臨床開発に入るキナーゼ阻害剤の数は近年大幅に増加しています。大手製薬会社に加え新規参入企業が開発に着手しています。2020年までに小分子キナーゼ阻害剤は250億米ドルを超える年間収益を生み出すものとみられています。
当レポートでは、キナーゼを標的とした研究開発動向、現在のキナーゼ阻害剤パイプライン、現在までの商業的成果、短期的、長期的市場見通し、同分野に参入する企業の活動についてまとめ、概略下記の構成でお届けいたします。
Abstract
The number of kinase inhibitors entering clinical development has increased
significantly in recent years. In addition to major pharmaceutical and biotech
companies, an increasing number of emerging companies are focusing on their
development. By 2020, small-molecule kinase inhibitors could generate annual
revenues > $25 billion.
This report assesses:
- R&D considerations specific to targeting kinases
- Current kinase inhibitor pipelines
- Commercial successes to date
- Near- and longer-term market outlook
- Corporate activities of firms involved with kinases
Kinases are now firmly established as a major class of drug targets. It was
previously thought that kinases would be intractable drug targets due to the
presumed need to compete with ATP and the assumption that sufficient
selectivity would be unattainable. However, considerable progress has been
made in understanding kinases and their function, and the past few years have
seen a number of kinase inhibitors reach the market. Imatinib (Novartis'
Gleevec) is currently the most commercially successful, with sales reaching
$3.7 billion in 2008. Erlotinib (OSI/Roche' s Tarceva) generated revenues of
$1.1 billion the same year.
In recent years, there has been an explosion in the number of kinase
inhibitors entering the clinic, and many more are in preclinical development.
Kinase Therapeutics: Pipeline Assessment and Commercial Prospects
identifies which kinase families and their respective members have
attracted the greatest interest for therapeutic development and in which
indications these kinases play a physiological or pathophysiological role and
thus are most relevant for kinase inhibitor development.
This report extensively reviews small-molecule kinase inhibitors identified as
being in active clinical development. Oncology indications accounted for 79%
of these inhibitors, while inflammatory indications accounted for nearly half
of the kinase inhibitors not being developed to treat cancers. Kinase
inhibitors identified as being in clinical development are analyzed by
clinical phase (Phases I-III) and by target.
Kinase Therapeutics: Pipeline Assessment and Commercial Prospects
examines the considerable discrepancies in the levels of activities amongst
major companies regarding kinase inhibitor development. The perceived
tractability of kinases as drug targets has led to an increasing number of
emerging companies focused on kinase inhibitor development. Many are
developing kinase inhibitors in partnership with major companies, while others
may be potential acquisition targets. Further, the desire to extensively
profile kinase inhibitors has led to the emergence of companies that offer
such services. The activities of selected specialist and service companies are
also examined.
The period to 2015 should see a number of additional kinase inhibitors reach
the market. As a result, annual revenues generated by kinase inhibitors should
approximately double by 2015 from the near $8 billion generated in 2008. The
large number of kinase inhibitors currently in Phase II should ensure that the
period between 2015 and 2020 sees a steady flow of new kinase inhibitors
approved for use, ensuring continued growth of their commercial revenues.
About the Author
Peter Norman, PhD, MBA is a pharmaceutical consultant and analyst based
in Burnham Beeches, near Windsor, England. He has written and presented widely
on various aspects of respiratory disease, drug development, and on the
analysis of diverse therapeutic markets. Dr. Norman has over 20 years of
experience of the pharmaceutical industry in both R&D and competitive
intelligence. His publications include many reviews and 16 original scientific
papers and 11 patents, together with a number of management reports. The
latter have been published by a number of companies including FT
Pharmaceuticals, Urch Publications, SMI and Decision Resources, Informa, and
Insight Pharma Reports (a division of Cambridge Healthtech Institute). Dr.
Norman holds science degrees from Cambridge University and Brunel University
and an MBA degree from the Open University.
Table of Contents
CHAPTER - 1
KINASES
- 1.1. The Function of Kinases
- 1.2. The Human Kinome
- 1.3. Kinase Classification
- AGC Family
- CAMK Family
- CMGC Family
- CK1 Family
- STE Family
- TK Family
- TKL Family
- Atypical Protein Kinases
- 1.4. Kinase Structure
- 1.5. Kinases as Drug Targets
CHAPTER - 2
INDICATIONS
- 2.1. Introduction
- 2.2. Cancer
- 2.3. Angiogenic Conditions
- 2.4. Inflammatory Diseases
- 2.5. Metabolic Disorders
- 2.6. CNS Conditions
- 2.7. Cardiovascular Disease
CHAPTER - 3
R&D CONSIDERATIONS
- 3.1. Introduction
- 3.2. Kinase Selectivity
- Profiling
- Selectivity Profiles of Selected Inhibitors
- How Selective?
