A new kind of drug to fight avian influenza that will not suffer from the same kind of resistance problems as current treatments should begin clinical trials within the next three years, according to researchers.
The UK’s Medical Research Council has just awarded a grant of £408,000 ($778,000) to continue the development of the compounds, which work in a slightly different way to the current neuraminidase inhibitors – Roche’s Tamiflu (oseltamivir) and GlaxoSmithKline/Biota’s Relenza (zanamivir) – that are currently being stockpiled by governments around the world on fears that a bird flu pandemic is just around the corner.
In December, the New England Journal of Medicine reported two cases of patients who died from the H5N1 strain of bird flu despite treatment with Tamiflu because the virus mutated to become resistant.
The new drug also targets neuraminidase, but blocks the enzyme by chemically reacting to a highly conserved portion of the molecule that is essential for it to carry out its function. Tamiflu and Relenza act by competing for the active site of the enzyme and prevent it from binding to its usual target on infected cells.
Rather than interacting with the molecules on the surface of the infected cell, the neuraminidase enzyme binds to the drug instead. The drug physically gets in the way and inhibits the action of the enzyme, according to the researchers
The MRC grant has been awarded to Andrew Watts from the University of Bath in the UK and Jennifer McKimm-Breschkin from Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO).
“Tamiflu and Relenza remain our best lines of defence against a flu pandemic, but we need to be working on better alternatives that do not suffer the same inherent resistance problems,” said Watts. He suggested that the lead version of their improved neuraminidase inhibitor could reach the market before resistance to Tamiflu and Relenza becomes a major problem.
The researchers are currently narrowing-down the class of molecules they have discovered to identify the best candidate for developing a drug. They will then need to refine the delivery mechanisms and begin trials that will ensure its efficacy in patients.
Fears of a bird flu pandemic have transformed the fortunes of Tamiflu, elevating it from a minor product at Roche to one of its major growth drivers. For example, the UK Government has spent £200 million obtaining enough Tamiflu to treat 14.6 million people, a quarter of the population. Sales of the drug grew 62% to 961 million Swiss francs ($785m) in the first half of this year.
Relenza, which has proved less popular largely because it is administered by inhalation rather than orally, brought in $24 million in the same period, more than double the amount in the first half of 2005.