Treating Autoimmune Diseases: The market potential for new therapeutic options
Therapeutic
This report contains in-depth coverage of:
A better understanding of autoimmune diseases has led to opportunities for therapies to treat the underlying causes, rather than just manage the symptoms of these diseases. Scrip's Treating Autoimmune Diseases: The market potential for new therapeutic options is an invaluable report incorporating a comprehensive guide to how new technologies are being embraced to provide new therapeutic solutions, answering your questions:
The report also includes detailed profiles of 17 leading companies, studying their pipeline therapies for autoimmune diseases, as well as covering drugs in development from many other companies.
Published: June 2001
Pages: 243
Ref: BS1132E
Price: £495/$1,040/¥119,000
For further information about this report, please contact our Customer Helpdesk on:
Tel: +44 (0)20 8332 8965 / 66
Fax: +44 (0)20 8332 8992
E-mail: [email protected]
CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY
LIST OF ABBREVIATIONS AND GLOSSARY
CHAPTER 1 INTRODUCTION TO AUTOIMMUNE DISEASES
1.1 Autoimmune diseases
1.2 The immune system
1.2.1 The innate immune system
1.2.1.1 Cellular components
1.2.1.2 The complement system
1.2.2 The adaptive immune system
1.2.2.1 T cells
1.2.2.2 B cells
1.2.2.3 Natural killer cells
1.3 Immune recognition and cellular function
1.4 The inflammatory cascade
1.4.1 Inflammatory mediators
1.4.1.1 Cytokines
1.4.1.2 Products of arachidonic acid metabolism
1.5 Breakdown of tolerance and autoimmune disease
1.5.1 HLA class II molecules
1.5.2 T cell dysfunction
1.6 Autoantibodies and autoimmune disease
1.7 Aim of the report
CHAPTER 2 SPECIFIC AUTOIMMUNE DISEASES
2.1 Multiple sclerosis
2.1.1 Epidemiology
2.1.2 Aetiology
2.1.3 Pathogenesis
2.1.4 Clinical features
2.1.5 Diagnosis
2.1.6 Management
2.1.6.1 Acute treatment of relapses
2.1.6.2 Symptomatic treatments
2.1.6.3 Disease-modifying treatments
2.1.7 National Institute for Clinical Excellence and the National Health Service
2.2 Rheumatoid arthritis
2.2.1 Epidemiology
2.2.2 Aetiology
2.2.3 Pathogenesis
2.2.4 Clinical features
2.2.5 Diagnosis
2.2.6 Stages in the development of rheumatoid arthritis
2.2.7 Articular disease
2.2.8 Extra-articular disease
2.2.9 Management
2.3 Systemic lupus erythematosus
2.3.1 Epidemiology
2.3.2 Aetiology
2.3.3 Pathogenesis
2.3.4 Pathology
2.3.5 Clinical features
2.3.6 Lupus variants
2.3.7 Diagnosis
2.3.8 Management
2.3.9 Antiphospholipid syndrome
2.4 Psoriasis
2.4.1 Aetiology
2.4.2 Pathogenesis
2.4.3 Clinical features
2.4.4 Management
2.4.5 Psoriatic arthritis
2.5 Inflammatory bowel disease
2.5.1 Types of inflammatory bowel disease
2.5.1.1 Crohn's disease
2.5.1.2 Ulcerative colitis
2.5.2 Epidemiology
2.5.3 Aetiology
2.5.4 Pathogenesis
2.5.5 Diagnosis
2.5.6 Management
2.5.6.1 Non-pharmacological management
2.5.6.2 Pharmacological management
2.5.7 Course and prognosis
2.6 Other autoimmune diseases
2.6.1 Sjögren's syndrome
2.6.1.1 Management
2.6.2 Systemic sclerosis (scleroderma)
2.6.2.1 Management
2.6.3 Autoimmune endocrine diseases
2.6.3.1 Type 1 diabetes
2.6.3.2 Autoimmune thyroid diseases
2.6.4 Autoimmune hepatitis
2.6.5 Myasthenia gravis
2.6.5.1 Management
CHAPTER 3 MARKETED THERAPEUTICS FOR THE MANAGEMENT OF AUTOIMMUNE DISEASES
3.1 Drugs marketed for multiple sclerosis
3.1.1 Interferon-ß1a
3.1.1.1 Recent clinical trials with Avonex
3.1.1.2 Clinical trials with Rebif
3.1.2 Interferon-ß1b
3.1.2.1 Clinical trials
3.1.3 Glatiramer acetate
3.1.3.1 Clinical trials
