- Guest speaker Dr Neil Stone
In this episode we discuss new antifungal classes / drugs that are in late stages of clinical development: ibrexafungerp, opelconazole, olorofim and fosmanogepix
<aside>
💡
Current challenges with existing antifungal armamentarium:
- Only 3 main classes of antifungal currently in clinical use (azoles, echinocandins and polyenes)
- Limited recent drug discovery - only 1 new class in last 2 decades (echinocandins) and 2 new agents in last decade (isazvuconazole 2015, rezafungin 2024)
- Therapeutic options further limited by drug-drug interactions, toxicity and limitations due to administration routes (eg. echinocandins are IV only)
- Emergence of drug-resistant fungal pathogens eg. Candidozyma auris and azole-resistant Aspergillus fumigatus
- Rise in infections caused by rare yeasts and moulds
</aside>
Ibrexafungerp
- First member of the novel triterpenoid antifungal drug class
- Approved by FDA in 2021
- Not currently licensed in the UK
Mechanism of action
- Shares same mechanism of action as echinocandins
- Inhibits 1,3-beta-D-glucan synthase enzyme → inhibits synthesis of 1,3-beta-D-glucan in the fungal cell wall → increased cell wall permeability → cell lysis
- Like echinocandins, fungicidal against Candida sp. and fungistatic against Aspergillus sp.
- Different binding site to echinocandins → limited potential for cross-resistance between ibrexafungerp and echinocandins
- Ibrexafungerp demonstrates potent in vitro activity against echinocandin resistant Candida spp. with FKS gene mutations
Spectrum of activity
See figure below
| Active |
In vitro activity against Candida sp., Aspergillus sp., Pneumocystis jirovecii, Alternaria spp., Cladosporium spp., some dimorphic fungal pathogens ** |
| Less active |
Scedosporium spp. and Lomentospora prolificans |
| Not active |
Mucorales spp., Fusarium spp. |
Indications
Ibrexafungerp was found to be effective for treatment of acute vulvovaginal candidiasis (VVC) and recurrent VVC in completed phase 3 clinical trials: