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Down with the resistance
JERSEY CITY, N.J.— SCYNEXIS, a biotech company specializing in anti-infective therapies for difficult-to-treat and often life-threatening infections, recently announced that its investigational antifungal drug SCY-078 has been found in two in-vitro studies to be effective against a multidrug-resistant, life-threatening fungus which has been identified as an emerging global health threat.
SCY-078 is a triterpenoid, semi-synthetic derivative of the natural product enfumafungin—a structurally distinct and novel class of glucan synthase inhibitor—and is currently in Phase 2 clinical development for the treatment of fungal infections caused by Candida and Aspergillus species, two of the most common causes of bloodstream infections in American and European hospitals. The U.S. Food and Drug Administration granted Fast Track, Qualified Infectious Disease Product and Orphan Drug designations for the oral and intravenous formulations of SCY-078 for the indications of invasive candidiasis (including candidemia) and invasive aspergillosis.
The two new studies show that the drug may also be effective in treating a more serious, multidrug-resistant strain of one of these fungi, Candida auris.
While the threat of multidrug-resistant bacteria has been known for decades, scientists and health officials have only recently begun to raise the alarm about C. auris, which is showing increasing resistance to antifungal drugs, including azoles and echinocandins. The fungus was first identified in Japan in 2009, and the earliest known strain was found in 1996 in South Korea. C. auris infections have been reported from over a dozen countries, and the U.S. Centers for Disease Control and Prevention (CDC) have identified 77 cases in seven U.S. states as of May 12. The CDC estimates that infections with C. auris are associated with a mortality rate of approximately 30 to 60 percent (though that number is based on information from a limited number of patients).
The fungus forms biofilms on catheters, and, according to the CDC, the risk for infection with this yeast is greatest in patients who have been in the intensive care unit for a long time or have a central venous catheter placed in a large vein, and have previously received antibiotics or antifungal medications. In addition to ear infections (from which came the name auris, Latin for “ear”), it can cause wound or bloodstream infections.
The first systematic investigation of the fungus was undertaken by Dr. Mahmoud Ghannoum, professor and director of the Center for Medical Mycology in the Department of Dermatology at Case Western Reserve School of Medicine, and University Hospitals Cleveland Medical Center. The results of this study were published in February 2017, in the journal Antimicrobial Agents and Chemotherapy.
Examining 16 strains of C. auris collected from infected patients in Germany, Japan, Korea and India, Ghannoum and his team tested the isolates against a battery of 11 drugs, belonging to different classes of antifungals, to identify drug concentrations that could combat infection. While most samples proved at least partially resistant to drugs tested, those exposed to low concentrations of SCYNEXIS’ SCY-078 showed evidence of severe distortion and impaired growth.
Notably, given the way that the C. auris forms in IV catheters, the results also showed that SCY-078 reduced biofilms and biofilm metabolic activity at all concentrations tested.
Said Ghannoum, “Understanding the virulence of C. auris and showing that the investigational drug is effective may lead to the development of new medications to combat this emerging health threat.”
The results of the Case Western study were confirmed by another study by the Mycotic Diseases Branch of the CDC and published in May in Antimicrobial Agents and Chemotherapy. In this study, the in-vitro activity of SCY-078 was evaluated against a collection of 100 C. auris isolates from several countries, including India, Pakistan, Colombia and South Africa, representing each of the four known branches of the pathogen. Researchers found that SCY-078 showed potent activity against all strains at concentrations which would indicate potentially clinically relevant effect. The study also showed that SCY-078 retained activity against echinocandin-resistant C. auris isolates, illustrating that resistance to other glucan synthase inhibitors (echinocandin class) was not indicative of resistance to SCY-078.
“These results, taken together, provide further evidence of the effect SCY-078 may have in the treatment of C. auris infections, as well as its ability to address other difficult-to-treat infections in the broader Candida class,” commented Dr. Marco Taglietti, president and CEO of SCYNEXIS. “We believe the key attributes of SCY-078, including its broad-spectrum activity against resistant strains, formulation versatility, high tissue distribution, fungicidal activity and favorable safety profile, will enable the drug to have a therapeutic effect in a broad variety of serious fungal infections.”
The company is also considering developing SCY-078 as what might be the first treatment for recurrent vulvovaginal candidiasis (VVC), commonly known as a yeast infection, and has completed a Phase 2 proof-of-concept study in patients with VVC, with positive results.