Abstract
The pharmaceutical industry is exhaustively exploring novel targets in the search for new drugs to treat inflammatory diseases. Delving in-depth into these efforts, this report provides:
- An analysis of six diseases: rheumatoid arthritis, inflammatory bowel disease, psoriasis, lupus, multiple sclerosis, and asthma
- An assessment of existing drug therapies for these diseases
- Discussion of pharmacological R&D strategies being employed by the industry in developing both biological and small-molecule agents for these diseases
- Review of the approximately 200 compounds in clinical development and assessment of particularly noteworthy drug candidates for these diseases
- Autoimmune disorders and asthma have drawn a great deal of attention from the pharmaceutical industry. The most successful new approach to treating inflammatory diseases in the last decade has addressed the pro-inflammatory role of cytokines, notably TNF-alpha, in these types of conditions. Three TNF-alpha blockers-Enbrel (etanercept), Remicade (infliximab), and Humira (adalimumab)-are now marketed for treating a range of autoimmune diseases, and they enjoy true blockbuster status, with aggregate sales topping $9 billion in 2006.
Nevertheless, the door remains open for improved therapeutics. Some patients do not respond to the TNF-alpha inhibitors; the effectiveness of the agents depends on long-term, even lifelong, administration; and they have been linked to tuberculosis, lymphoma, and other adverse effects.
Several new biological agents have begun to carve their own niches in the massive edifice of the TNF-alpha blockers. Orencia (abatacept), a T-cell co-stimulation modulator, was approved for the treatment of rheumatoid arthritis in 2005; Rituxan (rituximab), an anti-CD20 antibody, for rheumatoid arthritis in 2006; and Tysabri (natalizumab), an adhesion molecule blocker, for multiple sclerosis in 2006 and Crohn' s disease in 2008.
A recurrent theme in discussions of treatment options for autoimmune diseases is the inadequacy of the standard of care. Management and pharmacotherapy are seeing only incremental improvements. Patients with asthma, an allergic disease, tend to fare well with the drugs currently available, though better treatment options with less potential for side effects are needed.
The complexity of the immune system provides both opportunity and challenge for the pharmaceutical industry. There is a seemingly endless list of cytokines, receptors, and enzymes that can be disrupted in patients with autoimmune and inflammatory diseases, and the sheer number of options leaves plenty of chances for companies-large established players and specialized newcomers alike-to carve out niches. On the other hand, the transition from brainstorm to marketed drug is fraught with pitfalls. Targeting a single receptor or protein often means being foiled by the immune system' s redundancy, while cutting too wide a swath through the system can result in unexpected side effects.
Table of Contents
Chapter 1 INTRODUCTION: THE IMMUNE SYSTEM AND THE INFLAMMATORY RESPONSE
- 1.1. The Immune System
- 1.2. Immune Dysfunction and Autoimmune Disease
Chapter 2 REVIEW OF THE INFLAMMATORY DISEASES: EPIDEMIOLOGY, PATHOLOGY, DIAGNOSIS, AND SYMPTOMS
- 2.1. Rheumatoid Arthritis
- Pathology
- Causes
- Diagnosis
- Epidemiology
- 2.2. Inflammatory Bowel Disease
- Pathology
- Causes
- Diagnosis
- Epidemiology
- 2.3. Psoriasis
- Pathology
- Causes
- Diagnosis
- Epidemiology
- 2.4. Lupus
- Pathology
- Causes
- Diagnosis
- Epidemiology
- 2.5. Multiple Sclerosis
- Pathology
- Causes
- Diagnosis
- Epidemiology
- 2.6. Asthma
- Pathology
- Causes
- Diagnosis
- Epidemiology
Chapter 3 CURRENT PHARMACOLOGICAL TREATMENT OPTIONS
- 3.1. Rheumatoid Arthritis
- Analgesics and NSAIDS
- Corticosteroids
- Synthetic DMARDs
- Methotrexate
- Arava (Leflunomide)
- Other DMARDs
- Biological DMARDs
- Enbrel (Etanercept)
- Remicade (Infliximab)
- Humira (Adalimumab)
- Kineret (Anakinra)
- Orencia (Abatacept)
- Rituxan (Rituximab)
- 3.2. Inflammatory Bowel Disease
- Aminosalicylates
- Corticosteroids
- Immunomodulators
- Azathioprine, 6-Mercaptopurine, and 6-Thioguanine
- Methotrexate
- Cyclosporine
- Remicade (Infliximab)
- Humira (Adalimumab)
- Tysabri (Natalizumab)
- Antibiotics
- 3.3. Psoriasis
- Topical Therapies
- Corticosteroids
- Vitamin D3 and A Compounds
- Retinoids
- Coal Tar
- Anthralin
- Salicylic Acid
- Light Therapy
- Systemic Therapy
- Methotrexate
- Cyclosporine
- Oral Retinoids
- Hydroxyurea
- Amevive (Alefacept)
- Raptiva (Efalizumab)
- Enbrel (Etanercept)
- Remicade (Infliximab)
- Humira (Adalimumab)
- Topical Therapies
- 3.4. Lupus
- NSAIDs
- Antimalarials
- Corticosteroids
- Immunomodulators
- 3.5. Multiple Sclerosis
- Corticosteroids
- Disease-Modifying Agents
- Interferon Beta
- Copaxone (Glatiramer Acetate)
- Novantrone (Mitoxantrone)
- Tysabri (Natalizumab)
- Other Immunomodulators
- 3.6. Asthma
- Quick-Relief Medications
- Bronchodilators
- Oral Corticosteroids
- Long-Term Control Medications
- Inhaled Corticosteroids
- Bronchodilators
- Mast Cell Stabilizers
- Leukotriene Modifiers
- Xolair (Omalizumab)
- Quick-Relief Medications
Chapter 4 COMPOUNDS IN DEVELOPMENT: THE NEXT GENERATION OF DRUGS FOR INFLAMMATORY DISEASES
- 4.1. New Approaches to Inflammatory Diseases
- Tumor Necrosis Factor Family Inhibitors
- Interleukin Inhibitors
- Other Cytokine Inhibitors
- Chemokine Receptor Antagonists
- Anti-inflammatory Cytokines
- Compounds Targeting T-Cell Antigens
- Compounds Targeting B-Cell Antigens
- Complement Inhibitors
- Adhesion Molecule Blockers
- Protease Inhibitors
- TACE
- ICE
- Cathepsin S
- Kinase Inhibitors
- p38 MAP Kinase
- JNK
- NF-κB
- Other Kinases
- 4.2. Setbacks
- 4.3. Rheumatoid Arthritis
- TNF-alpha Inhibitors
- UCB
- Centocor
- Targeted Genetics
- Arana Therapeutics
- Xencor
- Meyer Pharmaceuticals
- Pharmaxis
- Ception Therapeutics
- Ablynx
- Nastech Pharmaceutical
- Devgen
- Interleukin Inhibitors
- Amgen
- Kinase Inhibitors
- Rigel Pharmaceuticals
- Plexxikon
- TNF-alpha Inhibitors
- 4.4. Inflammatory Bowel Disease
- Adhesion Molecule Blockers
- Atlantic Healthcare
- Millennium Pharmaceuticals
- Other Compounds
- InDex Pharmaceuticals
- Genzyme
- Adhesion Molecule Blockers
- 4.5. Psoriasis
- TNF Inhibitors
- Apollo Life Sciences
- York Pharma
- Interleukin Inhibitors
- Centocor
- Abbott Laboratories
- Calcineurin Inhibitors
- Isotechnika
- Biogen Idec
- CombinatoRx
- Celgene
- Vitamin D Analogs
- CollaGenex Pharmaceuticals
- Cytochroma
- TNF Inhibitors
- 4.6. Lupus
- Immunomodulators
- La Jolla Pharmaceutical
- Genelabs Technologies
- BLyS Inhibitors
- Human Genome Sciences
- ZymoGenetics
- Anthera Pharmaceuticals
- Biogen Idec/Genentech
- Xencor
- Toll-like Receptor Antagonists
- Coley Pharmaceutical Group
- Dynavax Technologies
- Idera Pharmaceuticals
- Immunomodulators
- 4.7. Multiple Sclerosis
- Immunomodulators
- Biogen Idec
- Genzyme/Bayer Schering Pharma
- Novartis
- Cytokines
- Nastech Pharmaceutical
- Syntonix Pharmaceuticals
- Ichor Medical Systems
- Nautilus Biotech
- Flamel Technologies
- Modigene
- Bolder BioTechnology
- CoGenesys
- Allozyne
- Peptide Vaccines and MBP-Base Therapeutics
- Orchestra Therapeutics
- BioMS Medical/Eli Lilly
- Bayhill Therapeutics
- Remyelinating Agents
- Biogen Idec
- Acorda Therapeutics
- Immunomodulators
- 4.8. Asthma
- Interleukin Inhibitors
- GlaxoSmithKline
- MedImmune/BioWa
- Aerovance
- Amgen
- Genentech
- Altair Therapeutics
- CSL/Merck
- Synairgen
- Phosphodiesterase-4 Inhibitors
- Nycomed
- Glenmark Pharmaceuticals/Forest Laboratories
- MediciNova
- Other PDE4 Inhibitors
- Toll-like Receptor Agonists
- Coley Pharmaceutical Group/Sanofi-Aventis
- Dynavax Technologies
- Idera Pharmaceuticals
- InDex Pharmaceuticals
- CRTH2 Antagonists
- Interleukin Inhibitors
