Lilly Announces New Data Further Exploring Mechanistic Differences
Between FORTEO® (teriparatide [rDNA origin] injection) and
Zoledronic Acid
INDIANAPOLIS, Oct. 15, 2012 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) today presented data comparing the effects of
FORTEO and zoledronic acid on transiliac crest bone biopsies at six
months in postmenopausal women with osteoporosis, based on
additional analysis of data from the SHOTZ trial. Results, which
were presented in an oral presentation at the 2012 Annual Meeting
of the American Society for Bone and Mineral Research (ASBMR) in
Minneapolis, MN, clearly
differentiate the mechanism of action of FORTEO as anabolic and
that of zoledronic acid as antiresorptive.
The data show that the contrasting effects of FORTEO and
zoledronic acid on bone remodeling are evident on all three bone
surfaces: cancellous, endocortical and periosteal. The
effects on mineralizing surface (MS/BS) and bone formation rate
(BFR/BS) – dynamic indices of bone formation and turnover –
provided clear differentiation of the mechanism of action of the
two drugs at six months.1
"This study continues to differentiate these two established
osteoporosis treatments with different mechanisms of action and
further contrasts the anticatabolic action of zoledronic acid and
the anabolic action of teriparatide on all three bone surfaces,"
said David W. Dempster, PhD,
professor of clinical pathology, Columbia
University. "It is important to understand the effect of
antifracture drugs on cortical bone, which makes up 80 percent of
the adult skeleton."
Previously, researchers used dynamic histomorphometry, a
technique to measure cellular activities of remodeling at the bone
tissue level, to explore the mechanisms of action of FORTEO and
zoledronic acid in the cancellous compartment of bone biopsies. In
this study, researchers extended their observations to the outer
and inner surfaces of cortical bone.
In a typical bone sample, the internal meshwork, or cancellous
bone, is surrounded with cortical bone. The cortical bone has two
surfaces; the endocortical (inner) surface is adjacent to
cancellous bone, and the periosteal (outer) surface forms the
external bone surface.
These study results showed that the contrasting effects of
FORTEO and zoledronic acid on bone remodeling were evident on all
three bone envelopes measured. The dynamic index of bone formation,
mineralizing surface (MS/BS), was a striking differentiator between
the drugs:
- cancellous (median: 5.6 percent [FORTEO] vs. 0.16 percent
[zoledronic acid]);
- endocortical (median: 18.64 percent [FORTEO] vs. 0.30 percent
[zoledronic acid]); and
- periosteal (median: 0.71 percent [FORTEO] vs. 0.0 percent
[zoledronic acid]).
Similar results were observed for other histomorphometric
indices such as bone formation rate (BFR), mineral apposition rate
(MAR), osteoid surface (OS/BS), osteoid thickness (O.Th) and wall
thickness (W.Th); all of which were significantly higher in the
FORTEO than the zoledronic acid group in both cancellous and
endocortical envelopes. Conversely, in both envelopes, eroded
surface (ES/BS) was lower in the zoledronic acid than the
teriparatide group. Periosteal MS/BS and BFR/BS were greater with
FORTEO than with zoledronic acid treatment.1
Although the effect of FORTEO was smaller on the periosteal
surface than the endocortical surface, the greater values for
dynamic indices relative to the zoledronic acid group suggests the
possibility of periosteal expansion, and possibly an increase in
bone size with FORTEO treatment. Further, in FORTEO samples, MS/BS
and BRF/BS were higher in the endocortical than the cancellous
envelope which, coupled with an increase in wall thickness,
provides a mechanism for cortical thickening with FORTEO
treatment.1
In the study, the overall safety profile was consistent with the
known FORTEO safety profile seen in this patient population. The
overall incidence of serious adverse events, treatment-emergent
adverse events and adverse events leading to discontinuation were
similar between the FORTEO and zoledronic acid treatment
groups.1
"We believe these data help further explain the growing body of
evidence supporting the mechanism of action of FORTEO," said
Anthony Beardsworth, M.D., senior
medical director, Eli Lilly and Company. "The results may help
healthcare professionals better determine osteoporosis treatment
for their individual patients."
FORTEO is used in both men and postmenopausal women with
osteoporosis who are at high risk for having broken bones
(fractures). FORTEO is used in both men and women with osteoporosis
due to use of glucocorticoid medicines, such as prednisone, for
several months, who are at high risk for having broken bones
(fractures). FORTEO can be used by people who have had a fracture
related to osteoporosis, or who have several risk factors for
fracture, or who cannot use other osteoporosis
treatments.2
During the drug testing process, the medicine in FORTEO caused
some rats to develop osteosarcoma, which, in humans, is a serious
but rare bone cancer. Osteosarcoma has been reported rarely in
people who took FORTEO®, and it is unknown if people who
take FORTEO have a higher chance of getting the disease. Before
patients take FORTEO, patients should tell their healthcare
provider if they have Paget's disease of bone, are a child or young
adult whose bones are still growing or have had radiation
therapy.2 For more information about FORTEO, please see
the important safety information, including Boxed Warning regarding
osteosarcoma, below.
About the Study1
Results from this study were taken from the SHOTZ
(Skeletal Histomorphometry in Patients On
Teriparatide or Zoledronic Acid Therapy) Trial. The
study was a 12-month, randomized, double-blind, active
comparator-controlled study that compared, at six months,
histomorphometric indices in the cancellous, endocortical and
periosteal bone envelopes from bone biopsies obtained from 58
postmenopausal women with osteoporosis at high risk for fracture.
Participants received either 20 mg/d teriparatide (TPTD, n=28) or 5
mg/y zoledronic acid (ZOL, n=30).
Participants aged 55 to 89 years were enrolled based on bone
mineral density (BMD) and fracture criteria as assessed by the
investigators.