3.1.4 Mitoxantrone
3.2 Established and recently approved therapies for rheumatoid arthritis
3.2.1 Non-steroidal anti-inflammatory drugs
3.2.1.1 Established non-steroidal anti-inflammatory drugs
3.2.1.2 COX-2 inhibitors
3.2.2 Disease-modifying antirheumatic drugs
3.2.2.1 Methotrexate
3.2.2.2 Sulphasalazine
3.2.2.3 Cyclosporin A
3.2.2.4 Antimalarials
3.2.2.5 D-penicillamine
3.2.2.6 Gold
3.2.2.7 Leflunomide
3.2.2.8 Combination therapy
3.2.3 Corticosteroids
3.2.4 TNF-alpha antagonists
3.2.4.1 Etanercept
3.2.4.2 Infliximab
3.2.4.3 Limitations of anti-tumour necrosis factor-alpha drugs
3.3 Drugs marketed for systemic lupus erythematosus
3.4 Drugs marketed for psoriasis
3.5 Drugs marketed for inflammatory bowel disease
3.5.1 Aminosalicylates
3.5.1.1 Mesalazine
3.5.1.2 Balsalazide
3.5.1.3 Olsalazine
3.5.1.4 Sulphasalazine
3.5.1.5 4-aminosalicylic acid
3.5.2 Corticosteroids
3.5.2.1 Beclomethasone
3.5.2.2 Budesonide
3.5.3 Immunomodulators
3.5.3.1 Methotrexate
3.5.4 Biotherapies
3.5.4.1 Infliximab
CHAPTER 4 PRODUCTS IN RESEARCH AND DEVELOPMENT FOR AUTOIMMUNE DISEASES
4.1 Drugs in development for multiple sclerosis
4.1.1 Fampridine-SR
4.1.2 Cladribine
4.1.3 Micellar paclitaxel
4.1.4 Natalizumab
4.1.5 Anti-IFN
4.1.6 AnergiX.RA
4.1.7 Cannabinoids
4.1.8 Glutamate antagonists
4.2 Drugs in development for rheumatoid arthritis
4.2.1 COX-inhibitors
4.2.2 Anti-tumour necrosis factor-alpha therapy
4.2.3 Monoclonal antibodies
4.2.4 MAP kinase inhibitors
4.2.5 Neurins
4.2.6 Chronotherapeutic products
4.2.7 Glucose-6-phosphate dehydrogenase inhibitors
4.2.8 IL-1 receptor antagonists
4.2.9 AGIX-4207
4.2.10 New disease-modifying antirheumatic drugs
4.3 Drugs in development for the treatment of systemic lupus erythematosus
4.3.1 GL701
4.3.2 LJP 394
4.3.3 5G1.1
4.3.4 Anti-BLyS antibody
4.3.5 IL-10 inhibition as a potential therapy for systemic lupus erythematosus
4.3.6 Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and stem-cell transplantation
4.3.7 New benefits of hydroxychloroquine
4.3.8 New research
4.3.8.1 Cell surface glycan defects
4.3.8.2 CD45 receptors
4.4 Drugs in development for the treatment of psoriasis
4.4.1 Anti-CD11a monoclonal antibody
4.4.2 LFA3TIP
4.4.3 ABX-IL8
4.4.4 IDEC-114
4.4.5 PVAC
4.4.6 Clobetasol
4.4.7 Micellar paclitaxel
4.4.8 Tazarotene cream
4.4.9 IL-20 from ZymoGenetics
4.5 Drugs in development for inflammatory bowel disease
4.5.1 ISIS 2302
4.5.2 Humicade (CDP-571)
4.5.3 LDP-02
4.5.4 BXT-51072
4.5.5 IL-10
4.5.6 IL-11
4.5.7 Thalidomide
4.5.8 Growth hormone studies
4.5.9 P54
4.5.10 Repifermin
4.5.11 CBP-1011
4.5.12 RDP-58
4.5.13 ICM3
CHAPTER 5 THE AUTOIMMUNE THERAPY MARKET
5.1 Market breakdown by disease and population
5.1.1 Prevalence of multiple sclerosis
5.1.2 Prevalence of rheumatoid arthritis
5.1.3 Prevalence of systemic lupus erythematosus
5.1.4 Prevalence of psoriasis
5.1.5 Prevalence and incidence of inflammatory bowel disease
5.1.5.1 Prevalence and incidence of ulcerative colitis
5.1.5.2 Prevalence and incidence of Crohn's disease
5.2 Market shares and values
5.2.1 Multiple sclerosis
5.2.2 Rheumatoid arthritis
5.2.3 Systemic lupus erythematosus
5.2.4 Psoriasis
5.2.5 Inflammatory bowel disease
5.3 The autoimmune diseases market in summary
CHAPTER 6 COMPANY PROFILES
6.1 Abgenix Inc
6.1.1 The company
6.1.2 Financial figures
6.1.3 Products in development for autoimmune diseases
6.2 Aventis Pharma
6.2.1 The company
6.2.2 Agreements
6.2.3 Financial figures
6.2.4 Drugs marketed for autoimmune diseases
6.2.5 Drugs in development for autoimmune diseases
6.3 Biogen Inc
