Mechanism of action: treatment with Forteo stimulates an increase in remodeling with positive bone balance2,3

FORTEO IS A PRO-REMODELING ANABOLIC AGENT2,3

  • Bone remodeling is a coupled process by which osteoclasts remove existing or damaged bone matrix (resorption), and then osteoblasts refill the resorption cavities with new bone (formation)4
  • This coupled process of continuous renewal helps to maintain mechanical strength of the skeleton4
  • In postmenopausal osteoporosis, increased bone turnover results in increased resorption, underfilling of resorption sites, and a deficit of bone with every cycle5
  • This can result in thinning of bone trabeculae, loss of connectivity, and a reduction in bone strength5
Normal Remodeling4
Neutral Bone Balance3
Dysregulated Remodeling5
Negative Bone Balance3
FORTEO increases bone remodeling2
Positive Bone Balance3
Osteoblast Osteoclast

TREATMENT WITH FORTEO STIMULATES AN INCREASE IN REMODELING WITH POSITIVE BONE BALANCE2,3

resulting in renewal of bone by: 2,3

  • removing older or fatigued bone
  • adding more bone than was present prior to treatment

FORTEO SELECT SAFETY INFORMATION


Prescribe FORTEO only for patients for whom the potential benefits are considered to outweigh the potential risks. FORTEO should not be prescribed for patients at increased baseline risk for osteosarcoma, including those with Paget's disease of bone, unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, or prior external beam or implant radiation therapy. Additionally, patients with bone metastases or a history of skeletal malignancies, metabolic bone diseases other than osteoporosis, or pre-existing hypercalcemia should not receive FORTEO.

FORTEO HELPED STIMULATE EARLY AND SUSTAINED BONE FORMATION IN 2 RANDOMIZED CLINICAL STUDIES

FORTEO helped stimulate new bone formation in cancellous and cortical bone as early as 3 months,* and sustained new bone formation throughout 24 months* of treatment 6,7

Ava Study

3 mo cancellous
3 mo cortical

Shotz Study

6 mo cancellous §
6 mo cortical

Shotz Study

24 mo cancellous
24 mo cortical #

Continuous and statistically significant bone formation demonstrated that anabolic action continued through 24 months of treatment with FORTEO.7

Please see study designs for AVA and SHOTZ studies

  • * 3-month data are from the AVA study, 6- and 24-month data are from the SHOTZ study.
  • ‡ Early evidence of bone formation in both cancellous and cortical bone envelopes.
  • § Bone formation (bridging) between 2 trabeculae; mechanistic evidence of increases in connectivity stimulated by FORTEO treatment.
  • ‖ Evidence of bone formation in all 3 cortical envelopes; note the convex packet of new bone on the endocortical surface.
  • ¶ The labels administered at 6 and 24 months can both be seen, allowing visualization of new bone formed in the intervening 18 months.
  • # The Haversian system that was in the formation phase of the cycle at 6 months is closed at month 24.

FORTEO SELECT SAFETY INFORMATION


The safety and efficacy of FORTEO have not been evaluated beyond 2 years of treatment. The use of FORTEO for more than 2 years during a patient's lifetime is, therefore, not recommended. Do not use FORTEO in patients with hypersensitivity to teriparatide or to any of its excipients. Reactions have included angioedema and anaphylaxis.

IN A CLINICAL STUDY

FORTEO HELPED STIMULATE NEW BONE WITH MINERAL PROPERTIES CONSISTENT WITH YOUNGER BONE AGE8

FORTEO treatment increased the amount of newly formed bone matrix with lower, more heterogeneous mineral content (blue arrows ), a property consistent with younger bone age.*

* Younger bone age is characterized by newly formed bone matrix with lower, more heterogeneous bone mineral content.

FORTEO SELECT SAFETY INFORMATION

FORTEO may increase serum calcium, urinary calcium, and serum uric acid. In clinical trials, neither sustained hypercalcemia nor hypercalciuria were observed.