- 3.3. Structural Features
- X-Ray Structures and Multiple Conformations
- 3.4. Kinase Mutations
- 3.5. Intellectual Property Issues
CHAPTER - 4
CURRENT COMMERCIAL SUCCESSES
- 4.1. Introduction
- 4.2. Small Molecules
- Overview
- Abl Inhibitors
- Gleevec (imatinib)
- Tasigna (nilotinib) and Sprycel (dasatinib)
- EGF Family Inhibitors
- Tarceva (erlotinib) and Iressa (gefitinib)
- Tykerb (lapatinib)
- Multi-Kinase Inhibitors
- Nexavar (sorafenib)
- Sutent (sunitinib)
- Palladia (toceranib) and Masivet (mastinib)
- mTOR Inhibitors
- Rapamune (sirolimus)
- Torisel (temsirolimus), Afinitor/Certican (everolimus), Endeavor
(zotarolimus)
- Rho Inhibitor
- 4.3. Biological Agents
CHAPTER - 5
CURRENT KINASE INHIBITOR PIPELINES
- 5.1. Introduction
- 5.2. Overview
- 5.3. Kinase Inhibitors in Phase III
- Enzastaurin and Ruboxistaurin
- Midostaurin
- Pan-VEGFR Inhibitors
- Votrient (pazopanib)
- Cediranib
- Motesanib
- Axitinib
- Aflibercept
- Vandetanib
- BIBW-2992
- Neratinib
- Pertuzumab
- FGFR Inhibitors
- Alvocidib
- Bosutinib
- Lestaurtinib
- Ridaforolimus
- Masitinib
- BMS-907351
- CP-690550
- INCB-18424
- 5.4. Kinase Inhibitors in Phase II Development
- 5.5. Kinase Inhibitors in Phase I Development
- 5.6. Growth Factor Receptor Kinases
- ErbB Family Kinases
- ErbB2 and ErbB3
- ErbB2 and EGFR
- Pan-ErbB
- Antibodies
- FGF
- IGF
- VEGF
- Multi-Kinase Inhibitors
- Flt3
- 5.7. Popular Kinase Cascades
- PI3K, Akt, mTOR, S6K
- Perifosine
- Triciribine
- Archexin
- Ras, Raf, MEK, ERK
- Roche
- Ardea Biosciences and Bayer
- Array and AstraZeneca
- JAK Family
- 5.8. Cell Cycle Inhibitors
- Cyclic-Dependent Kinase (CDK)
- Checkpoint Kinase (Chk)
- Polo-Like Kinase (PLK)
- 5.9. Popular Kinase Targets
- Abl
- p38
- GSK-3
- Protein Kinase C
- Aurora
- Broad Spectrum
- Pan-Aurora
- Aurora 1
- Aurora 2
- c-Met
- Rho
- JNK
- Src Family
- Kinases in Inflammatory Diseases
- 5.10. Other Kinases
- Serine/Threonine Kinases
- Tyrosine Kinases
- Tyrosine-Like, CAMK, and Atypical Kinases
- 5.11. Outlook
CHAPTER - 6
CORPORATE ACTIVITIES
- 6.1. Introduction
- 6.2. Major Companies
- Abbott
- Amgen
- Astellas
- AstraZeneca
- Bayer
- Boehringer Ingelheim
- Bristol-Myers Squibb
- Daiichi Sankyo
- Eisai
- Eli Lilly
- GlaxoSmithKline
- Johnson & Johnson
- Merck & Co.
- Merck Serono
- Novartis
- Pfizer
- Roche
- sanofi-aventis
- Takeda
- 6.3. Specialist Companies
- ACT Biotech
- Advenchen
- Array BioPharma
- Avila Therapeutics
- Calistoga Pharmaceuticals
- Cellzome
- Cyclacel Pharmaceuticals
- Cylene Pharmaceuticals
- Deciphera Pharmaceuticals
- Emiliem
- Exelixis
- Intellikine
- Kai Pharmaceuticals
- Nerviano Medical Sciences
- Oncalis
- OSI Pharmaceuticals
- Rigel Pharmaceuticals
- S*Bio
- Semafore Pharmaceuticals
- SuperGen
- TargeGen
- Vertex Pharmaceuticals
- 6.4. Service Companies
- Ambit Biosciences
- Galapagos
- Invitrogen
- KINAXO Biotechnologies
- ProQinase
- SignalChem
- Upstate (Millipore)
CHAPTER - 7
MARKET OUTLOOK
- 7.1. Introduction
- 7.2. Near-Term Developments
- 7.3. Longer-Term Outlook
CHAPTER - 8
EXPERT INTERVIEWS
REFERENCES
COMPANY INDEX WITH WEB ADDRESSES
