Breathless opportunities

Treatment of asthma has remained essentially unchanged for years and focuses on alleviating symptoms rather than disease modification. In large part, the state of the art reflects inertia on the part of the dominant big pharma players, who are focused on wringing out profits from respiratory drug franchises that topped $15 billion in total sales in 2004. But advances also have been slowed by a lack of understanding of the causes of the disease and the fact that so many molecules appear to play a role in it.

Thus, the field today is where cancer was about a decade ago.

"Thinking in the past 30 years has been dominated by the leading two or three companies in the industry, but the existing treatments do little more than suppress the symptoms or inflammation, rather than modifying the outcome of the disease," said Stephen Holgate, Medical Research Council clinical professor of immunopharmacology at the University of Southampton in the U.K.

The existing paradigm for treating asthma is to give patients a combination of existing long-acting beta 2 agonist (LABA) bronchodilators and anti-inflammatory inhalable corticosteroids (ICS). While the vast majority of patients are well controlled with this regimen, the World Health Organization (WHO) estimates more than half the health costs of asthma are associated with the 5% of patients who have severe, persistent asthma that is poorly controlled.

In addition, an FDA warning issued last summer suggested that LABA containing therapies like Serevent salmeterol and the ICS/LABA combo Advair/Seretide may increase the chance of severe asthma episodes, as well as the chance of death when such episodes occur.

Holgate, who also is CEO and founder of Synairgen plc (LSE:SNG, Southampton, U.K.), believes that industry has been too complacent in its attitude toward asthma.

"There is still a misguided view that all we need is more inhaled steroids and long-acting beta 2 agonists. Yet the problem with these drugs is that patients have to continue taking them, often for life, since they either only suppress inflammation or relax smooth muscle without dealing with the underlying causes of the disease," he told BioCentury. "Clinicians want therapeutics that target the underlying causes of the disease."

In fact, potentially disease modifying approaches against new targets are in development at a number of biotech companies. The approaches include targeting a range of cells and molecules involved in this complex disease, among them IgE; a host of cytokines, chemokines and their

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