6.3.1 The company
6.3.2 Agreements
6.3.3 Financial figures
6.3.4 Drugs marketed for autoimmune diseases
6.3.5 Drugs in development for autoimmune diseases
6.4 Corixa Corporation
6.4.1 The company
6.4.2 Agreements
6.4.3 Financial figures
6.4.4 Drugs in development for the treatment of autoimmune diseases
6.5 Elan Corporation plc
6.5.1 The company
6.5.2 Agreements
6.5.3 Financial figures
6.5.4 Drugs in development for autoimmune diseases
6.6 Genelabs Technologies Inc
6.6.1 The company
6.6.2 Financial figures
6.6.3 Drugs in development for autoimmune diseases
6.7 Genentech Inc
6.7.1 The company
6.7.2 Agreements
6.7.3 Financial figures
6.7.4 Drugs in development for autoimmune diseases
6.8 Immune Response Corporation
6.8.1 The company
6.8.2 Financial figures
6.8.3 Drugs in development for autoimmune diseases
6.9 Immunex Corporation
6.9.1 The company
6.9.2 Agreements
6.9.3 Financial highlights
6.9.4 Drugs marketed for autoimmune diseases
6.9.5 Development pipeline
6.10 Johnson & Johnson
6.10.1 The company
6.10.2 Financial figures
6.10.3 Drugs marketed for autoimmune diseases
6.10.4 Drugs in development for autoimmune diseases
6.11 La Jolla Pharmaceutical Co
6.11.1 The company
6.11.2 Financial figures
6.11.3 Drugs in development for autoimmune disease
6.12 Millennium Pharmaceuticals Inc
6.12.1 The company
6.12.2 Agreements
6.12.3 Financial figures
6.12.4 Drugs in development for autoimmune diseases
6.13 Pharmacia Corporation
6.13.1 The company
6.13.2 Agreements
6.13.3 Financial highlights
6.13.4 Drugs marketed for autoimmune diseases
6.13.5 Drugs in development for autoimmune diseases
6.14 Schering AG
6.14.1 The company
6.14.2 Agreements
6.14.3 Financial Figures
6.14.4 Drugs marketed for autoimmune diseases
6.14.5 Drugs in development for autoimmune diseases
6.15 Schering-Plough Corporation
6.15.1 The company
6.15.2 Agreements
6.15.3 Financial figures
6.15.4 Drugs marketed for autoimmune diseases
6.15.5 Drugs in development for autoimmune diseases
6.16 Serono SA
6.16.1 The company
6.16.2 Agreements
6.16.3 Financial figures
6.16.4 Drugs marketed for autoimmune diseases
6.16.5 Drugs in development for autoimmune diseases
6.17 Teva Pharmaceutical Industries Ltd
6.17.1 The company
6.17.2 Agreements
6.17.3 Financial highlights
6.17.4 Drugs marketed for autoimmune diseases
LIST OF TABLES
Table 1.1 Examples of autoimmune diseases classified according to the main target organ
Table 1.2 The immunoglobulin classes
Table 2.1 Types of MS and their characteristics
Table 2.2 Licensed indications, dosage schedules, contraindications and other criteria for IFN-ß treatment in RRMS and SPMS
Table 2.3 Clinical features of SLE
Table 2.4 Types of psoriasis
Table 2.5 Symptoms of Crohn's disease
Table 2.6 The principal symptoms of ulcerative colitis
Table 2.7 Sub-classifications of ulcerative colitis
Table 2.8 Drugs used in inflammatory bowel disease
Table 2.9 Examples of current inflammatory bowel disease therapies on the market
Table 2.10 Drugs in clinical development for the treatment of scleroderma
Table 3.1 Established non-steroidal anti-inflammatory drugs
Table 3.2 Disease-modifying antirheumatic drugs used in the treatment of rheumatoid arthritis
Table 3.3 Summary of three multicentre, double-blind randomised trials with leflunomide for the treatment of rheumatoid arthritis
Table 3.4 Drugs launched for the treatment of psoriasis
Table 3.5 Marketed aminosalicylates used in inflammatory bowel disease
Table 4.1 Drugs for multiple sclerosis in clinical development
Table 4.2 Drugs in preclinical development for the treatment of multiple sclerosis
