Two antifungal drugs advance

Pharmaceutical firms are making progress in addressing the need for new antifungal therapies.

F2G, which specializes in the treatment of rare fungal disease, says it will receive $100 million from the Japanese firm Shionogi in a deal to develop olorofim, an antifungal agent for invasive aspergillosis and other rare mold infections. This news follows the April 28 announcement by Mycovia Pharmaceuticals that the US Food and Drug Administration approved its azole antifungal Vivjoa (oteseconazole) for chronic yeast infections. The announcements reflect efforts to fill gaps in treating fungal infections, an area with limited treatment options and increasing resistance to some that exist.

F2G says olorofim is part of the first new class of antifungals to be developed in 20 years. F2G’s chief operating officer, Mike Birch, says the firm is preparing a New Drug Application for submission to the FDA later this year. The deal with Shionogi is focused on Europe and Asia.

Olorofim works by inhibiting an enzyme in the fungi’s pyrimidine biosynthesis pathway, preventing RNA and DNA formation and throwing fungal cells into “metabolic turmoil,” Birch says.

Birch says olorofim has an advantage over azoles, the current dominant class of antifungals. Azoles are “the gold standard therapy for invasive aspergillosis,” he says. They work by disrupting a different enzyme, one that is crucial to the fungal cell membrane’s integrity. However, he says their widespread use to combat agricultural pathogens has driven development of azole-resistant fungal infections.

“Pretty much every country in the world is seeing azole resistance at some level,” Birch says. Well-known azole-resistant fungi are susceptible to treatment with olorofim, he says.

David Andes, an infectious disease specialist at the University of Wisconsin–Madison who often works with immunocompromised patients, says olorofim shows promise for treating some increasingly resistant fungal pathogens. It will not be effective for all resistant pathogens, he says, but data suggest it will safely and effectively treat a subset of them for which there are no other treatment options.

Although Vivjoa, Mycovia’s new product, is an azole, the fungus that most commonly causes yeast infections rarely demonstrates resistance, Andes says. Compared to the current available treatment, he says, Vivjoa has several advantages, including its ability to stay in the body longer.

Andes says the two antifungal developments are significant on different levels. “One is an improvement on an existing class, but an advance. And the other is a completely new mode of action, and I get most excited about those.”