Table of Contents
Teriparatide Injection (rDNA origin)
Fortéo Teriparatide Injection (rDNA origin)
Teriparatide Injection (rDNA origin)
Teriparatide Injection (rDNA origin)
Regulatory History
Regulatory History
Lilly Advisory Committee Presentation Fortéo 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 µg
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 µg 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 µg
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 µg
Clinical Efficacy Teriparatide 20 µg
Clinical Safety Teriparatide 20 µg
Conclusions
PPT Slide
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