Table 4.3 Drugs in clinical development for the treatment of rheumatoid arthritis
Table 4.4 Drugs in preclinical development for rheumatoid arthritis
Table 4.5 Drugs in development for the treatment of systemic lupus erythematosus
Table 4.6 Drugs in clinical development for the treatment of psoriasis
Table 4.7 Drugs in preclinical development for the treatment of psoriasis
Table 5.1 Prevalence rates for multiple sclerosis in major markets
Table 5.2 Prevalence of multiple sclerosis in the US, forecast to 2020
Table 5.3 Prevalence of rheumatoid arthritis in the US, Japan and the five major European markets, forecast to 2020
Table 5.4 Percentage increase in the prevalence of rheumatoid arthritis in major world markets, 2004-2020
Table 5.5 Prevalence of rheumatoid arthritis in the male population in selected world markets, 1998 projected to 2010
Table 5.6 Prevalence of rheumatoid arthritis in the female population in selected world markets, 1998 projected to 2010
Table 5.7 Prevalence of rheumatoid arthritis in the total population in selected world markets, 2000 projected to 2010
Table 5.8 Prevalence and incidence of systemic lupus erythematosus in the UK, projected to 2020
Table 5.9 Prevalence of systemic lupus erythematosus in the US, forecast to 2020
Table 5.10 Prevalence of systemic lupus erythematosus among the Japanese population based on 1984 data, projected to 2020
Table 5.11 Prevalence of psoriasis the US, Japan and the five major European markets, forecast to 2020
Table 5.12 Percentage change in the prevalence of psoriasis in major world markets, 2004-2020
Table 5.13 Prevalence of ulcerative colitis in the US, Japan and the five major European markets, forecast to 2020
Table 5.14 Percentage change in the prevalence of ulcerative colitis in major world markets, 2004-2020
Table 5.15 Incidence of ulcerative colitis in the US, Japan and the five major European markets, forecast to 2020
Table 5.16 Percentage change in the incidence of ulcerative colitis in major world markets, 2004-2020
Table 5.17 Prevalence of Crohn's disease in the US, Japan and the five major European markets, forecast to 2020
Table 5.18 Percentage change in the prevalence of Crohn's disease in major world markets, 2004-2020
Table 5.19 Incidence of Crohn's disease in the US, Japan and the five major European markets, forecast to 2020
Table 5.20 Sales and forecast sales of drugs for multiple sclerosis, 1998-2002 ($ million)
Table 5.21 Sales of multiple sclerosis drugs by company, 1998�2002 ($ million)
Table 5.22 Sales and forecast sales of Avonex, 1998-2002 ($ million)
Table 5.23 Sales and forecast sales of Betaseron, 1998-2002 ($ million)
Table 5.24 Sales and forecast sales of drugs for rheumatoid arthritis, 1998-2002 ($ million)
Table 5.25 Sales and forecast sales of drugs to treat rheumatoid arthritis, by drug category, 1998�2002
Table 5.26 Sales and forecast sales of drugs to treat arthritis by region, 1998�2002 ($ million)
Table 5.27 Sales of arthritis products by company, 1999-2000
Table 5.28 Drugs in development for the treatment of psoriasis, and market projections
Table 5.29 The market for drugs to treat inflammatory bowel disease, 1998-2002 ($ million)
Table 5.30 The market for drugs to treat inflammatory bowel disease by company, 1998-2002, ($ million)
Table 5.31 Drugs in development for the treatment of inflammatory bowel disease, and market projections
Table 6.1 Abgenix financial figures, 1999�2000 ($ thousand)
Table 6.2 Financial highlights for Aventis SA, 1998-2000 ($ million)
