Asthma Therapeutics: New Treatment Options and Emerging Drug Discovery Targets
- ID: 28403
- April 2003
- Lead Discovery
From 1980 to 1996, the number of Americans afflicted with asthma more than doubled to almost 15 million, with children under five years old experiencing the highest rate of increase. The steady rise in the prevalence of asthma constitutes an epidemic, which by all indications is continuing. Even if rates were to stabilize, asthma would continue to be a profound public health problem, responsible for 9 million visits to health care providers per year, over 1.8 million emergency room visits per year, and over 460 thousand hospitalizations per year. As well as placing a considerable burden in terms of direct medical costs, asthma is one of the leading causes of work or school absenteeism. In 1990, the annual cost of asthma to the U.S. economy was estimated to be $6.2 billion, with the majority of the expense attributed to medical care. The epidemic in the US is representative of many developed countries.
Paralleling the dramatic growth in its incidence, asthma is driving one of the most rapidly growing global therapeutic markets. The impact that increased incidence is having on therapeutic market values is further exaggerated by a considerable degree of undertreatment of asthma. Global revenue for 2001 from asthma therapies has been reported by some to be as high as $11.7 billion and up until recently annual growth rates of 10-15% have been reported. Most sources however predict that this level of growth is not sustainable. Since the anti-asthmatic market is well served by existing therapies, such as the b2-agonists and corticosteroids which can treat 95% of asthma patients, competition within the anti-asthmatic market will grow increasingly intense. Consequently, to attain commercial success, pipeline products need to offer significant advantages over currently marketed therapies.
Short term advances in the market will center on combination products. GlaxoSmithKline's bronchodilator-corticosteroid combination drug, Advair has been particularly successful offering improved efficacy and convenience. Most currently used treatments are inhaled and since compliance with inhaled therapy, particularly with inhaled corticosteroid therapy, is very poor (estimates of non-adherence of between 30% and 70% have been reported) longer term goals are to develop orally active agent with acceptable side effect profiles and also preventative therapeutics.
This report produced by LeadDiscovery in collaboration with head of Thoracic Medicine at the National Heart and Lung Institute, asthma field-leader and panelist for the Global Initiative for Asthma (Gina), Professor Peter Barnes, focuses on the evaluation of emerging asthma therapeutics and provides a state of the art analysis of those drug discovery targets destined to underlie future therapeutics. This report is placed in the context of the asthma therapeutics market and current pharmaceutical development activity.
It has proved to be very difficult to develop new classes of anti-asthma therapy, partly because existing drugs, especially inhaled corticosteroids and combination inhalers, are so effective. New classes of therapeutics are expected to allow for oral treatment which will further improve patient compliance and possibly offer improved efficacy to treatment resistant patients. This report evaluates the major therapeutic targets currently under investigation offering an expert view of the potential and the limitations of each target. Such an evaluation is important to the success of drug discovery efforts since the asthma arena is characterized by targets that have initially offer promise but have failed to meet expectations in the clinic.
The only new class of drug developed in the last 30 years are anti-leukotrienes, which are far less effective than inhaled corticosteroids. New bronchodilators have been difficult to develop as new drugs are less effective than b2-agonists and have more side effects. Mediator antagonists have proved disappointing as so many mediators are involved in asthma.
A number of emerging targets are however especially promising including IL-13, Tace inhibitors, IL-10, dissociated steroids, PDE4, IgE and vaccine therapies. Proof of concept data and expert opinion on each of these targets is offered in this report. Many other targets are also discussed even though they have yet to be adequately investigated. For each of these, available data is provided and the risks associated with these targets are analyzed in order to guide future research.
The report concludes with a listing of therapeutics on the market or in development. Profiles are provided for those in advanced development or those that have been launched a strategic analysis is then provided underlining those targets perceived to be the most promising and how these targets should be exploited.
About the contributors to this report
Dr Jon Goldhill: Dr Jon Goldhill has over 10 years of academic and industrial research experience including 5 years in middle management at the French pharmaceutical giants, Sanofi-Synthelabo. Focussing on a variety of indications including inflammatory disorders, GI disease, Urological conditions and cancer, Dr Goldhill was responsible for target identification and project development. Dr Goldhill is now CEO and chief analyst at LeadDiscovery and coordinates the identification of candidate drug discovery projects with industrial potential.
Prof Peter Barnes: As head of Thoracic Medicine at the National Heart and Lung Institute (a division of Imperial College Faculty of Medicine) and Panelist for the Global Initiative for Asthma (Gina), Professor Peter Barnes represents perhaps the leading voice in respiratory tract disease. Professor Barnes has built a research group of approximately 70 basic scientists and clinicians dedicated to studying the mechanisms and treatment of asthma and other chronic airway diseases. The department has adopted a multidisciplinary approach, encompassing molecular biology, cell biology, in vitro pharmacology and in vivo experimental studies through to clinical studies in patients with asthma. This group publishes approximately 100 peer review papers annually and have an annual grant income of £2-3 million. Consequently Professor Barnes and his team is in an excellent position to push forward the frontiers of asthma as well as Copd. SHOW LESS READ MORE >
<P>The increasing prevalence of asthma </P>
<P>The role of genetic factors in asthma</P>
<P>The role of infective agents in asthma</P>
<P>Asthma as an inflammatory disease</P>
<P>MODERN ASTHMA MANAGEMENT</P>
<P>Drugs which increase cyclic AMP</P>
<P>Drugs which increase cyclic GMP
K+ channel openers</P>
<P>Purine receptor modulators</P>
<P>CYTOKINES AND CYTOKINE INHIBITORS</P>
<P>Strategies for inhibiting cytokines
Inhibition of Th2 cytokines</P>
Inhibition of proinflammatory cytokines</P>
<P>Other CCR inhibitors</P>
<P>NEW ANTI-INFLAMMATORY DRUGS</P>
Transcription factor inhibitors</P>
MAP kinase inhibitors</P>
<P>p38 MAP kinase inhibitors
Tyrosine kinase inhibitors</P>
<P>Syk kinase inhibitors
Lyn kinase inhibitors
EGF receptor kinase
<P>Th2 cell inhibitors
Cell adhesion blockers</P>
<P>SPECIFIC ANTI-ALLERGIC DRUGS</P>
<P>PREVENTIVE STRATEGIES IN ASTHMA</P>
<P>Specific allergen vaccination (immunotherapy)</P>
<P>THE ASTHMA THERAPEUTICS MARKET</P>
<P>ASTHMA THERAPEUTICS DEVELOPMENT</P>
<P>Full listing of therapeutics on the market or in developement aranged by originating company, phase of development, pharmacology
Therapeutic profiles of marketed products
salmeterol + fluticasone
budesonide + formoterol
Therapeutic profiles of clincial stage products
CONCLUSIONS & STRATEGIC ADVICE </P>