Pfizer signs asthma and COPD deal
to develop a novel class of compounds for the treatment of allergic
asthma and other respiratory diseases that continue to see cases
rising in Europe and the US.
Asthma is now one of the world's most common long-term conditions, affecting as many as 300 million people worldwide. This number could increase by a further 150 million by 2025, according to the World Health Organisation (WHO).
Under the terms of the agreement, Rigel will receive an upfront cash payment, as well as milestone payments and royalties on any future product sales. Pfizer will make an equity investment in Rigel and will be responsible for the worldwide development and commercialisation of any resulting products. Financial terms of the agreement were not disclosed.
The collaboration aims to further develop Rigel's preclincal small molecule compounds, which inhibit the IgE receptor signalling in respiratory tract mast cells by blocking the signalling enzyme Syk kinase.
Rigel has pioneered the discovery of treatments for allergic diseases by blocking Syk kinase. The company was the first to discover and develop potent and selective Syk inhibitors and introduce these into the clinic.
The small molecules' mechanism of action causes them to bind to and inhibit Syk kinase, an intracellular target that regulates IgE receptor signalling in mast cells and thus prevent cellular activation and subsequent release of multiple chemical mediators.
However, unlike common allergy and asthma drugs that block only a single chemical mediator, Syk inhibitors block the major IgE dependent pathways in mast cells that trigger an allergic attack, potentially making Syk inhibitors more effective and comprehensive drugs.
Currently, steroids are the only other non-injectable class of agents that block multiple chemical mediators in the allergic response, but these have a slow onset of action. Although these treatments are effective patient compliance is poor, especially with respect to inhaled treatment. In addition 5 per cent of patients are unresponsive to these treatments accounting for a large segment of asthma related healthcare costs.
Short-term advances in the market are likely to centre on combination products. GlaxoSmithKline's bronchodilator-corticosteroid combination drug, Advair has been successful offering improved efficacy. Currently treatments are inhaled and since compliance with inhaled corticosteroid therapy, is very poor (estimates of non-adherence of between 30 per cent and 70 per cent have been reported) longer term goals are to develop orally active agent with acceptable side effect profiles and also preventative therapeutics.
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.
The Syk tyrosine kinase as a target for asthma is at the centre of major changes occurring in the field of asthma therapeutics. This is nowhere more clearly illustrated than by the big pharma companies that have released a selection of therapies based on this emerging target.
Martin Mackay, senior vice president, research & technology for Pfizer was himself quoted as saying: "Inhibition of Syk kinase is a novel approach to reduce the chronic inflammation in patients with allergic diseases of the respiratory tract such as allergic asthma."
Novartis announced last summer that the US Food and Drug Administration (FDA) had approved the novel IgE-blocker Xolair (Omalizumab) for the treatment of moderate-to-severe persistent asthma in adults and adolescents. At the same time Merck Sharp & Dohme announced that they have agreed to fund Amrad with an upfront payment of $7.4 million (€5.6 million), and potentially up to $167 million (€128 million) plus royalties, to advance its early-stage biological treatment for asthma.
The Centres for Disease Control and Prevention (CDC) estimates that direct costs to the United States for asthma management and treatment is nearly $15 billion on an annual basis. Chronic obstructive pulmonary disease (COPD), a group of diseases that cause airflow blockage and breathing-related problems, is currently the fourth leading cause of death in the US, according to the American Lung Association.
According to Datamonitor, the world market for asthma/COPD drugs is valued at $13.3 billion in 2003, forecast to grow to $19.0 billion by 2009. Such is the pace of the market and the rising incidences in children, annual growth rates of 10-15 per cent have been reported.