Table 6.3 Pharma sales by business unit, 1999-2000 ($ million)
Table 6.4 Pharma sales by country, 1999-2000 ($ million)
Table 6.5 Drugs marketed by Aventis for autoimmune disease
Table 6.6 Sales of major drugs for autoimmune diseases, 2000 ($ million)
Table 6.7 Drugs in development for autoimmune diseases
Table 6.8 Financial figures, 1996-2000 ($ millions)
Table 6.9 Biogen's product pipeline
Table 6.10 Corixa's financial highlights, 1996-2000 ($ million)
Table 6.11 Corixa's autoimmune disease drug development portfolio
Table 6.12 Financial highlights for Elan corporation, 1998-2000 ($ million)
Table 6.13 Revenues by geographical origin, 1998-1999 ($ million)
Table 6.14 Revenues by class of business ($ million)
Table 6.15 Drugs in development for the treatment of autoimmune diseases
Table 6.16 Genelabs' financial figures, 1996-2000 ($ million)
Table 6.17 Genentech's financial figures, 1996-2000 ($ millions)
Table 6.18 Financial highlights, 1996-2000 ($ million)
Table 6.19 Immune Response's product portfolio for autoimmune diseases
Table 6.20 Selected financial data for Immunex, 1996-2000 ($ million)
Table 6.21 Financial highlights, 1996-2000 ($ million)
Table 6.22 Sales by region, 1996-2000 ($ million)
Table 6.23 Sales by business segment ($ million)
Table 6.24 Financial figures, 1996-2000 ($ million)
Table 6.25 Drugs in development for the treatment of autoimmune diseases
Table 6.26 Financial highlights, 1996-2000 ($ thousand)
Table 6.27 Pharmacia's financial highlights, 1999-2000 ($ million)
Table 6.28 Pharmacia's geographical distribution of total net sales, 2000 ($ million)
Table 6.29 Drugs marketed for autoimmune diseases
Table 6.30 Drugs in development for the treatment of autoimmune diseases
Table 6.31 Financial highlights, 1996-2000 ($ million)
Table 6.32 Sales by region, 1999-2000 ($ million)
Table 6.33 Sales by business area, 1999-2000 ($million)
Table 6.34 Sales of therapeutics, 2000 ($ million)
Table 6.35 Financial highlights, 1996�2000 ($ million)
Table 6.36 Sales by business segment, 1996-2000 ($ million)
Table 6.37 Sales by pharmaceutical category, 1999-2000 ($ million)
Table 6.38 Products in development for autoimmune diseases
Table 6.39 Financial figures, 1996-2000 ($ million)
Table 6.40 Sales by area, 1999-2000 ($ million)
Table 6.41 Sales by therapeutic category ($ million)
Table 6.42 Leading product sales, 1999-2000 ($ million)
Table 6.43 Financial highlights, 1996-2000 ($ million)
LIST OF FIGURES
Figure 2.1 A healthy joint (A) and one showing the characteristic changes observed in rheumatoid arthritis (B)
Figure 2.2 Stages in the progression of rheumatoid arthritis
Figure 2.3 Involvement of joint sites in established rheumatoid arthritis
Figure 2.4 Non-articular manifestations of rheumatoid arthritis
Figure 5.1 Percentage change in the prevalence of rheumatoid arthritis in major world markets, forecast to 2020
Figure 5.2 Percentage change in the prevalence of psoriasis in major world markets, forecast to 2020
Figure 5.3 Percentage change in the prevalence of ulcerative colitis in major world markets, forecast to 2020
Figure 5.4 Percentage change in the prevalence of Crohn's disease in major world markets, forecast to 2020
Figure 5.5 Market share by company for multiple sclerosis drugs, 1999�2000
Figure 5.6 Sales and forecast sales of Avonex, 1998�2002
Figure 5.7 Sales and forecast sales of Betaseron, 1998�2002
Figure 5.8 Market trend for celecoxib sales, projected to 2002
Figure 5.9 Market trend for leflunomide sales, projected to 2002