Important Safety Information about FORTEO
What is the most important information I should know about
FORTEO?
WARNING: POTENTIAL RISK OF
OSTEOSARCOMA
|
During
the drug testing process, the medicine in FORTEO caused some rats
to develop a bone cancer called osteosarcoma. In people,
osteosarcoma is a serious but rare cancer. Osteosarcoma has been
reported rarely in people who took FORTEO. It is not known if
people who take FORTEO have a higher chance of getting
osteosarcoma. Before you take FORTEO, you should tell your
healthcare provider if you have Paget's disease of bone, are a
child or young adult whose bones are still growing, or have had
radiation therapy.
|
Who should not take FORTEO?
- You should not take FORTEO for more than 2 years over your
lifetime.
- Do not use FORTEO if you are allergic to any of the ingredients
in FORTEO. Serious allergic reactions have been reported.
What should I tell my healthcare provider before taking
FORTEO?
- Before you take FORTEO, you should tell your healthcare
provider if you have a bone disease other than osteoporosis, have
cancer in your bones, have trouble injecting yourself and do not
have someone who can help you, have or have had kidney stones, have
or have had too much calcium in your blood, take medications that
contain digoxin (Digoxin, Lanoxicaps, Lanoxin), or have any other
medical conditions.
- You should also tell your healthcare provider, before you take
FORTEO, if you are pregnant or thinking about becoming pregnant. It
is not known if FORTEO will harm your unborn baby. If you are
breastfeeding or plan to breastfeed, it is not known if FORTEO
passes into your breast milk. You and your healthcare provider
should decide if you will take FORTEO or breastfeed. You should not
do both.
What are the possible side effects of FORTEO?
- FORTEO can cause serious side effects including a decrease in
blood pressure when you change positions. Some people feel dizzy,
get a fast heartbeat, or feel faint right after the first few
doses. This usually happens within 4 hours of taking FORTEO and
goes away within a few hours. For the first few doses, take your
injections of FORTEO in a place where you can sit or lie down right
away if you get these symptoms. If your symptoms get worse or do
not go away, stop taking FORTEO and call your healthcare provider.
FORTEO may also cause increased calcium in your blood. Tell your
healthcare provider if you have nausea, vomiting, constipation, low
energy, or muscle weakness. These may be signs there is too much
calcium in your blood.
- Common side effects of FORTEO include nausea, joint aches,
pain, leg cramps, and injection site reactions including injection
site pain, swelling and bruising. These are not all the
possible side effects of FORTEO. You are encouraged to report
negative side effects of Prescription drugs to the FDA. Visit
www.fda.gov/medwatch or call 1-800-FDA-1088.
Additional safety information about FORTEO
- There is a voluntary patient registry for people who take
FORTEO. The purpose of the registry is to collect information about
the possible risk of osteosarcoma in people who take FORTEO. For
information about how to sign up for this patient registry, call
1-866-382-6813 or go to www.forteoregistry.org.
- The FORTEO Delivery Device has enough medicine for 28 days. It
is set to give a 20-microgram dose of medicine each day. Before you
try to inject FORTEO yourself, a healthcare provider should teach
you how to use the FORTEO Delivery Device to give your injection
the right way. Inject FORTEO one time each day in your thigh or
abdomen (lower stomach area). Do not inject all the medicine in the
FORTEO Delivery Device at any one time. Do not transfer the
medicine from the FORTEO Delivery Device to a syringe. This can
result in taking the wrong dose of FORTEO. If you take more FORTEO
than prescribed, call your healthcare provider. If you take too
much FORTEO, you may have nausea, vomiting, weakness, or
dizziness.
How should I store FORTEO?
- Keep your FORTEO Delivery Device in the refrigerator between 36
degrees F to 46 degrees F (2 degrees C to 8 degrees C). Do not
freeze the FORTEO Delivery Device. Do not use FORTEO if it has been
frozen. Do not use FORTEO after the expiration date printed on the
delivery device and packaging. Throw away the FORTEO Delivery
Device after 28 days even if it has medicine in it (see the User
Manual).
For more safety information, please see Medication Guide
(http://pi.lilly.com/us/forteo-medguide.pdf) and Prescribing
Information (http://pi.lilly.com/us/forteo-pi.pdf), including Boxed
Warning regarding osteosarcoma. Please see full user manual
that accompanies the delivery device.
TE Con ISI 07Mar2011
About Eli Lilly and Company
Eli Lilly and Company, a leading innovation-driven company, is
developing a growing portfolio of 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.
Information about Lilly is available at www.lilly.com.
P-LLY
FORTEO® is a registered trademark of Eli Lilly
and Company.
This press release contains forward-looking statements about
Forteo for the treatment of osteoporosis. It reflects Lilly's
current beliefs; however, as with any such undertaking, there are
substantial risks and uncertainties in the process of drug
development and commercialization. There is no guarantee that
future study results and patient experience will be consistent with
study findings to date or that Forteo will continue to be
commercially successful. For further discussion of these and other
risks and uncertainties, please see Lilly's latest Forms 10-Q and
10-K filed with the U.S. Securities and Exchange Commission. Lilly
undertakes no duty to update forward-looking statements.
1 Dempster, D., et al. "Differential Effects of
Teriparatide and Zoledronic Acid on the Outer and Inner Surfaces of
Cortical Bone in Postmenopausal Women with Osteoporosis: Results
from the SHOTZ Trial." Abstract presented at the ASBMR 2012 Annual
Meeting, Oct.15, 2012, 10:15 AM.
2 FORTEO PI. Available at
http://pi.lilly.com/us/forteo-pi.pdf.
(Logo: http://photos.prnewswire.com/prnh/20031219/LLYLOGO
)
SOURCE Eli Lilly and Company