MGCD290 is a first-in-class orally available small molecule inhibitor of the fungal enzyme Hos2. Hos2 is a fungal histone deacetylase (HDAC) enzyme HOS2 which regulates fungal genes.
MethylGene has completed five Phase I studies in over 100 healthy adult volunteers with MGCD290. A multicenter, randomized, double-blind, placebo-controlled, Phase II trial (trial 290-005) to assess MGCD290 in patients suffering from moderate to severe acute vulvovaginal candidiasis (VVC) was recently completed. This trial was designed to assess the effectiveness of MGCD290 in combination with fluconazole, as compared to fluconazole alone. This study showed no statistically significant benefit of MGCD290 plus fluconazole compared to fluconazole alone. MethylGene is reviewing the data and evaluating plans for the MGCD290 program.
About Vulvovaginal Candidiasis.
Acute vulvovaginal candidiasis (VVC) is a yeast infection that affects an estimated 75% of healthy women at least once, and 40-45% will have two or more episodes within their lifetime1. Predisposing factors include uncontrolled diabetes and immunosuppression. A single dose of fluconazole is labeled for acute VVC, and is considered effective in the mild population2. However, in women with moderate to severe infections, fluconazole has only a 30-50% success rate.
About Invasive Fungal Infections.
Incidence of invasive fungal infections have risen rapidly over the past 20 years6. Hospital-acquired infections of Candida species are associated with a 40% mortality rate and the contribution of drug-resistant species is rising7. Aspergillosis is another form of invasive fungal infection with a mortality rate as high as 85%8. Incidence of drug-resistant aspergillis isolates from hospital patients are rising and may reach over 30%9. The fastest growing populations at risk of invasive fungal infections include transplant patients, surgery patients, cancer patients, those on immunosuppressive therapy, cancer patients, premature babies and the elderly.
2. Infectious Diseases Society of America Guidelines, (2009)
3. de Leon et al., (2002) BMC Infectious Diseases 2:1
4. Centres for Disease Control, (2011)
5. Sobel, (2006) Current Infectious Disease Reports 8: 481
6. Pfaller & Diekema, (2007) Clinical Microbiology Reviews 20:133
7. Snydman, (2003) CHEST 123:500S
8. Pfaller & Diekema, (2006) CID 43:S3
9. Bueid et al., (2010) Journal of Antimicrobial Chemotherapy 65:2116