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Thursday, April 11, 2019

Scynexis in spotlight with a weapon that may fight Candida auris superbug

When Marco Taglietti flew from Amsterdam to Milan earlier this week, a neighboring passenger happened to ask what he did for a living. Upon learning he was an infectious disease specialist, the passenger inquired whether he had come across the recent report about this “difficult-to-treat new fungus.” Upon disembarking, Taglietti slid into his Uber, when his driver professed an interest in his profession. The physician’s answer produced a now-familiar response: Have you heard about Candida Auris?

Such is the state of affairs. A comprehensive report by the New York Times last Saturday put the spotlight on a stubborn, difficult-to-diagnose and treat fungal infection: Candida Auris or C. auris. The largely drug-resistant microbe, which thrives in people with compromised immune systems, has emerged mysteriously across the globe, popping up in Venezuela, Britain, the United States and having taken root in India, Pakistan and South Africa.
Taglietti, who has helped bring 35 drugs to market with stints at Forest Labs, Stiefel Labs and Schering-Plough, runs a small biotech out of Jersey City, New Jersey called Scynexis $SCYX — ostensibly the only US drug developer with an antifungal in late-stage clinical development for the oft’ deadly pathogen.
“The CDC has been actually been talking about it for the last couple of years, making dire predictions…but apparently no-one was listening,” Taglietti said in an interview with Endpoints News.
More than 1 in 3 patients with invasive C. auris infection (for instance, an infection that affects the blood, heart, or brain) die, according to the CDC, which has deemed the pathogen a “serious global health threat.” As of February 28, the US agency has recorded 587 confirmed cases and 30 probable cases this year.
“C. auris attaches from person to person, to things, to clothes, to the walls. This is why the CDC is so concerned about this pathogen, its very sticky, very persistent and tends to spread,” Taglietti said, noting that the publishing of the NYT story inspired a series of reports globally that helped the fungus has permeated the cultural zeitgeist.
“From what we know, we are the only company assessing an investigational treatment in C. auris. I’m sure now, many others will follow.”
It has been decades since a fresh family of antifungals has come on to the market — at the moment there are three classes of antifungals in clinical use, including azoles and echinocandins.
The most popular antifungals in use today were introduced in the 1980s and this class is increasingly losing its potency, as fungal pathogens become more resistant. Scynexis’s lead experimental drug — ibrexafungerp — belongs to a new class of antifungals called glucan synthase inhibitors, and has shown to be effective against a broad range of of fungal infections, including resistant strains, Taglietti said.
Last October, the company initiated a late-stage open-label study called CARES in C. auris patients. In a presentation on Friday, Scynexis will present data at a medical conference on two patients who were successfully treated with the oral ibrexafungerp from the ongoing study, which has enrolled several patients so far.
The passage of the limited population pathway for antibacterial and antifungal drugs (LPAD) pathway — established by the 21st Century Cures Act — allows the FDA to approve certain anti-infective products on the basis of limited clinical data. Scynexis is working with the FDA to sort out how much ibrexafungerp data will make the cut for C. auris, Taglietti said.
The drug is also being tested for other infections. It is in a Phase III study for vaginal yeast infections. Topline data are expected in the first half of 2020, and if positive, the company expects to file a marketing application in the latter half of the year.
One of the biggest challenges facing the field of antifungal drug development is the lack of incentives, such as those afforded to companies in the antibacterial and antiviral space, Taglietti said.
When the company approached BARDA for funding, they were told antifungals were not a priority in Washington, he said. “I hope this awareness will now reach Washington.”
As superbugs flourish, the industry players contributing to the arsenal of antimicrobials are dwindling. Companies in the antibiotic space have their own set of troubles.
Drugmakers are enticed by greener pastures, compared to the long arduous path to antibiotic approval that offers little financial gain as treatments must be priced cheaply, and often lose potency over time as bacteria grow resistant. Beyond the incentives already in place to push drugmakers to develop antibiotics, there have been calls to bring on “pull incentives,” or policy measures to increase the value of a marketed antibiotic by rewarding drugmakers only after their antibiotic is approved by the FDA.
Taglietti does not see antifungals facing a similar hurdle. “There is a (bigger) need for antifungals, therefore they will not go the same way antibacterial sales have gone. The last antifungal approved in 2015 is making $150 million in its third year of sales…more than the last 4 or 5 antibacterials combined.”

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