Figure 5.10 Market trend for biological therapies for inflammatory bowel disease, 1998�2002
Figure 5.11 Market share by company for inflammatory bowel disease drugs
EXECUTIVE SUMMARY
Autoimmune diseases are a diverse group of more than 80 chronic disorders which can attack virtually any tissue or organ system in the body. Many are rare, but others are not and, as a group, they represent an increasingly important class of medical conditions which affect a significant proportion of the world population. According to the American Autoimmune Related Diseases Association, approximately 50 million Americans (20% of the population) suffer from some 80 autoimmune diseases; consequently, as a group, their impact on the healthcare budget cannot be ignored.
In all autoimmune diseases, the underlying cause is the same: the body's immune system, which, under normal conditions, controls the body's defences against infection from outside the body, mistakenly attacks itself, targeting its cells, tissues and organs from within. In the resultant T cell-dependent response, antibodies, known as autoantibodies, are produced, and these attack host antigens, causing inflammation and immunological damage to tissues where these host antigens occur. The cause of the attack is unknown, although it is believed to involve viruses and environmental factors such as exposure to sunlight, certain chemicals and some drugs, all of which may damage or alter cells so that they are no longer recognisable as self. Sex hormones appear be important too, because women are much more commonly affected than men.
Genetic factors are known to play a role in the aetiology of autoimmune diseases. Monozygotic twins do not always develop the same disease or develop it to the same degree, but the incidence of autoimmune disease among these individuals is often much higher than in people who are unrelated. Autoimmune reactions are influenced by genes of the major histocompatibility complex, and a significant number of individuals with autoimmune disease have particular histocompatibility types. For example, people suffering from rheumatoid arthritis (RA) possess the self marker HLA-DR4.
Autoimmune diseases affect the body in many different ways. In multiple sclerosis (MS), for example, the autoimmune reaction is directed against the brain and spinal cord, whereas in Crohn's disease and ulcerative colitis (collectively referred to as inflammatory bowel disease) it attacks the gut. Other systems that can be the subject of autoimmune attack include the blood, blood vessels, skin, the musculoskeletal system (as in RA) and, the endocrine glands. The damage caused to tissues tends to be progressive, and, in some situations, can be complete, as with the destruction of insulin-secreting pancreatic cells in type 1 diabetes and thyroid hormone-secreting cells in Hashimoto's disease. In diseases such as systemic lupus erythematosus (SLE), a multiple organ disease caused by an excess of antinuclear antibodies, virtually any tissue or organ can be affected, and the extent and severity of the disease can differ widely between individuals. Here, antinuclear antibodies link up with self-antigens to form circulating immune complexes that become lodged in body tissues, and initiate widespread inflammatory reactions.
Approximately 75% of cases of autoimmune disease occur in women. In total, autoimmune diseases represent the fourth largest cause of disability among women in the US and at least the eighth leading cause of death in women aged 15�64 years of age.
