CLINICAL TRIALS PROFILE FOR TERIPARATIDE RECOMBINANT HUMAN

All Clinical Trials for Teriparatide Recombinant Human

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000400 ↗	Alendronate and/or Parathyroid Hormone for Osteoporosis	Completed	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)	Phase 2	1999-08-01	This study looks at the effects of two medications, alendronate and parathyroid hormone, on bone mass and on bone formation and bone breakdown in women with osteoporosis. We will randomly select postmenopausal women who have osteoporosis to receive laboratory-produced human parathyroid hormone (hPTH), or alendronate, or both for 2.5 years. Study participants will return to the study center periodically to have their bone mass measured and to give blood and urine samples for tests of bone formation and breakdown and for other laboratory tests. Those who complete the study are eligible for one or two 12 month extension studies.
NCT00000400 ↗	Alendronate and/or Parathyroid Hormone for Osteoporosis	Completed	Massachusetts General Hospital	Phase 2	1999-08-01	This study looks at the effects of two medications, alendronate and parathyroid hormone, on bone mass and on bone formation and bone breakdown in women with osteoporosis. We will randomly select postmenopausal women who have osteoporosis to receive laboratory-produced human parathyroid hormone (hPTH), or alendronate, or both for 2.5 years. Study participants will return to the study center periodically to have their bone mass measured and to give blood and urine samples for tests of bone formation and breakdown and for other laboratory tests. Those who complete the study are eligible for one or two 12 month extension studies.
NCT00005006 ↗	Parathyroid Hormone (PTH) With Alendronate for Osteoporosis	Completed	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)	Phase 2	1987-09-01	This study investigates the effectiveness of parathyroid hormone (PTH) in combination with alendronate, a standard treatment for osteoporosis that blocks or reduces bone loss. We are using alendronate because it may help protect patients against any possible harmful effects of PTH in cortical bone such as the long bones or hip. We are testing two different treatment schedules of PTH-one in which we give PTH daily and one in which we give PTH for 3 out of every 6 months in a cyclical fashion. The entire study is 21 months long; the active treatment period is 18 months with a 6-month followup period. The main effects we will look for in this study are changes in body chemicals that are signs of bone formation or bone breakdown, and changes in bone density throughout the skeleton. We will randomly assign all study participants, who are women aged 50 and over, to either stay on alendronate alone, receive daily continuous PTH plus alendronate, or receive daily PTH for 3 months out of every 6 for a total of three separate 3-month cycles of PTH plus daily alendronate.
NCT00005006 ↗	Parathyroid Hormone (PTH) With Alendronate for Osteoporosis	Completed	Helen Hayes Hospital	Phase 2	1987-09-01	This study investigates the effectiveness of parathyroid hormone (PTH) in combination with alendronate, a standard treatment for osteoporosis that blocks or reduces bone loss. We are using alendronate because it may help protect patients against any possible harmful effects of PTH in cortical bone such as the long bones or hip. We are testing two different treatment schedules of PTH-one in which we give PTH daily and one in which we give PTH for 3 out of every 6 months in a cyclical fashion. The entire study is 21 months long; the active treatment period is 18 months with a 6-month followup period. The main effects we will look for in this study are changes in body chemicals that are signs of bone formation or bone breakdown, and changes in bone density throughout the skeleton. We will randomly assign all study participants, who are women aged 50 and over, to either stay on alendronate alone, receive daily continuous PTH plus alendronate, or receive daily PTH for 3 months out of every 6 for a total of three separate 3-month cycles of PTH plus daily alendronate.
NCT00035256 ↗	Sequential Use of Teriparatide and Raloxifene HCl in the Treatment of Postmenopausal Women With Osteoporosis	Completed	Eli Lilly and Company	Phase 4	2001-10-01	The purpose of this study is to determine whether the increase in spine bone mineral density that has been generally observed in previous clinical studies involving the study drug can be maintained or even increased if followed with raloxifene HCl. All qualifying study participants will receive the study drug followed by treatment with raloxifene HCl or placebo. All study participants will receive raloxifene HCl in the third phase of the study.

