薬剤リポジショニング戦略

Abstract

Overview

Introduction

Drug repositioning has several advantages over traditional discovery-reduced cost, risk and time to market-compared with traditional discovery, providing an attractive prospect for Big Pharma, scrambling to fill pipelines in an increasingly harsh market environment. As competition to inlicense candidates drives the price of this strategy up, repositioning presents a cost effective alternative.

Scope

• An outline of what drug repositioning is, and what is driving it.
• An overview of the key players in the repositioning industry their methodologies and specialities.
• Case-studies describing a number of drugs which are or have been repositioned.
• An insight into how repositioning will change going forward.

Highlights

Despite increasing R&D investment, productivity has been declining, at a time when Big Pharma is contending with latestage pipeline failures and more rigorous drug approval procedures, in addition to external challenges in the form of generic competition and pricing pressures.

The cost savings, accelerated path to market, and lower risks that repositioning brings relative to traditional discovery are attractive to Big Pharma, which has thus far been filling pipeline gaps by inlicensing, a practice which has become more expensive as competition for candidates increases.

The companies involved in repositioning currently differ greatly in the methodologies used, in addition to their disease focus, however as the strategy gains traction, the industry is likely to undergo considerable consolidation.

Reasons to Purchase

• Understand what drug repositioning is, and why it is important.
• Become aware of who the key players in drug repositioning are and how they operate.
• Gain an insight into how drugs have been, and are being repositioned.

