Paul Verweij, a doctor-scientist at the Radboud University Medical Center, is used to deal with very sick patients. As a professor of medical microbiology, it was his job to identify dangerous pathogens so the right treatments could be prescribed.
One group of patients had the kinds of serious illnesses that are common in an intensive care unit: blood cancer, immune disorders, end-stage lung disease. But on top of that, they all suffered from a fast-growing, life-threatening invasion of an environmental fungus called Aspergillus fumigatus. In the past, a class of drugs called azoles had reliably cured aspergillus, but these fungal infections were oddly drug-resistant. Five out of six patients died.
Revolutionairy antifungal drug
A potentially revolutionary antifungal drug, called olorofim, is at risk of becoming ineffective before its release due to the prior use of a similar agricultural compound (ipflufenoquin). Developed by British firm F2G, olorofim targets a novel mechanism for treating Aspergillus and valley fever; however, ipflufenoquin, made by Nisso America, shares the same molecular pathway. This raises concerns about fungal resistance, as fungi adapt quickly to protect themselves against new treatments. With 1.5 million deaths annually from fungal infections worldwide, medical professionals are eager for new antifungal drugs, as current options are limited and often toxic. The situation highlights the urgent need for cooperation between medicine and agriculture to ensure the effectiveness of new antifungal treatments, and the establishment of a federal agency or international body to assess risks and priorities.
The Growing Threat of Fungal Resistance
Fungal infections are a significant global health concern, with at least 300 million people contracting them each year and 1.5 million succumbing to the infections. They pose a similar threat as malaria or tuberculosis, and their incidence and range are expected to increase as the planet warms. In the US alone, fungal infections are responsible for over 75,000 hospitalizations and $7.2 billion in healthcare spending annually.
Developing antifungal drugs is a challenging task, as fungi share many cellular similarities with humans. This makes creating drugs that target fungi without harming humans difficult and often results in toxic side effects. For example, amphotericin B, an older antifungal drug, is notorious for causing tremors and fevers in patients.
Olorofim: A Promising New Antifungal Drug
Olorofim, currently in phase 2 trials, represents a new class of antifungal drugs called DHODH inhibitors. It has been in development for over a decade and has received the FDA’s “breakthrough therapy” designation, fast-tracking it to address a critical unmet need. Medical professionals have been eagerly awaiting olorofim, as it promises to provide a novel and effective treatment for Aspergillus and valley fever, affecting up to 150,000 people in the US each year.
However, last summer, it was discovered that olorofim was not the first DHODH inhibitor to be introduced in the US. The agricultural fungicide ipflufenoquin, which shares the same molecular pathway as olorofim, was approved by the US Environmental Protection Agency. This raised concerns among olorofim’s developers that the agricultural compound’s deployment might threaten the drug’s effectiveness before it even enters the market.
Striking a Balance Between Medicine and Agriculture
Both medicine and agriculture require new antifungal treatments, but the introduction of novel compounds creates a race against time, as fungi adapt quickly to protect themselves. The first sector to deploy a new treatment will benefit the most, but there is currently no federal agency or international body to assess risks, establish priorities, or ensure cooperation between the two disciplines.
As the global threat of antifungal resistance grows, medicine and agriculture must work together to develop risk assessment measures and strategies to prevent resistance. This collaboration is crucial in the context of One Health, which emphasizes the interconnectedness of human, animal, and environmental health. As the World Health Organization declared its first-ever list of priority fungal pathogens in 2022, the need for a united approach to combatting fungal resistance has become increasingly urgent.
Sources Laio used to write this article:
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