Doctors Stymied In Fungi Drug Research.

"Dangerous fungi are advancing faster than drugs to contain them.

Like bacteria, fungi are adept at mutating defenses against efforts to kill them. And designing antifungals is hard: Because the cells of mammals and fungi are similar, people often experience toxic side effects from drugs meant to hurt fungi.

Despite the challenges, some new antifungal drugs are in the works. The Food and Drug Administration approved Scynexis's ibrexafungerp in 2021 to treat vaginal yeast infections. The drug is being tested against more severe diseases. Pfizer is developing an antifungal called fosmanogepix for severe infections.

Another, F2G's olorofim, has shown promise against severe, hard-to-treat fungal infections in clinical trials. F2G said on June 19 that the FDA had rejected an approval application and asked for more data on the drug. The company said it would apply again with data from more patients and that additional trials are under way. The FDA said it doesn't comment on products it hasn't approved.

Even as studies of olorofim's effectiveness continue, a fungicide with a similar chemical structure is threatening olorofim's potency, fungal-disease experts said.

The Environmental Protection Agency last year approved Nippon Soda's ipflufenoquin to target fungal disease in almonds and fruit. The crop fungicide and olorofim block the same enzyme critical to the survival of some fungi. Laboratory research suggests exposure to the crop fungicide could trigger fungi to develop resistance to olorofim.

Nippon Soda didn't respond to requests for comment.

"We desperately need new drugs," said Dr. Tom Chiller, head of the Centers for Disease Control and Prevention's fungal-disease branch.

Chiller said more research was needed into how the use of fungicides could influence the impact of new antifungal drugs.

Jonathan Ferretti and his physicians credit olorofim for saving his life. When he was 17, Ferretti was diagnosed with acute myeloid leukemia. He underwent chemotherapy that decimated his immune system before a rare mold called scopulariopsis infected his bloodstream.

Dr. Andrej Spec, an infectious-disease specialist at Washington University in St. Louis, said he had treated about 20 other patients with such infections over the past decade. None survived, and most died within a week or two, he said.

Spec enrolled Ferretti, now 20, in a clinical trial treating patients with olorofim.

The infection started to clear within days, and he soon recovered. Ferretti's cancer is in remission, and he is working toward applying to nursing school.

Spec said the new crop fungicide could push some fungal pathogens to develop resistance to the new class of drugs including olorofim.

"If we lose this drug, I will have to tell patients, 'I'm very sorry but you're going to die,'" he said.

Public-health experts expect drug-resistant fungal and bacterial infections to surge in the years ahead. Some 35,000 people in the U.S. die from such infections every year, according to the CDC.

Researchers in the 2000s showed that widespread use of a different type of fungicide reduced the efficacy of antifungal drugs known as azoles against Aspergillus, a ubiquitous mold that can cause severe disease." [1]

1. U.S. News: Doctors Stymied In Fungi Drug Research. Mosbergen, Dominique. 
Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 27 June 2023: A.3.