Autoimmune diseases follow a relapsing-remitting pattern. They are usually chronic, and require lifelong management, but with the appropriate care, people can still lead normal lives. The aim of current treatments is to prolong the periods of remission and to reduce the frequency and magnitude of relapses. Where permanent damage occurs, as in type 1 diabetes and Hashimoto's disease, lifetime hormone replacement therapy is required. Patients with type 1 diabetes are managed with insulin to control blood glucose concentrations, while, for those with Hashimoto's disease, thyroid hormone replacement is the focus of the management programme. Other diseases, for example, SLE, MS and RA, are managed with anti-inflammatory and immunosuppressive drugs to slow or stop the immune system's relentless destruction. The drugs that are commonly used include non-steroidal anti-inflammatory drugs (NSAIDs) to relieve pain and reduce inflammation, corticosteroids and immunomodulatory cytotoxic drugs. These drugs are far from ideal, because they are non-specific and have an undesirable overall effect on the immune system, or, in the case of NSAIDs, on the gastrointestinal system. The aim of pharmaceutical research, therefore, is to develop drugs which will establish disease remission, but without the side effects of these non-specific drugs. Much current research is directed towards finding drugs that target specific steps in the inflammatory response, and it is here that the development of biological drugs leads the way.
Progress in the treatment of MS has recently been achieved with immunomodulatory biological drugs, namely the interferons (IFN-ß1a and IFN-ß1b) and glatiramer acetate (formerly copolymer-1). These drugs have revolutionised MS management and indeed, the MS drug market.
The role of tumour necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, in the inflammatory process, and its implication in the pathogenesis of several autoimmune diseases, has made it a therapeutic target for drug development. Etanercept (Immunex's Enbrel) is a TNF receptor p75 fusion protein that competitively inhibits the binding of TNF to its receptor, thereby inhibiting its pro-inflammatory action. This drug is already launched for the treatment of RA, and promises to contribute a novel alternative to the current disease-modifying anti-rheumatic drugs, possibly replacing them in the future. Two other TNF-alpha antagonists, infliximab (Centocor's Remicade) and D2E7 (Knoll) differ, in that they are monoclonal antibodies that specifically target TNF-alpha. All three drugs represent a major advance in the management of diseases such as RA and Crohn's disease, but they are not without side effects, and their potential has yet to be demonstrated, particularly with respect to disease progression.
The ultimate aim of pharmaceutical research is to produce drugs which will prevent autoimmune diseases, and block or regulate inflammatory pathways. Such drugs would have significant market potential, but a lack of knowledge and the complexity of autoimmune disorders has led, in the recent past, to a large number of drugs failing in development. However, as a result of better understanding of the basic mechanisms of autoimmune disease and increased insight into the influence of genetic factors, significant therapeutic advances are in sight. Smaller biotechnology companies have joined the race to develop these products, and recent developments promote optimism that new and successful treatments are giving rise to an emerging market.
The present report focuses on six autoimmune diseases, all of which have a high profile, as there are developments in the therapeutic management of them. These include diseases for which new biological therapies are now available (RA, MS, Crohn's disease and ulcerative colitis), and diseases where, although no new drugs have been available for decades, there is the promise of some novel treatments on the horizon (SLE and psoriasis).
The scope of the report is extended to briefly discuss other autoimmune diseases which are common and therefore important, but for which there is little in the way of novel pharmacological treatment available at present. Some of the diseases included can be managed with hormone replacement, namely type 1 diabetes and Hashimoto's thyroiditis, and do not strictly fit into this category, but others depend only on established non-selective immunosuppressive therapies or non-pharmacological methods of management. The diseases covered are Sjögren's syndrome, a common chronic inflammatory autoimmune disorder of the lachrymal and salivary glands, and systemic sclerosis (or scleroderma), a painful, incurable, multi-system autoimmune disease which presents as a leathery thickening of the skin and blood vessels. Graves' disease, also referred to in the report, is a type of hyperthyroidism that can be treated with antithyroid drugs, radioiodine or surgery. Other disorders featured are autoimmune hepatitis, which is the result of an autoimmune attack on the liver, causing inflammation and liver cell death, and myasthenia gravis, an autoimmune disease that attacks the neuromuscular junction, often with devastating results.
The report also provides a breakdown of the value of the market for drugs for selected autoimmune diseases, and presents comprehensive epidemiological data for the specified disorders. It contains 17 company profiles, representing a cross-section of the companies marketing and developing therapies for autoimmune diseases. These profiles give information on the background of the companies, agreements regarding autoimmune diseases therapies, financial highlights and details of the relevant drugs marketed and in development.
© PJB Publications Ltd. 2001
All rights reserved.