Merck & Co/Amrad: an uncertain pathway to success

Asthma is a common chronic disorder of the airways that afflicts up to 150 million people globally, according to the World Health Organization. Although symptoms in many patients are controlled with current standard of care, around 20% of asthma sufferers across the , , , , and have a form of severe asthma that represents a significant unmet medical need. Although this group represents a small percentage of all asthma patients, it accounts for much of the morbidity, mortality, and cost of the disease.

Monoclonal antibodies offer promise

Many of the mediators implicated in the pathophysiology of asthma appear to be excellent targets for monoclonal antibody (mAb) intervention, and the infrequent dosing regimen of mAbs, which may only need once- to twice-monthly dosing, is a major advantage. The first mAb therapy approved for the treatment of severe asthma was Novartis and Genentech's Xolair (omalizumab), an anti-IgE antibody, which was launched in the in 2003.

However, Xolair is only indicated for use in patients with atopic, or allergic, asthma, who represent around 40% of the total adult severe asthma population. A novel mAb that can prove effective in both atopic and non-atopic asthma could have sales potential in excess of $1 billion, according to research conducted by Datamonitor.

The race is on

Studies in animal models have revealed a pivotal role for IL-13 as a mediator of the inflammation and fibrosis associated with asthma, suggesting that it is an important therapeutic target for severe asthma. In 2003, in one of the largest biotechnology collaborations in Australian history, Merck licensed Amrad's technology for an IL-13 monoclonal antibody, which has now been selected for full preclinical development. Datamonitor estimates that the drug candidate will enter clinical development in late 2006, or early 2007.

The race is on for Merck and Amrad, however, as this has proved an active area of research for other pharmaceutical companies: in July 2005, Cambridge Antibody Technology announced that its anti-IL-13 monoclonal antibody, CAT-354, was well-tolerated with no safety concerns identified in a phase I clinical trial in mild asthmatic patients. Centocor and Wyeth are also conducting preclinical work on developing therapies that could inhibit IL-13.

This interest is justified as, in addition to severe asthma, IL-13 may also be a promising therapeutic target for other respiratory conditions, such as idiopathic pulmonary fibrosis, a devastating disease affecting elderly patients that has a survival rate lower than many neoplastic diseases.

Question still remain concerning whether targeting a single pathway will ultimately prove successful, given the failure of other mAb therapies, including offerings from Protein Design Labs, GlaxoSmithKline and Schering-Plough, to demonstrate any clinical benefit. However, monoclonal antibodies for respiratory indications are very much in their infancy and as the industry gains experience in this area, the market certainly has the potential for further market expansion, which bodes well for Merck and Amrad.

Related research:

·          Pipeline Insight Asthma/COPD/Allergic Rhinitis - As Patents Expire, Novel Combinations Inspire

·          Stakeholder Insight: Asthma - Combination Therapy Appropriate for Everyone?

·          Respiratory Handbook 2005-15: Novartis Moving Into the Major League