US fungicide approval threatens effectiveness of new British drug

Expert says it is “absolutely necessary” for agrochemical companies and regulators of antifungal products to thoroughly investigate their impact on human health

The US approval of a new fungicide (ipflufenoquin, trade name Kinoprol) for use in agriculture could have unintended consequences for human health.

Ipflufenoquin has been developed to combat fungal diseases of crops such as almonds, apples and pears, but scientists at the University of Manchester say its release could have a “devastating” effect on a new drug for human health.

That’s because, alongside the development of ipflufenoquin has come a broadly similar drug for human health. Olorofim, developed by the British firm F2G – a spin-out company from the University of Manchester – is a potential new treatment for aspergillus, which is caused by breathing in fungal spores. Spores from the fungus are found in commercial compost, flower beds, garden soil and in damp homes.

Aspergillosis kills around a million people each year globally. People with poorly functioning immune systems such as transplant patients, those undergoing chemotherapy, individuals with COPD, or those with severe flu or Covid infections, are particularly at risk of infection.

While Olorofim demonstrates high effectiveness against fungal infections in humans, studies at the University of Manchester have shown that exposure of aspergillus to ipflufenoquin encourages the rapid evolution of resistance to Olorofim.

Dr Norman van Rhijn, a Research Associate in the Manchester Fungal Infection Group said: “When we found out that regulatory approval was sought for ipflufenoquin and its mode of action was the same as Olorofim, we immediately felt alarmed.

“Scientists have long known that environmental use of fungicides has the potential to drive resistance to clinical antifungals. Drug resistance increases the risk of death from aspergillosis from 40% to 80%.”

“It is devastating that the efforts that so many have made in the development of Olorofim are being put at risk.”

Professor Mike Bromley, a former employee of F2G and co-lead of the Fungal AMR and One Health Network, said: “It is devastating that the efforts that so many have made in the development of Olorofim are being put at risk.

“We have made our views clear to the Environmental Protection Agency in the USA and hope it will re-evaluate its approach to the environmental release of fungicides.”

David Denning, Professor of Infectious Diseases in Global Health at the University of Manchester and Scientific Advisor to the Fungal Infection Trust, said that resistance in fungi, especially aspergillus, has been a “consistent concern” for the Trust.

He said: “It is now absolutely necessary for agrochemical companies and regulators of their antifungal products to thoroughly investigate, ahead of approval for use in agriculture, the potential for negative consequences on human health related to the emergence of resistance.”

The House of Lords recently debated a question by Baroness Bennett of Manor Castle, which asked the government what assessment it made of how the UK’s current agricultural fungicide use will affect long-term food and biological security.

She told the chamber: “Managing fungal crop disease has always been essential to our ability to feed the population, but we cannot afford a haphazard, piecemeal approach that will hurt our public health and our NHS.”

Image credit: Shutterstock