Use with caution in patients with active or recent urolithiasis because of risk of exacerbation. If active urolithiasis or preexisting hypercalciuria are suspected, measurement of urinary calcium excretion should be considered. Patients receiving digoxin should use FORTEO with caution because FORTEO may transiently increase serum calcium and hypercalcemia may predispose patients to digitalis toxicity.

STUDY DESIGNS BELOW ARE FOR CLINICAL DATA PRESENTED ABOVE

AVA HISTOMORPHOMETRY STUDY6

*Data are from the AVA Study, a phase 4 randomized, active-comparator-controlled, bone biopsy study. Transiliac crest bone biopsies were obtained from ambulatory postmenopausal women with osteoporosis (age 55-89) at 3 months (n=31) after initiation of teriparatide treatment. At baseline and prior to the single 3-month biopsy, patients were labeled with demeclocycline and then tetracycline respectively in a 3:12:3:5 day schedule. Longitudinal changes were assessed in the cancellous, endocortical, intracortical and periosteal envelopes using a standard panel of histomorphometric indices. Representative images were taken with standard light microscopy and UV light illumination.

SHOTZ HISTOMORPHOMETRY STUDY7

†Data are from the SHOTZ study, a phase 4 randomized, active-comparator-controlled, bone biopsy study. Transiliac crest bone biopsies were obtained from ambulatory postmenopausal women with osteoporosis (age 55-89) at 6 months (n=28) or 24 months (n=10) after initiation of teriparatide treatment. Prior to biopsy, patients were labeled with tetracycline in a 3:14:3:5 day schedule. Longitudinal changes were assessed in the cancellous, endocortical, intracortical, and periosteal envelopes using a standard panel of histomorphometric indices. Representative images were taken with standard light microscopy and UV light illumination.

SHOTZ MINERALIZATION STUDY

To evaluate bone mineralization density distribution, quantitative backscattered electron imaging (qBEI) of transiliac crest bone biopsies was conducted in the SHOTZ study, a phase 4 randomized, active-comparator-controlled, bone biopsy study. Transiliac crest bone biopsies were obtained from ambulatory postmenopausal women with osteoporosis (age 55-89) at 6 months (n=28) or 24 months (n=10) after initiation of teriparatide treatment. qBEI is based on a quantification of the intensity of electrons backscattered from the surface of a sectioned bone area. The obtained signal is proportional to the weight fraction of calcium present locally in the bone tissue. qBEI images are from the 6 and 24 month transiliac crest bone biopsies from a representative patient treated with FORTEO. Mineral content in the bone tissue is visualized on a grey pixelated scale; darker areas represent areas with lower mineral content. Scale bars = 250 µm.

FORTEO SELECT SAFETY INFORMATION

The most common adverse reactions in clinical trials include: arthralgia (10.1% FORTEO vs. 8.4% placebo), pain (21.3% FORTEO vs. 20.5% placebo), and nausea (8.5% FORTEO vs. 6.7% placebo). Other adverse reactions include: dizziness, leg cramps, joint aches, and injection site reactions.

REFERENCES

2. FORTEO Prescribing Information 3. Riggs BL, Parfitt AM. J Bone Miner Res. 2005;20:177-184. 4. Raggatt LJ, Partridge NC. J Biol Chem. 2010;285:25103-25108. 5. Seeman E. Rheumatology (Oxford). 2008;47:iv2-iv8. 6. Dempster DW, et al. J Clin Endocrinol Metab. 2016;101:1353-1363. 7. Dempster DW, et al. J Bone Miner Res. 2016;31:1429-1439. 8. Dempster DW, et al. J Bone Miner Res. 2016; 31(8):1527-1535.

INDICATIONS, SAFETY INFORMATION AND BOXED WARNING

INDICATIONS AND USAGE

FORTEO is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture, and for the treatment of men and women with osteoporosis associated with sustained, systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture

High risk for fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy

FORTEO is administered as a 20-microgram once-daily dose and is available in a 2.4-mL prefilled delivery device for subcutaneous injection over 28 days.

