FORTEO (teriparatide [rDNA origin] injection) Efficacy: In a median of 19 months, FORTEO significantly reduced the risk of vertebral and nonvertebral fractures*†2

In a median of 19 months, FORTEO Significantly Reduced the Risk of Vertebral and Nonvertebral Fractures

Number needed to treat11= 11
n=448 (placebo); with ≥1 new vertebral fracture(s): 64
n=444 (FORTEO); with ≥1 new vertebral fracture(s): 22
(RR, 0.35; 95% CI, 0.22—0.55)
(AR: placebo 14.3%; FORTEO 5.0%, P≤0.001)

Number needed to treat12 = 34
n=544 (placebo); with ≥1 new nonvertebral fracture(s): 30
n=541 (FORTEO); with ≥1 new nonvertebral fracture(s): 14
(RR, 0.47; 95% CI, 0.25—0.88)
(AR: placebo 5.5%; FORTEO 2.6%, P<0.05)

Approximately 90% of patients in the Fracture Prevention Trial had a prevalent vertebral fracture2

*Fracture Prevention Trial: Multicenter, prospective, double-blind trial of FORTEO 20 mcg/day (n=541) vs. placebo (n=544). 1,637 postmenopausal women with osteoporosis, of whom 90% had a prevalent vertebral fracture at baseline, were evaluated. Mean age: 69. Median duration of exposure to therapy: 19 months (maximum 24 months). All received 1,000 mg/day of calcium and 400-1,200 IU/day of vitamin D.2,9

**A post hoc analysis of the vertebral fracture data from the Fracture Prevention Trial using a combination of quantititive vertebral morphometry measurements (QM) and qualitative visual semiquantitative (SQ) grading to assess lateral spine radiographs showed that vertebral fracture relative risk reduction for FORTEO was 84%§14

§A post hoc analysis was conducted on a subset of 892 women who had a baseline and enpoint spine radiograph (FORTEO n-444, placebo n=448). Primary analysis was the comparison of the proportions of women with new vertebral fractures as defined by the combination of group-blinded quantitative vertebral morphometry measurements and confirmation of the results of qualitative visual semiquantitative grading by Neer et al, using a Fishers’ exact test.14

Nonvertebral fracture risk reduction was obtained from pooling data from the following sites: ankle/foot, hip, humerus, pelvis, ribs, wrist, and other sites.

Fragility fractures were defined as fractures occurring with minimal trauma (eg, falling from standing height).

FORTEO Select Safety Information

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. The clinical relevance of the rat osteosarcoma finding to humans is unknown.

FORTEO may help increase bone mineral density

In postmenopausal women with osteoporosis treated with FORTEO2*:

  • Hip and femoral neck BMD were significantly increased at endpoint
  • 96% had an increase in lumbar spine BMD
  • Lumbar spine BMD was significantly increased above baseline at 3 months through end point
Forteo increased lumbar spine BMD in postmenopausal women with osteoporosis
  • In a population of patients for whom data were available at every time point (FORTEO [n=129], placebo [n=137]), FORTEO significantly increased lumbar spine BMD by 11.8% at 18 months†10
  • In a separate analysis of the data using the last observation carried forward (FORTEO [n=541], placebo [n=544]), FORTEO significantly increased lumbar spine BMD by 9.7%‡2

Study Design

* Fracture Prevention Trial: Multicenter, prospective, double-blind trial of FORTEO 20 mcg/day (n=541) vs. placebo (n=544). 1,637 postmenopausal women with osteoporosis, of whom 90% had a prevalent vertebral fracture at baseline, were evaluated. Mean age: 69. Median duration of exposure to therapy: 19 months (maximum 24 months). All received 1,000 mg/day of calcium and 400—1,200 IU/day of vitamin D.2,9

P‹0.001 for FORTEO vs. placebo at each postbaseline time point.

P‹0.001 for FORTEO compared with placebo at endpoint.

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.

VERO – The first trial in osteoporosis research that has shown a significant vertebral fracture risk reduction outcome as a primary endpoint in a head-to-head, active comparator study.13

FORTEO® (teriparatide) demonstrated a statistically significant reduction in the incidence of new vertebral fragility fractures at 24 months vs a bisphosphonate.13

Forteo Vero Study & Incidence of new vertebral fractures graph

The effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO) trial. A multicenter, double-blind, double-dummy, randomized controlled trial of teriparatide (FORTEO) 20mcg/day (n=680) vs. risedronate 35mg once weekly (n=680). 1,366 postmenopausal women with severe osteoporosis (≥1 prevalent vertebral fracture at baseline) of whom 72.1% received at least one prior osteoporosis medication, most commonly a bisphosphonate, were enrolled. The mean age was 72.1. Median (IRQ) duration of therapy was 23.9 (18.8 to 24.1) months for FORTEO and 23.7 (22.8 to 24.0) months for risedronate. All patients received 500 - 1,000 mg/day of calcium and 400 - 800 IU/day of vitamin D.13

There were no statistically significant differences between the 2 groups in the proportion of patients with 1 or more treatment-emergent adverse events in VERO: ≥1 adverse event (72.8% FORTEO vs. 73.5% risedronate).13

The Fracture Prevention Trial, FORTEO’s pivotal trial, showed that, in a median of 19 months, FORTEO 20 mcg/day significantly reduced the risk of vertebral fracture by 9.3% ARR or 65% RRR vs placebo [FORTEO n=444, Placebo n=448]. Mean age: 69; 90% had prevalent vertebral fracture at baseline; all received 1,000 mg/day calcium and 400-1,200 IU/day vitamin D.9

The most common adverse reactions in FORTEO 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).9


References

2. FORTEO package insert. Indianapolis, IN: Eli Lilly and Company; 2012., 9. Neer RM, et al. N Engl J Med. 2001;344:1434-1441., 10. Data on file, Lilly Research Laboratories (FOR20090922A)., 11. Data on file, Lilly Research Laboratories (FOR20110608A)., 12. Data on file, Lilly Research Laboratories (FOR20111019A)., 13. Kendler DL et al. The Lancet 2017. DOI: https://doi.org/10.1016/S0140-6736(17)32137-2, 14. Prevrhal S. Curr Med Res Opin. 2009;25:921-928.

Indications and Important Safety Information Warning: Potential Risk of Osteosarcoma
Warning: Potential Risk of Osteosarcoma
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

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.

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

Forteo is a registered trademark owned or licensed by Eli Lilly & Company, its subsidiaries, or affiliates.
TE HCP ISI 24SEP2012