out of 214
patients) and eight patients receiving alendronate (3.7 percent; 8
out of 214 patients) had greater than or equal to 1 new
nonvertebral fracture There was no significant difference overall
in the number of patients reporting adverse events in patients
receiving teriparatide compared with alendronate.(1) Significant
differences between groups in individual adverse events included
nausea, insomnia, pharyngitis, and viral infection reported by more
patients receiving teriparatide than alendronate, and rash, weight
decrease, sciatica, and asthma reported by more patients receiving
alendronate than teriparatide.(1) A significantly higher proportion
of teriparatide than alendronate patients had at least one
post-baseline calcium in the hypercalcemia range (18.0 percent [38
out of 211 patients] for teriparatide and 5.7 percent [12 out of
207 patients] for alendronate (P < 0.001).(1) To view the
published manuscript, please visit http://www.nejm.org/.
Information about FORTEO(R) As part of drug testing, teriparatide,
the active ingredient in FORTEO(R), was given to rats for a
significant part of their lifetime. In these studies, teriparatide
caused some rats to develop osteosarcoma, a bone cancer.
Osteosarcoma in humans is a serious but very rare cancer.
Osteosarcoma occurs in about four out of every million older adults
each year. It is not known if humans treated with FORTEO also have
a higher chance of getting osteosarcoma. 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 external beam or implant
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 "boxed warning" in
its package insert about the osteosarcoma findings in rats during
preclinical testing. For full prescribing information, please visit
http://www.forteo.com/. 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 information about Lilly is
available at http://www.lilly.com/. P-LLY Forward Looking Statement
This press release contains forward-looking statements about the
safety and efficacy of FORTEO 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 FORTEO will continue
to be 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) N Engl J Med. 2007; TBD
(2) 2 Trends in Endo. And Meta. 2006;17(4); 144-149. (3) Clin
Rheumatol. 2007; 26: 144-153. (4) Endocrinol Metab Clin N Am. 2003;
32; 135-157. (5) N Engl J Med. 2001; 344: 1434-1441. (6)
Prescribing information for FORTEO. (7) Draft prescribing
information for FORTEO. (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: Sharon Corbitt of Eli Lilly and
Company, +1-317-277-1574, Mobile: +1-317-997-1206,
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