Isis enters first asthma drug development

Isis Pharmaceuticals has initiated development activities on its first drug for the treatment of asthma and related pulmonary diseases.

The drug, ISIS 369645, is a second-generation antisense inhibitor of the alpha subunit of the interleukin 4 receptor, IL4R-alpha. Inhibiting the production of the IL4R-alpha inhibits the activity of two important cytokines in asthma, IL4 and IL13 that regulate inflammation, mucus overproduction and airway hyper-responsiveness.

'We are very excited about taking our first inhaled antisense drug into clinical trials. ISIS 369645 is the first drug from our relatively new lung-directed inflammation programme to enter development and shows how rapidly antisense technology enables the screening, validation and prioritsation of gene targets and pre-clinical profiling of potential drug candidates,' said Dr Frank Bennett, Isis' vice president of Antisense Research. 'ISIS 369645 is one of many compounds that demonstrate unique pharmacological profiles in human inflammatory and pulmonary epithelial cells. Inhaled antisense has the potential to provide highly specific, potent and effective therapies for the treatment of asthma and other chronic pulmonary inflammatory diseases with the convenience of weekly administration.'

Isis has created a significant data portfolio to support ISIS 369645 as an attractive local treatment for asthma in pre-clinical studies. Isis has shown that a mouse-optimised antisense inhibitor of IL4R-alpha:

• potently reduces IL4R-alpha: mRNA and protein levels;

• reduces lung cytokine production and inflammation, and airway hyperresponsiveness in mouse models of asthma; and

• when delivered by inhalation, rapidly distributes to the airways and achieves therapeutic drug concentrations in multiple cell types with little systemic exposure.

Isis 369645 is one of numerous drug candidates the company is examining to target inflammatory diseases of the lung and the first to enter clinical development. The attractive profile of Isis' proprietary second-generation antisense drugs for aerosol delivery is an example of Isis' efforts to investigate and develop new methods of delivering antisense drugs that broadens the therapeutic utility of the technology.