Overview
About MGCD290.
MGCD290 is a novel antifungal therapeutic that inhibits the fungal histone deacetylase (HDAC) enzyme HOS2 which is involved in the transcription of fungal genes related to fungal virulence and the fungal cell wall. When combined with azole antifungals, a widely used class of drugs, MGCD290 shows dramatic synergy. It is being developed as a combination therapy with fluconazole, the most widely-used azole. In preclinical studies, MGCD290 was shown to:
- Increase the cidality (ability to kill fungal pathogens) of fluconazole
- Improve the spectrum of activity of fluconazole
- Be effective against azole-resistant pathogens
- Decrease the ability of fungi to become more virulent
- Be effective in combination with other azoles (i.e. voriconazole, itraconazole)
Clinical Status.
MethylGene has completed four Phase 1 studies in over 100 healthy adult volunteers with MGCD290. To date, MGCD290 has shown an excellent safety profile with no drug-drug interactions with fluconazole.
MGCD290 Clinical Trials.
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Next Steps.
Phase 2 clinical studies were initiated in Q4 2011 to assess MGCD290 in acute vulvovaginal candidiasis. A second trial in recurrent VVC is also planned for a later date.
About Acute Vulvovaginal Candidiasis.
Acute vulvovaginal candidiasis (VVC) is a yeast infection that is most commonly caused by the type of fungus known as Candida albicans, although Candida glabrata is thought to be the cause of 10-15% of infections. VVC affects an estimated 75% of healthy women at least once, 40-45% will have two or more episodes within their lifetime. A single dose of fluconazole is labeled for acute VVC, and is considered effective in the mild population. In women with moderate to severe infections, fluconazole has only a 30-50% success rate. Despite the medical need, few agents are currently in development.
About Recurrent Vulvovaginal Candidiasis (RVVC).
RVVC, a more complicated form of VVC, is defined as four or more episodes of VVC in one year1. In the U.S. 6 to 8 million women are affected and over one million women are affected in Canada2. Treatment for RVVC is typically with the antifungal drug fluconazole; however, treatment is often long-term (at least six months) and upon completion of treatment, there is a high relapse rate. There is no FDA-approved therapy for the RVVC indication, and few agents in development.
1. CDC 2011
2. Sobel JD, Curr Infect Dis Reports 2006 8: 481-486