Abstract
At any given time, a number of drug targets are attracting considerable
interest from different pharmaceutical companies. The emergence of such
targets as hot topics of research usually becomes apparent before the
introduction of clinical candidates by a rapid increase in the level of
patenting and research activity directed toward them. Metabolic and
Inflammatory Disease R&D: An Assessment of 5 Highly Promising Therapeutic
Classes, by Peter Norman, MBA, PhD, a new report from Insight Pharma Reports,
details targets of high interest that are primarily of relevance to
inflammatory or metabolic diseases and toward which few, if any, compounds
have progressed into Phase II studies.
Such extensive patenting and research focus is no guarantee of commercial
success, as illustrated by the recent examples of lipoxygenase inhibitors and
leukotriene antagonists- with the more intensive activity directed at the
former providing negligible commercial returns while the latter led to 3
successful products. To help deal with such uncertainty, Metabolic and
Inflammatory Disease R&D: An Assessment of 5 Highly Promising Therapeutic
Classes identifies and assesses the potentially successful efforts in each
of 5 different areas:
- Chemokine antagonists
- Toll-like receptors
- Melanin-concentrating hormone antagonists
- Melanocortin MC4 agonists
- 11β-hydroxysteroid dehydrogenase inhibitors
Selection of these 5 compound classes was based on an assessment of the levels
of patenting and R&D activity directed against various targets currently of
considerable interest in creating new agents for the treatment of
inflammatory, autoimmune, or metabolic disorders.
For instance:
- In January 2007, 11 chemokine antagonists from 9 different companies were
in clinical development for the treatment of inflammatory disorders, with 2 of
these drugs being the focus of high-value commercial deals. Many more
chemokine antagonists are either in preclinical development or lead
optimization, and most of the major pharmaceutical companies have current R&D
efforts directed at chemokine receptor targets.
- For the 10 identified toll-like receptors (TLRs), current activity centers
around development of both TLR agonists and antagonists to treat conditions
ranging from sepsis to cancer. Metabolic and Inflammatory Disease R&D: An
Assessment of 5 Highly Promising Therapeutic Classes provides a thorough
analysis of these TLR potentials, plus succinct charts of Strengths,
Weaknesses, Opportunities, and Threats for these and other products in
development.
Each of the 5 target classes considered in this report has the potential to
provide high-revenue drugs, for the treatment of inflammatory disease,
obesity, and metabolic syndrome. Details are provided for the following
diseases:
Inflammatory Diseases
- Respiratory diseases
- Arthritis
Metabolic Diseases
- Diabetes
- Obesity
- Metabolic Syndrome
- Lipid Disorders
Metabolic and Inflammatory Disease R&D: An Assessment of 5 Highly Promising
Therapeutic Classes details and assesses the efforts of more than 20 major
pharmaceutical companies and more than 25 additional companies to manage the
development of potential metabolic/inflammatory therapeutic products through
R&D into the clinic. Leading researchers at companies at the forefront of R&D
in these target areas offer their views of the challenges, the applications,
and the relevant clinical data that will determine their potential use in
medicine.
This report is an essential tool for individuals involved in the research,
development, licensing, and portfolio management of potential therapeutics for
metabolic and inflammatory diseases.
Table of Contents
Chapter 1
- INTRODUCTION
- 1.1 Target-Based Approaches to Drug Discovery
- 1.2 Identification of Current High-Profile Targeted Approaches
- Inflammatory and Immune Diseases
- Metabolic Diseases
- 1.3 Does Extensive Activity Predict Success?
- Success from High Activity
- Leukotriene CysLT1 Receptor Antagonists
- PDE5 Inhibitors
- COX-2 Inhibitors
- Failures Despite Intense Efforts
- 5-Lipoxygenase Inhibitors
- Renin Inhibitors
- Thromboxane Antagonists
- Long-lived Efforts
- p38 MAP Kinase
- PDE4 Inhibitors
- 1.4 Reasons for Failures
Chapter 2
- METHODOLOGY: IDENTIFYING HIGH-PROFILE AREAS OF EFFORT
- 2.1. Medical Advances
- 2.2. Literature Activity
- 2.3. Meetings
- 2.4. Patenting Activity
- 2.5. Commercial Deals
Chapter 3
- HIGH-PROFILE TOPICS IN INFLAMMATORY AND METABOLIC DISEASES
- 3.1. Inflammatory Diseases
- Respiratory Diseases
- Arthritis
- 3.2. Metabolic Diseases
- Diabetes
- Obesity
- Metabolic Syndrome
- Lipid Disorders
Chapter 4
- CHEMOKINE ANTAGONISTS
- 4.1. Chemokines
- 4.2. Targets
- CCR Receptors
- CXCR Receptors
- 4.3. Pathophysiological Role(s)
- Inflammatory Processes
- HIV Infection
- 4.4. Potential Therapeutic Indications
- Atherosclerosis
- Allergic Rhinitis
- Asthma
- Chronic Obstructive Pulmonary Disease
- Multiple Sclerosis
- Rheumatoid Arthritis
- Cancer
- 4.5. Possible Pitfalls
- CCR Receptors
- CXCR Receptors
- CCR1 Antagonists
- SH-T-04268-H
- CCR2 Antagonists
- Chemokine Antagonists: Strong Evidence ... Well Validated. Q&A with Dr.
