Breathing new life into old asthma drug

An ageing drug for asthma marketed by Abbott Laboratories could get a new lease of life from a revamp using drug delivery technology developed by SkyePharma of the UK.

Abbott sells the drug, called zileuton, in an oral formulation called Zyflo Filmtab that requires four times daily dosing. A small US company called Critical Therapeutics has now licensed rights to use zileuton in a new formulation developed by SkyePharma that will reduce the dosing rate and make it a more attractive treatment option for patients.

Zileuton was first introduced in 1997 as one of the first alternatives to steroids in asthma. Despite its early promise, the drug was held back by its onerous dosing regimen that reduced patient compliance with therapy and, in turn, asthma control. The drug was also associated with liver toxicity which meant that patients taking it required monitoring

Meanwhile, Zyflo soon lost out to rival products with similar but more selective mechanisms of action. It inhibits the inflammation that underlies asthma by inhibiting an enzyme, 5-lipoxygenase, that produces inflammatory mediators called leukotrienes. At around the same time, selective inhibitors of leukotriene receptors from Merck & Co (Singulair; montelukast) and AstraZeneca (Accolate; zafirlukast) were also launched, and Zyflo's position as the first steroid-sparing drug for asthma was effectively undermined.

Singulair and Accolate won the marketing battle with their once-daily dosing and cleaner side effect profile - both eventually turning topping $1 billion in annual sales.

Critical Therapeutics believes it can tackle at least the dosing issue with the SkyePharma formulation, and there is also a possibility that a controlled-release formulation could also alleviate some of the liver toxicity seen with the original compound. But even if this is not the case zileuton could see a new lease of life in the new formulation.

Abbott does not record the sales of Zyflo, but they are thought to be a few tens of million dollars a year - small change for a company ranked 12 in the pharma industry with sales of nearly $10 billion in 2002, but a significant product for Critical Therapeutics.

The US biotechnology company has no therapeutics on the market at present, and an improved version of zileuton could top up its coffers while it develops the novel drugs in its pipeline, as well as bringing in a useful new royalty stream for SkyePharma.

And there is a chance that Zyflo itself - which Abbott is not including as part of the deal - could see something of a renaissance. Abbott has an ongoing collaboration with French genomics company Genset to identify ways of identifying the 4 per cent of patients prone to develop liver side effects with the drug before they start treatment.