It is not known if FORTEO reduces the risk of fracture in men. Consistent with the FORTEO Prescribing Information, fracture data in patients with glucocorticoid-induced osteoporosis are not shown.

IMPORTANT SAFETY INFORMATION FOR FORTEO

WARNING: POTENTIAL RISK OF OSTEOSARCOMA

In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times the exposure in humans given a 20-mcg dose. Because of the uncertain relevance of the rat osteosarcoma finding to humans, prescribe FORTEO® (teriparatide [rDNA origin] injection) only for patients for whom the potential benefits are considered to outweigh the potential risk. FORTEO should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, or prior external beam or implant radiation therapy involving the skeleton).

CONTRAINDICATIONS

Hypersensitivity to teriparatide or to any of its excipients. Reactions have included angioedema and anaphylaxis.

WARNINGS AND PRECAUTIONS

  • The following categories of patients have increased baseline risk of osteosarcoma and therefore should not be treated with FORTEO: Paget’s disease of bone, pediatric populations and young adults with open epiphyses, or prior external beam or implant radiation therapy.
  • Patients should be encouraged to enroll in the voluntary FORTEO Patient Registry, which is designed to collect information about any potential risk of osteosarcoma in patients who have taken FORTEO. Enrollment information can be obtained by calling 1-866-382-6813, or by visiting www.forteoregistry.rti.org.
  • Cases of bone tumor and osteosarcoma have been reported rarely in people taking FORTEO in the post-marketing period. The causality to FORTEO use is unclear.
  • The safety and efficacy of FORTEO have not been evaluated beyond 2 years of treatment. The use of FORTEO for more than 2 years during a patient’s lifetime is, therefore, not recommended.
  • Patients with the following conditions also should not receive FORTEO: bone metastases or a history of skeletal malignancies, metabolic bone diseases other than osteoporosis, or hypercalcemic disorders.
  • FORTEO may increase serum calcium, urinary calcium, and serum uric acid.
  • Use with caution in patients with active or recent urolithiasis because of risk of exacerbation. If active urolithiasis or pre-existing hypercalciuria are suspected, measurement of urinary calcium excretion should be considered.
  • Transient orthostatic hypotension may occur with initial doses of FORTEO. In short-term clinical pharmacology studies, transient episodes of symptomatic orthostatic hypotension were observed in 5% of patients. FORTEO should be administered initially under circumstances where the patient can sit or lie down if symptoms of orthostatic hypotension occur.
  • Patients receiving digoxin should use FORTEO with caution because FORTEO may transiently increase serum calcium and hypercalcemia may predispose patients to digitalis toxicity.

ADVERSE REACTIONS

The most common adverse reactions in clinical trials include: arthralgia (10.1% FORTEO vs. 8.4% placebo), pain (21.3% FORTEO vs. 20.5% placebo), and nausea (8.5% FORTEO vs. 6.7% placebo). Other adverse reactions include: dizziness, leg cramps, joint aches, and injection site reactions.

USE IN PREGNANCY/NURSING MOTHERS

  • FORTEO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Based on animal studies, FORTEO may cause fetal harm.
  • It is not known whether teriparatide is excreted in human milk. Breastfeeding mothers should discontinue nursing or FORTEO, taking into account the importance of treatment to the mother.

INSTRUCTIONS FOR FORTEO USE

FORTEO is provided as a fixed-dose, prefilled delivery device that can be used for up to 28 days, including the first injection. The delivery device contains 28 daily doses of 20 mcg each. Do not transfer the contents of the delivery device into a syringe. The FORTEO Delivery Device should be stored under refrigeration at 36° to 46° F (2° to 8° C) at all times. Do not use FORTEO if it has been frozen.

TE HCP ISI 24SEP2012

For more safety information, please see Medication Guide and Prescribing Information, including Boxed Warning regarding osteosarcoma. See User Manual that accompanies the delivery device.