Kris Vaddi, vice president, Preclinical Biology, Incyte, and Dr. Robert
Newton, Drug Discovery Biology, Incyte
- CCR3 Antagonists
- CCX-282
- CXCR2 Antagonists
- SCH-527123
- GSK-656933
- DF-1681
- CTCE-9908
- Preclinical Efforts
- 4.6. Active Major Companies
- Amgen
- Astellas
- AstraZeneca
- Bayer Schering
- Boehringer Ingelheim
- Bristol-Meyers Squibb
- Daiichi Sankyo
- GlaxoSmithKline
- Hoffmann-La Roche
- Janssen
- Merck
- Novartis
- Pfizer
- sanofi-aventis
- Schering-Plough
- Takeda
- Wyeth
- 4.7. Other Active Companies
- AnorMED
- ChemoCentryx
- Chemokine Therapeutics
- Dompe
- Incyte
- Millennium Pharmaceuticals
- Ono Pharmaceutical
- Pharmacopeia Drug Discovery
- UCB SA
- 4.8. Significant Commercial Deals
- 4.9. Current Outlook
Chapter 5
- TOLL-LIKE RECEPTOR MODULATORS
- 5.1. Pathophysiological Role(s)
- 5.2. Potential Therapeutic Indications
- 5.3. Possible Pitfalls
- 5.4. Level of Activity, 2000 to 2006
- 5.5. Development Compounds
- TLR-3 Agonists
- Ampligen
- TLR-4 Modulators
- Eritoran
- TAK-242
- CRX-675
- TLR-7 Agonists
- 852A
- Isatoribine and ANA-975
- ANA-773
- Toll-like Receptors: Opportunities in Numerous Disease States. Q&A with
Professor Luke O' Neill, Opsana Therapeutics
- TLR-9 Agonists
- PF-3512676
- Tolamba, Heplisav, and ISS-1018
- CpG-10101
- IMO-2055
- Preclinical Agents
- 5.6. Active Major Companies
- AstraZeneca
- Eisai
- GlaxoSmithKline
- Novartis
- Pfizer
- sanofi-aventis
- Takeda
- 5.7. Other Active Companies
- 3M Pharmaceuticals
- Anadys
- Coley Pharmaceuticals
- Dynavax Technologies
- Hemispherx Biopharma
- Idera Pharmaceuticals
- Innate Pharma
- Opsona Therapeutics
- 5.8. Significant Commercial Deals
- 5.9. Current Outlook
Chapter 6
- 11β-HYDROXYSTEROID DEHYDROGENASE INHIBITORS
- 6.1. 11β-Hydroxysteroid Dehydrogenase
- 6.2. Pathophysiological Role(s)
- 6.3. Potential Therapeutic Indications
- Type 2 Diabetes
- 11β-HSD Inhibitors: Broad Applications in Metabolic Disease. Q&A
with Dr. Greg Hollis, vice president, Advanced Technology, Incyte; Dr.
Deborah Hunter, leader, Incyte; and Dr. Nigel Vicker, group leader,
Discovery Chemistry, Ipsen
- Metabolic Syndrome
- Obesity
- Memory Disorders
- Inflammation
- 6.4. Possible Pitfalls
- INCB-13739
- AMG-221
- Preclinical Efforts
- 6.5. Active Major Companies
- Abbott
- Amgen
- AstraZeneca
- Hoffman-La Roche
- Janssen
- Merck
- Pfizer
- Takeda
- Wyeth
- 6.6. Other Active Companies
- Bionetworks GmbH
- Biovitrum AB
- Evotec AG
- Incyte
- Sterix
- 6.7. Significant Commercial Deals
- 6.8. Current Outlook
Chapter 7
- MELANOCORTIN RECEPTOR MODULATORS
- 7.1. Melanocortin Receptors
- 7.2. Drug Targets
- 7.3. Pathophysiological Role(s)
- 7.4. Potential Therapeutic Indications
- Obesity
- Sexual Dysfunction
- Depression and Anxiety
- 7.5. Possible Pitfalls
- Bremelanotide
- AP-214
- Preclinical Efforts
- MC4 Agonists
- MC4 Antagonists
- 7.6. Active Major Companies
- Eli Lilly
- Merck
- Novartis
- Novo Nordisk
- Roche
- 7.7. Other Active Companies
- Action Pharma
- Ipsen
- Millennium Pharmaceuticals
- Neurocrine Biosciences
- Palatin Technologies
- Procter & Gamble
- Santhera
- Taisho
- 7.8. Significant Commercial Deals
- 7.9. Commercial Outlook
Chapter 8
- MELANIN-CONCENTRATING HORMONE RECEPTOR ANTAGONISTS
- 8.1. Melanin-Concentrating Hormone
- 8.2. MCH-1 Receptor
- 8.3. Pathophysiological Role(s)
- 8.4. Potential Therapeutic Indications
- Obesity
- Depression and Anxiety
- 8.5. Possible Pitfalls
- 8.6. Development Compounds
- 8.7. Clinical Compounds
- AMG-076
- 856464
- NGD-4715
- Preclinical Efforts
- 8.8. Active Major Companies
- Abbott Laboratories
- Amgen
- AstraZeneca
- Boehringer Ingelheim
- Eli Lilly
- GlaxoSmithKline
- Merck
- sanofi-aventis
- Schering-Plough
- Takeda
- 8.9. Other Active Companies
- 7TM Pharma A/S
- Arena Pharmaceuticals
- Biovitrum
- Lundbeck
- Neurocrine Biosciences
- Neurogen
- Procter & Gamble
- Taisho Pharmaceuticals
- 8.10. Significant Commercial Deals
- 8.11. Current Outlook
References
Glossary of Selected Terms
Company Index with Web Addresses
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