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
- 11β-HSD1
- 11β-HSD2
- 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