Table of Contents

• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the report
  • Key findings
• CHAPTER 2 OVERVIEW OF DRUG REPOSITIONING
  • Drug repositioning as a phenomenon distinct from lifecyclemanagement
  • The basis of repositioning
  • The motives for repositioning
    • Increased R&D investment has had little impact onproductivity
    • Greater hurdles to obtaining drug approval
    • Late-stage failures
  • Drug repositioning as a means of reducing risk, cost andtime-to-market
    • Conventional de novo drug development
    • The development of a repositioned drug is acceleratedrelative to a conventional candidate
  • A growing trend toward systematic rather thanserendipitous repositioning
    • Viagra (sildenafil) - from angina to impotence in oneserendipitous leap
    • Duloxetine' s dual role established through informedinsight
    • The success of sildenafil and duloxetine was facilitatedby the prevailing market environment
    • Informed insight could lead to diabetes drug for epilepsy
    • Thalidomide represents an unusual form of drugrepositioning
  • Repositioning technologies
  • The resistors to repositioning
    • Most repositioned drugs are old, with little patentprotection
      • Repositioned drugs tend to be protected by method of usepatents
      • Seeking drug approval for marketed drugs
    • Prior safety and toxicology data may be incomplete orinadequate
    • Repositioning a drug for which primary indication use isstill active
    • Acquiring discontinued drugs
• CHAPTER 3 KEY PLAYERS IN DRUG REPOSITIONING
  • Ore Pharmaceuticals - one of the most established playersin drug repositioning
    • Ore Pharmaceuticals' s corporate history
    • Ore Pharmaceuticals' s screening process is a composite ofseveral technology platforms
      • In vivo spatial mapping of drug action and biomarkerchanges
      • Cellular and molecular characterization of drug action
      • In silico approach further validates link between drug anddisease
      • Successful candidates returned to innovator
  • Celentyx - a new player on the repositioning block
    • Novel immune functions for old drugs
    • Celentyx uses cell-based assays to find new indications
  • CombinatoRx - combines old drugs for new indications
    • High-throughput combinatorial methodology
    • CombinatoRx' s early-stage pipeline
      • CRx-102 ready for Phase III development
      • CombinatoRx receives method of use patent for psoriasisdrug
  • Melior - systemizing serendipity
    • High-throughput in vivo drug screening
    • Melior has three early-stage pipeline drugs
    • Melior has formed collaborations with several Big Pharmaplayers
  • Sosei - a pioneer drug repositioning company
    • Sosei' s corporate history
    • Sosei grows its pipeline through partnership
  • KineMed - pathways to repositioning
    • KineMed' s proprietary technology to assess drug-inducedsignal transduction flux
    • Pipeline growth through collaboration
  • Dynogen - a company with a narrow therapeutic focus
    • Pipeline of drugs with a gastrointestinal or genitourinaryfocus
    • Dynogen' s partnerships and collaborations
  • Other repositioning companies
    • Synosia
    • DanioLabs
    • Pharnext
    • Arachnova
• CHAPTER 4 DRUG REPOSITIONING CASE STUDIES
  • Drugs repositioned through serendipity
    • Mozobil (plerixafor) - the repositioning of a discontinueddrug
      • Stem cell mobilization for cancer patients
    • Blind screen throws up antibiotics to treat neurologicaldisease
      • Ceftriaxone as the most potent neuroprotector
    • Raloxifene - a marriage of serendipity and informedinsight
      • One drug, two mechanisms of action
  • Drugs repositioned through informed insight
    • Rituximab - rational repositioning for multipleindications
      • Approval for rheumatoid arthritis
      • Off-label use for systemic lupus erythematosus but failurein clinical trials
      • In development for multiple sclerosis
      • The risks of repositioning
    • HIV protease inhibitor to treat cancer
      • Viracept (nelfinavir) most promising of the proteaseinhibitors
    • Maraviroc
    • Etanercept - from inflammation to neurodegeneration
  • Repositioning which does not fall neatly into either class
    • Rapamycin, antifungal, immunosuppressant and cancertreatment
      • Antiangiogenic properties of rapamycin
      • Rapamycin analog Certican (everolimus) in development forcancer
    • Avastin - reverse repositioning
• CHAPTER 5 REPOSITIONING GOING FORWARD
  • Prospect of internal repositioning by innovators
  • Relationship between innovators and repositioners
    • Acquisition of repositioning companies by innovators
    • Repositioning companies fueling their own developmentprocess
  • Competition to acquire drug candidates could lead toconsolidation
  • One drug, too many indications?
  • Emerging approaches - public sector funded small moleculebased screening sectors
  • Optimization of repositioning
  • Combinatorial development the way forward
• CHAPTER 6 BIBLIOGRAPHY
  • Publications and online articles
  • Conference literature
  • Datamonitor resources
• APPENDIX
  • Abbreviations
• List of Tables
  • Table 1: Breakdown of R&D investment for US Pharma,2005
  • Table 2: Ore Pharmaceuticals' s alliance profile, 2005-07
  • Table 3: CombinatoRx' s recent alliances, 2006-07
• List of Figures
  • Figure 1: Ways to reposition drugs
  • Figure 2: Weak pipelines drive adoption of drugrepositioning
  • Figure 3: R&D investment and productivity out ofsynch, 1996-2006
  • Figure 4: Drug repositioning versus de novo drugdevelopment
  • Figure 5: The innovative drug development process
  • Figure 6: Drug repositioning as a means of streamliningthe development process
  • Figure 7: Methods used to identify suitable drugcandidates for repositioning
  • Figure 8: Major issues impacting on the repositioningprocess
  • Figure 9: Summary of some of the major companiesinvolved in repositioning
  • Figure 10: Ore Pharmaceuticals' s multidisciplinary drugtechnology platform
  • Figure 11: Outline of Celentyx' s drug repositioning plan
  • Figure 12: CombinatoRx' s drug development pipeline, 2008
  • Figure 13: Melior' s drug development pipeline, 2008
  • Figure 14: Sosei' s drug development pipeline, 2008
  • Figure 15: KineMed' s metabolic pathway plan, 2008
  • Figure 16: Dynogen' s drug development pipeline, 2008
  • Figure 17: Plerixafor' s action in HIV and stem cellmobilization
  • Figure 18: Antibiotic and neuroprotective actions ofceftriaxone
  • Figure 19: Raloxifene' s action in osteoporosis andbreast cancer
  • Figure 20: Rituximab approved and/in development forseveral indications
  • Figure 21: Protease inhibitor nelfinavir in cancer
  • Figure 22: Maraviroc in HIV and rheumatoid arthritis
  • Figure 23: Etanercept in Alzheimer' s disease
  • Figure 24: Rapamycin pathways in cancer andimmunosuppression
  • Figure 25: Avastin versus Lucentis for age-relatedmacular degeneration
  • Figure 26: Issues impacting drug repositioning in thefuture