SAN DIEGO, Sept. 19, 2011 /PRNewswire/ -- Eli Lilly and Company LLY today presented data comparing the mechanisms of action of FORTEO® (teriparatide [rDNA origin] injection) and zoledronic acid based on data that evaluated histomorphometric measurements of bone remodeling in transiliac crest bone biopsies from postmenopausal women with osteoporosis. These data were presented in an oral presentation at the 2011 Annual Meeting of the American Society for Bone and Mineral Research (ASBMR) in San Diego, Calif.

Dynamic indices of bone formation, including mineralizing surface/bone surface (MS/BS) and bone formation rate (BFR), were significantly higher in women treated with FORTEO than in women treated with zoledronic acid at six months.¹

“What makes this study important is that it was through the use of a complete panel of bone biopsy indices that we confirmed the differences in the mechanism of action of the two osteoporosis treatments,” said David W. Dempster, PhD, professor of clinical pathology, Columbia University.

The study's primary objective was to compare the effects of FORTEO or zoledronic acid on MS/BS at six months. MS/BS is a measure of the proportion of bone surface upon which newly mineralized bone is being deposited.² Results showed that in women treated with FORTEO, MS/BS was significantly higher than in those treated with zoledronic acid (median: 5.60 percent vs. 0.16 percent; p<0.001).  

Secondary outcomes demonstrated:

• a significantly greater increase in BFR/BS (bone formation rate/bone surface) in patients taking FORTEO (median: 0.0116 mm³/mm²/y) compared to those taking zoledronic acid (median: 0.0009 mm³/mm²/y) (p<0.001) (double-labels only);¹
• a significantly greater increase in mineral apposition rate (MAR) in patients taking FORTEO (median: 0.56 μm/d) compared to those taking zoledronic acid (median: 0.50 μm/d) (p=0.03) (double-labels only);¹
• increased serum markers of bone formation and resorption (P1NP, OC and CTX) with FORTEO; zoledronic acid decreased these markers; ³ and
• adverse event profiles for both drugs that were similar to those reported previously and contained within the product labeling.

“We believe that these data make an important contribution to the body of evidence supporting the mechanism of action for FORTEO,” said Kathleen Taylor, PhD, Eli Lilly and Company.

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.⁴

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.⁴ For more information about FORTEO, please see the important safety information, including Boxed Warning regarding osteosarcoma, below.

About the Study⁵

“Skeletal Histomorphometry in Patients On Teriparatide or Zoledronic Acid Therapy (SHOTZ) Study: 6-Month Results of a Randomized Clinical Trial” was a six-month, randomized, double-blind, cross-sectional biopsy study that compared histomorphometric parameters of bone remodeling in 58 postmenopausal women with osteoporosis. Participants received either 20 μg/d teriparatide (TPTD, n=28) or 5 mg/y zoledronic acid (ZOL, n=30).

The study's primary endpoint was the comparison of mineralizing surface/bone surface (MS/BS) between treatment groups, assessed by bone histomorphometry in cancellous compartment of iliac crest bone biopsy at month six (obtained after double tetracycline labeling). Secondary endpoints included comparison of bone formation rate (BFR/BS), mineral apposition rate (MAR) and other standard histomorphometric indices in iliac crest bone biopsies at six months; change from baseline to months one, three and six in biochemical markers of bone turnover; and safety evaluations of vital signs, laboratory analyses, pre-biopsy assessments and treatment-related adverse events.

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?

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°F to 46°F (2°C to 8°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, including Boxed Warning (http://pi.lilly.com/us/forteo-pi.pdf).  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.

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¹ Dempster, D., et al. “Skeletal Histomorphometry in Patients On Teriparatide or Zoledronic Acid Therapy (SHOTZ) Study: 6–Month Results of a Randomized Clinical Trial.” Abstract presented at the ASBMR 2011 Annual Meeting, Sept. 19, 2011, 3:45 PM. <Page 3, Table 1.>

² Moreira Kulak CA, Dempster DW. Bone histomorphometry: a concise review for endocrinologists and clinicians. Arq Bras Endocrinol Metab. 2010;54(2):87-98.

³ Dempster, D., et al. “Skeletal Histomorphometry in Patients On Teriparatide or Zoledronic Acid Therapy (SHOTZ) Study: 6–Month Results of a Randomized Clinical Trial.” Abstract presented at the ASBMR 2011 Annual Meeting, Sept. 19, 2011, 3:45 PM. <Page 1, Paragraph 2 “Results.”>

⁴ FORTEO PI. Available at http://pi.lilly.com/us/forteo-pi.pdf.

⁵ Dempster, D., et al. “Skeletal Histomorphometry in Patients On Teriparatide or Zoledronic Acid Therapy (SHOTZ) Study: 6–Month Results of a Randomized Clinical Trial.” Abstract presented at the ASBMR 2011 Annual Meeting, Sept. 19, 2011, 3:45 PM. <Page 1, Paragraph 1 “Purpose.”>

SOURCE Eli Lilly and Company