Antifungal Proves Potent Against New Strains of Candida & Aspergillus

SCYNEXIS recently presented data to demonstrate the versatility of its candidate SCY-078 which is currently in phase 2 trials, at the 2018 ASM Microbe meeting in Atlanta, Georgia.

SCY-078, the first representative of a novel oral and intravenous (IV) triterpenoid antifungal family has shown activity against Aspergillus and Candida pathogens. In addition to being a potential new treatment option for multiple fungal infections such as vulvovaginal candidiasis (VVC), invasive candidiasis (IC), and invasive aspergillosis (IA), it may also provide benefits for prophylaxis use and for the treatment of chronic or refractory fungal infections, according to the company.

“SCY-078 would be the only class of antifungals, other than the azoles, with an oral formulation. This is a critical feature because currently patients undergoing treatment for invasive fungal infections receive that treatment for 14-82 days,” David Angulo, MD, chief medical officer of SCYNEXIS explained to Contagion®. “Given the high and growing number of pathogens resistant to the azole class, there are currently patients who must return to the hospital each day to get IV therapy.”

SCY-078 inhibits the synthesis β-(1,3)-D-glucan, which is a critical component of the fungal cell wall of many harmful fungi. By inhibiting this, it compromises the ability of the fungi to survive. “Disruption of the fungal cell wall is fungicidal against Candida spp.,” Dr Angulo added. “The cell wall of fungi is a unique target not encountered in mammalian cells, which provides for the good safety profile of SCY-078 and other glucan synthase inhibitors,” as this limits the risk for an “off-target” effect such as human cell toxicity.

In a poster presentation, representatives from SCYNEXIS explained that SCY-078 remains active against organisms that are resistant to Caspofungin and that the drug demonstrated to have “a profound effect on cellular morphology in CAS-resistant organisms, which may be indicative of a difference in target engagement from the echinocandins.” Additionally, in a different poster presented at the meeting, representatives discussed how the candidate drug used in combination with Isavuconazole was found to be synergistic in vitro against many Aspergillus spp.

The mechanism of action of SCY-078 is different from that of azoles and polyenes; it is unique in that it allows retention of activity against azole and polyene-resistant strains, has a potential for a more favorable safety profile, has a lower risk for drug-drug interactions in comparison with azoles, has enhanced activity at acidic vaginal pH, and has synergistic antifungal activity in combination with azoles and polyenes, which is critical for the treatment of invasive aspergillosis (IA).

The US Food and Drug Administration has granted QIPD and Fast Track designations for the formulations of SCY-078 for the indications of IC, IA, and VVC, and SCY-078 has been granted Orphan Drug Designation for the IC and IA indications.