INDICATIONS, SAFETY INFORMATION AND BOXED WARNING

MORE
LESS

INDICATIONS AND USAGE

FORTEO is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture, and for the treatment of men and women with osteoporosis associated with sustained, systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture

High risk for fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy

FORTEO is administered as a 20-microgram once-daily dose and is available in a 2.4-mL prefilled delivery device for subcutaneous injection over 28 days.

It is not known if FORTEO reduces the risk of fracture in men. Consistent with the FORTEO Prescribing Information, fracture data in patients with glucocorticoid-induced osteoporosis are not shown.

IMPORTANT SAFETY INFORMATION FOR FORTEO

WARNING: POTENTIAL RISK OF OSTEOSARCOMA

In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times the exposure in humans given a 20-mcg dose. Because of the uncertain relevance of the rat osteosarcoma finding to humans, prescribe FORTEO® (teriparatide [rDNA origin] injection) only for patients for whom the potential benefits are considered to outweigh the potential risk. FORTEO should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, or prior external beam or implant radiation therapy involving the skeleton).

CONTRAINDICATIONS

Hypersensitivity to teriparatide or to any of its excipients. Reactions have included angioedema and anaphylaxis.

WARNINGS AND PRECAUTIONS

The following categories of patients have increased baseline risk of osteosarcoma and therefore should not be treated with FORTEO: Paget’s disease of bone, pediatric populations and young adults with open epiphyses, or prior external beam or implant radiation therapy.

Patients should be encouraged to enroll in the voluntary FORTEO Patient Registry, which is designed to collect information about any potential risk of osteosarcoma in patients who have taken FORTEO. Enrollment information can be obtained by calling 1-866-382-6813, or by visiting www.forteoregistry.rti.org.

Cases of bone tumor and osteosarcoma have been reported rarely in people taking FORTEO in the post-marketing period. The causality to FORTEO use is unclear.

The safety and efficacy of FORTEO have not been evaluated beyond 2 years of treatment. The use of FORTEO for more than 2 years during a patient’s lifetime is, therefore, not recommended.

Patients with the following conditions also should not receive FORTEO: bone metastases or a history of skeletal malignancies, metabolic bone diseases other than osteoporosis, or hypercalcemic disorders.

FORTEO may increase serum calcium, urinary calcium, and serum uric acid.

Use with caution in patients with active or recent urolithiasis because of risk of exacerbation. If active urolithiasis or pre-existing hypercalciuria are suspected, measurement of urinary calcium excretion should be considered.

Transient orthostatic hypotension may occur with initial doses of FORTEO. In short-term clinical pharmacology studies, transient episodes of symptomatic orthostatic hypotension were observed in 5% of patients. FORTEO should be administered initially under circumstances where the patient can sit or lie down if symptoms of orthostatic hypotension occur.

Patients receiving digoxin should use FORTEO with caution because FORTEO may transiently increase serum calcium and hypercalcemia may predispose patients to digitalis toxicity.

ADVERSE REACTIONS

The most common adverse reactions in clinical trials include: arthralgia (10.1% FORTEO vs. 8.4% placebo), pain (21.3% FORTEO vs. 20.5% placebo), and nausea (8.5% FORTEO vs. 6.7% placebo). Other adverse reactions include: dizziness, leg cramps, joint aches, and injection site reactions.

USE IN PREGNANCY/NURSING MOTHERS

FORTEO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Based on animal studies, FORTEO may cause fetal harm.

It is not known whether teriparatide is excreted in human milk. Breastfeeding mothers should discontinue nursing or FORTEO, taking into account the importance of treatment to the mother.

INSTRUCTIONS FOR FORTEO USE

FORTEO is provided as a fixed-dose, prefilled delivery device that can be used for up to 28 days, including the first injection. The delivery device contains 28 daily doses of 20 mcg each. Do not transfer the contents of the delivery device into a syringe. The FORTEO Delivery Device should be stored under refrigeration at 36° to 46° F (2° to 8° C) at all times. Do not use FORTEO if it has been frozen.

TE HCP ISI 24SEP2012

For more safety information, please see Medication Guide and Prescribing Information, including Boxed Warning regarding osteosarcoma. See User Manual that accompanies the delivery device.