Clinical Trial Conditions for Teriparatide Recombinant Human

Condition Name

Condition Name for Teriparatide Recombinant Human
Intervention	Trials
Osteoporosis	67
Osteoporosis, Postmenopausal	13
Postmenopausal Osteoporosis	11
Osteoporosis, Post-menopausal	5

Condition MeSH

Condition MeSH for Teriparatide Recombinant Human
Intervention	Trials
Osteoporosis	103
Osteoporosis, Postmenopausal	32
Fractures, Bone	19
Bone Diseases, Metabolic	8

Clinical Trial Locations for Teriparatide Recombinant Human

Trials by Country

Trials by Country for Teriparatide Recombinant Human
Location	Trials
United States	251
Canada	38
Denmark	14
Spain	12
Germany	12

Trials by US State

Trials by US State for Teriparatide Recombinant Human
Location	Trials
New York	22
Georgia	13
Nebraska	13
Pennsylvania	13
Massachusetts	13

Clinical Trial Progress for Teriparatide Recombinant Human

Clinical Trial Phase

Clinical Trial Phase for Teriparatide Recombinant Human
Clinical Trial Phase	Trials
Phase 4	47
Phase 3	31
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for Teriparatide Recombinant Human
Clinical Trial Phase	Trials
Completed	95
Recruiting	17
Unknown status	11

Clinical Trial Sponsors for Teriparatide Recombinant Human

Sponsor Name

Sponsor Name for Teriparatide Recombinant Human
Sponsor	Trials
Eli Lilly and Company	51
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)	8
Massachusetts General Hospital	7

Sponsor Type

Sponsor Type for Teriparatide Recombinant Human
Sponsor	Trials
Other	149
Industry	87
NIH	19

Teriparatide: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction

Teriparatide, a recombinant human parathyroid hormone (PTH) analog, has been a significant player in the treatment of osteoporosis since its FDA approval in 2002. This article provides an in-depth look at the clinical trials, market analysis, and future projections for this potent anabolic agent.

Clinical Trials and Efficacy

Bone Formation and Density

Teriparatide, specifically the 1-34 amino-acid fragment of human PTH, is known for its ability to stimulate bone formation, increase bone mineral density (BMD), and restore bone architecture and integrity. Clinical trials have consistently shown that teriparatide outperforms bisphosphonates like alendronate in these aspects. For instance, a randomized double-blind trial involving postmenopausal women with osteoporosis demonstrated that teriparatide increased lumbar spine BMD by 12.2% compared to a 5.6% increase with alendronate over 14 months[1].

Fracture Prevention

The efficacy of teriparatide in reducing fracture risk is well-documented. Studies have shown that teriparatide significantly reduces the incidence of both vertebral and nonvertebral fractures. In a placebo-controlled trial, once-daily administration of teriparatide for 19 months substantially reduced the risks of fractures compared to placebo-treated patients[1].

Comparison with Alendronate

When compared to alendronate, teriparatide has shown superior outcomes in several clinical trials. For example, in a study involving postmenopausal women, teriparatide increased femoral neck BMD and total body bone mineral more significantly than alendronate. Additionally, the nonvertebral fracture incidence was lower in the teriparatide group[1].

Glucocorticoid-Induced Osteoporosis

Teriparatide has also been approved for the treatment of osteoporosis associated with sustained systemic glucocorticoid therapy. Clinical trials have shown that teriparatide increases BMD at the lumbar spine and reduces vertebral fracture risk more effectively than alendronate in this patient population[3].

Market Analysis

Cost-Effectiveness

Despite its efficacy, teriparatide is more expensive than traditional treatments like alendronate. Cost-effectiveness analyses have shown that teriparatide alone is less cost-effective than alendronate, but sequential therapy with teriparatide followed by alendronate can be more cost-effective at certain price points. For instance, at 25% of its base price, sequential teriparatide/alendronate therapy costs $11,400 per quality-adjusted life-year (QALY) compared to usual care[2].

Market Trends and Sales

Teriparatide has seen significant market traction since its approval. In 2005, it generated worldwide sales of over $350 million, with projected annual sales approaching $750 million by 2007-2008[2]. The drug's market performance is driven by its unique mechanism of action and the growing demand for effective osteoporosis treatments.

Safety and Adverse Events

Osteosarcoma Risk

Initially, there were concerns about the risk of osteosarcoma associated with teriparatide, based on findings in Fischer 344 rats. However, extensive postmarketing surveillance and human studies have found no increased risk of osteosarcoma in humans. The FDA has since removed the boxed warning regarding osteosarcoma risk from the drug's label[3].

Adverse Event Profile

Data from the FDA's Adverse Event Reporting System (FAERS) indicate that the most common adverse events associated with teriparatide include musculoskeletal and connective tissue disorders, as well as general disorders and administration site conditions. Serious adverse events leading to hospitalization or prolongation of hospitalization are also reported, although less frequently[4].

