Drug Discovery in Japan: Investigating the Sources of Innovation

Book Overview

Foreword

Acknowledgement

Chapter 1: Introduction

1.1 Objectives

1.2 Drugs discussed in the case studies

References

Chapter 2: Compactin

The discovery of statin, "penicillin" for cholesterol

Abstract

2.1 Introduction

2.2 Timeline of the discovery and development of compactin

2.3 Statin discovery program

2.4 Novelty of the Endo's discovery program

2.5 Collaboration with academia

Box 2.1 Academic-industrial collaboration to understand the mechanism of action of statin

2.6 Crises and discontinuations

2.6.1 First crisis: failure in rats

2.6.2 Second crisis: suspected hepatotoxicity

2.6.3 Third crisis: discontinuation of clinical development

2.7 Science sources that supported the discovery of compactin

2.8 Responses to discontinuation of the clinical trial

2.9 "Invisible" discovery competition

2.10 Compactin is the basis for all statins

2.11 Statin sales

2.12 Conclusion

References

Chapter 3: Pravastatin (Pravachol, Mevalotin) "Blockbuster" statin discovered from the metabolites of compactin

Abstract

3.1 Introduction

3.2 Characteristics of pravastatin

3.3 Timeline of R&D for pravastatin

3.4 Discovery of pravastatin: from the metabolites of compactin

3.5 Pre-clinical studies using WHHL rabbits

3.6 Development of a two-step fermentation production process

3.7 Five yeas from initiating clinical trials to the approval for human use

3.10 Global large-scale and long-term clinical studies

3.12 Clinical development through collaboration between industry and academia

3.11 Toward a blockbuster drug

3.12 Partnership with Bristol-Myers Squibb

Box 3.1 Statin development competition: Sankyo vs Merck

3.13 Conclusion

References

Chapter 4: Rosuvastatin(Crestor) "Super statin" which became a global block buster despite its late entry

Abstract

4.1 Introduction

4.2 Timeline of rosuvastatin synthesis and development

4.3 Discontinuation of the Clinical Trial by Shionogi

4.4 AstraZeneca resumed clinical trials

4.5 Sources of discovery: fluvastatin as the lead compound

4.6 Crestor sales: Peak sales exceed 7.1 billion USD

4.7 Rosuvastatin vs atorvastatin

4.8 Properties of commercially available statins

4.9 Economic value of follow-on innovation

Box 4.1

• Format: Paperback
• Language: English
• ISBN: 981138908X
• ISBN13: 9789811389085
• Release Date: November 2020
• Publisher: Springer
• Length: 333 Pages
• Weight: 1.09 lbs.
• Dimensions: 0.7" x 6.1" x 9.2"