Asthma Ab overcomes Phase I hurdle

Cambridge Antibody Technology (CAT) has announced positive results of its human anti-IL13 monoclonal antibody, to be used as a potential treatment for severe asthma. The Phase I clinical trial of CAT-354 represents research towards areas of unmet medical need.

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).

The trial, which commenced in September 2004, was a double blind, placebo-controlled, rising single dose intravenous study in 34 mild asthmatic patients. Preliminary results showed that CAT-354 was well tolerated at all doses and there were no identified safety concerns.

IL-13 is an interleukin (protein), which has potent immunomodulatory effects. It is primarily secreted by TH2 lymphocytes and is believed to be a highly relevant target molecule for asthma as a result of its potential role in airways obstruction, acute exacerbations and in chronic airways remodelling.

CAT-354 becomes the first CAT antibody optimised using CAT's proprietary ribosome display technology to enter clinical development and the latest CAT-derived antibody to enter clinical trials.

Based on these results, CAT is planning to start a clinical pharmacology study in the fourth quarter of 2005. This is being planned as a repeat dose allergen challenge study in patients with asthma.

"CAT-354 is an important product candidate for CAT and this trial was the first clinical step in its development as a potential treatment for severe asthma," said Patrick Round, VP development at CAT.

"We are now moving forward with plans for a second clinical trial," he added.

Asthma is predominantly managed with three classes of drugs: agonists, which limit the narrowing of the airways; inhaled corticosteroids, a class of drugs with anti-inflammatory effects as well as significant and extensive side effects at high doses; and a newer group of compounds, the leukotriene inhibitors, which antagonize the inflammatory response at its final stages.

Inflammatory mediators have attracted considerable attention especially IL-13. This cytokine is elevated in asthmatic airways and may even be the link between asthma and childhood RSV infection a factor known to predispose individuals to disease at later times in their life.

US researchers have now confirmed the central role that IL-13 plays in airway disease, showing that IL-13 provokes airway hyperreactivity and the infiltration of inflammatory cells. Of even greater importance neutralising IL-13 was able to reduce these phenomena. This suggests that IL-13 blockade may offer hope to asthma sufferers.

Along with CAT, there is only one other molecule being reported as being in development, Amrad's IL-13 receptor antibody. Amrad, together with Merck, is developing therapeutic monoclonal antibodies that target the IL-13Rá1 and that block or inhibit IL-13 activity.

In 2002, the total market for drugs to treat asthma was $7 billion (€5.8 bilion) and the asthma drug market is expected to grow to approximately $13 billion by 2012, this growth in large part driven by the launch of new biological treatments.