Label Changes and Long-Term Use

Extended Treatment Duration

Historically, teriparatide was limited to 24 months of lifetime use due to concerns about osteosarcoma. However, with no evidence of increased osteosarcoma risk in humans, the FDA has removed this limitation. Clinicians now consider long-term use in high-risk patients, particularly those on long-term glucocorticoid therapy or with elevated bone-formation markers[3].

Identifying Patients for Long-Term Use

Patients who may benefit from long-term teriparatide administration include those with high fracture risk, current glucocorticoid users, and those with elevated levels of the bone-formation marker pro-collagen type 1 N-terminal propeptide (P1NP) after 2 years of treatment. Continuing therapy as long as P1NP levels remain elevated and the patient has not had new vertebral compression fractures is recommended[3].

Market Projections and Future Outlook

Growing Demand

The demand for effective osteoporosis treatments is expected to grow, driven by an aging population and increasing awareness of osteoporosis. Teriparatide, with its unique anabolic mechanism, is well-positioned to capture a significant share of this market.

Competitive Landscape

While bisphosphonates remain the most commonly prescribed osteoporosis medications, teriparatide's ability to stimulate new bone formation makes it an attractive option for patients who have failed or are intolerant to other treatments. The removal of the boxed warning and the potential for long-term use further enhance its market prospects.

Research and Development

Ongoing and future clinical investigations are expected to explore the potential additional benefits of longer-term use of teriparatide and other anabolic agents. This could lead to expanded indications and improved treatment protocols, further solidifying teriparatide's place in the osteoporosis treatment market.

Key Takeaways

• Efficacy: Teriparatide significantly increases BMD and reduces fracture risk, outperforming bisphosphonates in clinical trials.
• Cost-Effectiveness: While more expensive than alendronate, sequential teriparatide/alendronate therapy can be cost-effective at certain price points.
• Safety: No increased risk of osteosarcoma in humans; common adverse events include musculoskeletal and general disorders.
• Label Changes: FDA has removed the 24-month treatment limit, allowing for long-term use in high-risk patients.
• Market Projections: Growing demand for osteoporosis treatments and teriparatide's unique mechanism position it for continued market growth.

FAQs

What is teriparatide used for?

Teriparatide is used for the treatment of postmenopausal women with osteoporosis at high risk for fracture, men with primary or hypogonadal osteoporosis, and individuals with osteoporosis associated with sustained systemic glucocorticoid therapy[5].

How does teriparatide work?

Teriparatide works by stimulating bone formation, increasing bone mineral density, and restoring bone architecture and integrity. It is an anabolic agent, unlike bisphosphonates which reduce bone resorption[1].

Is teriparatide safe?

Extensive postmarketing surveillance has found no increased risk of osteosarcoma in humans. Common adverse events include musculoskeletal and connective tissue disorders, as well as general disorders and administration site conditions[3][4].

Can teriparatide be used long-term?

Yes, the FDA has removed the 24-month treatment limit, and clinicians consider long-term use in high-risk patients, particularly those on long-term glucocorticoid therapy or with elevated bone-formation markers[3].

How does teriparatide compare to alendronate?

Teriparatide increases BMD and reduces fracture risk more significantly than alendronate in clinical trials. However, teriparatide is more expensive and may not be as cost-effective in all scenarios[1][2].

What are the common adverse events associated with teriparatide?

Common adverse events include musculoskeletal and connective tissue disorders, general disorders, and administration site conditions. Serious adverse events leading to hospitalization or prolongation of hospitalization are also reported[4].

Sources

1. Neer, R. M., et al. "Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis." Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 10, 2002, pp. 4528-4538.
2. Cummings, S. R., et al. "The cost-effectiveness of therapy with teriparatide and alendronate in women with severe osteoporosis." JAMA Internal Medicine, vol. 168, no. 11, 2008, pp. 1175-1183.
3. Lindsay, R., et al. "Teriparatide: Label changes and identifying patients for long-term use." Cleveland Clinic Journal of Medicine, vol. 88, no. 9, 2021, pp. 489-496.
4. Zhang, Y., et al. "Indications and adverse events of teriparatide: based on FDA Adverse Event Reporting System (FAERS)." Frontiers in Pharmacology, vol. 15, 2024, pp. 1-12.
5. DrugBank. "Teriparatide: Uses, Interactions, Mechanism of Action." DrugBank, 2023.