Osteoporosis Therapy Overview

2,552 views

Published on

Published in: Health & Medicine, Business
0 Comments
4 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,552
On SlideShare
0
From Embeds
0
Number of Embeds
11
Actions
Shares
0
Downloads
103
Comments
0
Likes
4
Embeds 0
No embeds

No notes for slide

Osteoporosis Therapy Overview

  1. 1. Osteoporosis Luke LightningLuke Lightning, PhD
  2. 2. Osteoporosis• Affects >10 million people in the US – 8 million women – Another 34 million are at risk – Number of fractures increased 55% since 1995• > 20 drugs approved for this condition• Low bone mass and bone deterioration –  increase in risk of fracture Medications – 1.5 million fractures/year – Hip, spine, wrist• No known cure 2
  3. 3. Who is At Risk for Osteoporosis? “Really Naked Calendar” - UKPostmenopausal women 3
  4. 4. Universal Prevention Measures Some ways you can minimize risk of fractures: • avoid clothing that increases risk of fall • ingest > 1200 mg of calcium/day • supplement diet with 700-800 IU/day of vitamin D • exercise regularly •wear clothing that protects against fracturesConfidential 4
  5. 5. Bone Remodeling Dynamic processOsteoclasts: break down bone Osteoblasts: build bone Confidential 5
  6. 6. Confidential 6
  7. 7. Risk Factors for Osteoporosis• Old age – Postmenopausal women • Lose bone 2-4 X faster Primary • Estrogen deficiency  increased bone resorption Osteoporosis• Sedentary lifestyle• Genetics• Hormonal disorders Secondary• Smoking and alcoholism Osteoporosis• Diseases (e.g. celiac)• Medications (e.g. some cancer drugs) 7
  8. 8. Preclinical and Clinical Trial Considerations• Significant differences in bone mineral density among species• Ovariectomized rat model for postmenopausal osteoporosis• Phase III Clinical Trials – Proven fracture efficacy after 3 years – Endpoints: vertebral and non-vertebral fractures 8
  9. 9. Diagnostic Test• Bone densitometry scan – DEXA measures calcium •  T-score – FRAX  risk of fracture T-score: Comparison to young adult meanConfidential 9
  10. 10. Current Therapies and Market Selective EstrogenBisphosphonates: ModulatorsFosamax (SERMs): $10 billion market Evista (2010, projected) DenosumabPeptide Hormones: andForteo, Calcitonin Other Potential Targets 10
  11. 11. Sales• Fosamax has 50% market share – $3 billion, 16% of Merck’s total drug sales Bisphosphonates 11
  12. 12. Bisphosphonates• Considered to be the standard of care – Revolutionized treatment of osteoporosis (1960’s) – Fosamax (Merck, generic), Boniva (GSK, Roche) pharmacokinetics phosphonate phosphonate efficacy 12
  13. 13. Bisphosphonates• Can reduce risk of fracture by 40-50% over 3-5 years• Very high affinity for and rapid absorption to bone tissue• Inhibit osteoclast bone resorption• Dosing intervals vary: – Orally on a daily or weekly basis – Monthly – Once yearly IV infusion• Compliance is 25-40% after 1 year• Major side effect: – Osteonecrosis of the jaw• Cost: $400/year (Fosamax), $2,000/year (Boniva) 13
  14. 14. Calcium Homeostasis• Calcitonin vs. Parathyroid Hormone Calcium deposited Into bone 14
  15. 15. Salmon Calcitonin• 32 amino acid peptide• Open IND for oral calcitonin (Bone Medical Ltd., Australia) – Phase III pathway identified More active than human form 15
  16. 16. Teriparatide (Forteo)• 34 amino acid analog of parathyroid hormone• 20 µg s.c. once/day – Thigh or abdomen Parathyroid hormone• Enhances bone strength and size Teriparatide – Intermittent exposure •  activates osteoblasts > osteoclasts – Chronic exposure •  enhances bone resorption • 2nd line therapy • Only used for 2 years• Major side effect: bone cancer (in rats)• Cost: $7,000/year 16
  17. 17. Raloxifene (Evista)• Selective Estrogen Receptor Modulator (SERM)• Orally administered• Effective in women only• Reduced risk of vertebral fracture by 30-50% – Higher incidence of stroke – Teratogen• Cost: >$1,000/year• August 2009: Lilly dropped Arzoxifene – Did not meet secondary endpoints – More frequent adverse events 17
  18. 18. Prolia (Denosumab)• Biologic from Amgen supposedly better than others because: – Targeted mechanism – RANKL inhibitor • Inhibits formation and function of osteoclasts – Improved dosing schedule • s.c. once every 6 months – Superior tolerability – Reduced fracture risk by 68% – Cost >$10,000/year• August 2009 FDA panel: – Data from 30 clinical trials – Only 2 of 6 indications • Safety issues 18
  19. 19. Other Potential Targets or Products In Development (2008)>16 Targets> 40 Products 19
  20. 20. Cats purr to strengthen their bones!! 20
  21. 21. Whole Body Vibration and Effects on Bone• Potential Benefit of vibration therapy: – Astronauts: bone density loss and muscle atrophy are a serious concern at zero gravity for extended periods of time – Postmenopausal women: ~100 patient study, 6 month (2008) • 30 Hz, 5X/week for 10 min  • reduced back pain and increased femoral neck (3.2%) and lumbar BMD (4.3%)• Cat purring: – Frequency = 25-150 Hz  improve bone density and healing – Low energy mechanism that stimulates muscles and bones – Potential source of self-healing 21
  22. 22. New Therapy?● Leather Vibrating Massage Chair with Cooler Milk 22
  23. 23. Osteoporosis Summary• Very large patient population and large market – Affects 75 million people in the US, Europe, and Japan• Bone tissue is dynamic and undergoes constant remodeling• Several current therapies – Can slow the progression of the disease, but no known cure – Significant side effects – At least 15 potential targets under investigation • Stem Cells• Crazy cat lady may be not so crazy! 23

×