Teriparatide Injection (rDNA origin)

7/31/01


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Table of Contents

Teriparatide Injection (rDNA origin)

Forto Teriparatide Injection (rDNA origin)

Teriparatide Injection (rDNA origin)

Teriparatide Injection (rDNA origin)

Regulatory History

Regulatory History

Lilly Advisory Committee Presentation Forto Teriparatide Injection (rDNA origin)

External Consultants

History, Mechanism of Action, and Clinical Need

Chronology of Advances in PTH Research

Effects of PTH(1-34) on Bone Mineral Density in Postmenopausal Women and in Men

Change in Lumbar Spine BMD

Change in Total Hip BMD

Effect of PTH + HRT vs. HRT Alone on Vertebral Fractures at 3 Years

Response to PTH(1-34) Histomorphometry After 4 Weeks

Early Changes in Biochemical Markers in Women with Osteoporosis on PTH(1-34)

Bone Structure: 3-D

64 Year-Old Woman (M H)

Clinical Need for New Osteoporosis Treatment

Limitations of Current Therapies: Many Patients Remain at Significant Risk

Relative Risk of Death Following Clinical Fractures Fracture Intervention Trial (FIT)*

Clinical Need in Osteoporosis

Conclusion

Nonclinical Overview

Nonclinical Overview

Teriparatide Increases Bone Mass and Improves Architecture in Ovariectomized Monkeys

Cortical Bone Quality is Normal in Monkeys Treated with Teriparatide

Nonclinical Safety

Comparison of Cynomolgus Monkey Models

Nonclinical Safety

Exaggerated Increases in Bone Mass 2-year Rat Study

Rat Skeleton Has An Exaggerated Response To Teriparatide Treatment

2-Year Rat Study Incidence of Bone Proliferative Lesions (n=60/sex/group)

Important Findings 2-Year Rat Study

Rat Findings are Unlikely to be Predictive of an Increased Risk of Osteosarcoma in Humans Treated with Teriparatide for Osteoporosis

Rat Findings are Unlikely to be Predictive of an Increased Risk of Osteosarcoma in Humans Treated with Teriparatide for Osteoporosis

Rat Findings are Unlikely to be Predictive of an Increased Risk of Osteosarcoma in Humans Treated with Teriparatide for Osteoporosis

Rat Findings are Unlikely to be Predictive of an Increased Risk of Osteosarcoma in Humans Treated with Teriparatide for Osteoporosis

Rat Findings are Unlikely to be Predictive of an Increased Risk of Osteosarcoma in Humans Treated with Teriparatide for Osteoporosis

Rat Findings are Unlikely to be Predictive of an Increased Risk of Osteosarcoma in Humans Treated with Teriparatide for Osteoporosis

Nonclinical Conclusions

Clinical Efficacy

Teriparatide Clinical Trials

Teriparatide Treatment Trials and Follow-up

Pivotal Trial in Women Study GHAC

Baseline Characteristics - GHAC

Duration of Study GHAC (From randomization to last radiograph)

Semiquantitative Evaluation of Vertebral Fractures

Teriparatide Reduces the Risk of Vertebral Fractures - GHAC

Teriparatide Reduced the Risk of Moderate and Severe Vertebral Fractures - GHAC

Teriparatide Reduced the Risk of Multiple Vertebral Fractures - GHAC

Teriparatide Reduced Nonvertebral Fragility Fractures - GHAC

Time to First Nonvertebral Fragility Fracture GHAC

Teriparatide Increased Lumbar Spine BMD - GHAC

Teriparatide Increased Hip BMD GHAC

Teriparatide Effects on Forearm BMD GHAC

Teriparatide Increased Total Body Bone Mineral - GHAC

Histologically Normal Bone Study GHAC

Teriparatide Produces Beneficial Effects on Bone Study GHAC

Pivotal Trial in Women GHAC Summary

Pivotal Trial in Men Study GHAJ

Baseline Characteristics - GHAJ

Duration of Study GHAJ (From randomization to last BMD)

Teriparatide Increased Lumbar Spine BMD GHAJ

Teriparatide Effects on Hip BMD GHAJ (Baseline to Endpoint)

Teriparatide Increased Total Body Bone Mineral - GHAJ

Pivotal Trial in Men Study GHAJ Summary

Change in Spine BMD for Women and Men - GHAC and GHAJ Teriparatide 20 ?g

Mean Change in Hip BMD for Women and Men - GHAC and GHAJ Teriparatide 20 g

Efficacy Summary

Clinical Safety

Overview

Total Experience and Exposure

Overall Clinical Safety Pivotal Trials in Women and in Men Studies GHAC and GHAJ

Clinical Safety Evaluations

Treatment-Related Effects GHAC

Pharmacokinetic and Safety Laboratory Evaluations

Teriparatide 20 g Pharmacokinetics GHAC

Pharmacologic Effect: Transient Increase in Serum Calcium - GHAC

Postdose Effects on Serum Calcium are Small and Transient - GHAC

Pharmacologic Effect: Predose Serum Calcium - GHAC

Pharmacologic Effect: 30 mg/day Increase in 24-Hour Urinary Calcium Excretion - GHAC

Serum and Urinary Calcium Summary - GHAC

Pharmacologic Effect: Serum Uric Acid - GHAC

Incidence of Gout or Arthralgia Was Not Increased - GHAC

No Significant Increase in Conditions Associated with Hyperparathyroidism Study GHAC

No Adverse Effects on the Kidney Study GHAC

Hemodynamic Evaluations Teriparatide 20 g

Clinical and Laboratory Effects After Discontinuation of Treatment

Ongoing Follow-up Study GHBJ

Clinical and Laboratory Effects After Discontinuation of Treatment Study GHAC-GHBJ

Clinical and Laboratory Effects After Discontinuation of Treatment Study GHAC-GHBJ

No Increase in Nonvertebral Fractures After Discontinuation of Treatment (GHAC-GHBJ)

Treatment of Osteoporosis in Men

Clinical and Laboratory Safety Evaluations - GHAJ

Similar Treatment Effects in Women and in Men Studies GHAC and GHAJ

Vertebral Fracture Incidence in Men During Treatment and Follow-Up (GHAJ-GHBJ)

No Clinically Significant Pharmacokinetic or Safety Issues in Special Populations Studied

No Clinically Significant Drug Interactions

Safety Summary Pivotal Phase 3 Trials

Safety Summary Pivotal Phase 3 Trials

Safety Summary Post-treatment Follow-up Study GHBJ

Safety Conclusions

Teriparatide Summary and Conclusions

PTH Oncology Board

PTH Oncology Board Summary

Additional Considerations Regarding Rat Osteosarcoma Findings

Risk Communication

Post-Approval Safety Surveillance Program

Teriparatide Improves Skeletal Architecture

Dose Selection

Clinical Efficacy Teriparatide 20 g

Clinical Efficacy Teriparatide 20 g

Clinical Safety Teriparatide 20 g

Conclusions

PPT Slide

Author: m e perron