Yeast Infection Drug Bypassing Fluconazole Resistance Fails

Laird Harrison

October 18, 2013

SAN FRANCISCO, California — An investigational drug was no more successful than placebo in the treatment of vulvovaginal candidiasis in the first phase 2 trial of the agent, researchers report.

"There wasn't really any difference at the end of the day," Wole Olafisoye, MD, a second-year fellow at the SUNY Downstate Medical Center, in Brooklyn, New York, told Medscape Medical News.

Dr. Olafisoye presented the results here at IDWeek 2013.

Vulvovaginal candidiasis affects about 75% of healthy women at least once in their lives. Most cases are caused by Candida albicans. Of these, up to 8 million experience recurrent infections.

A standard treatment, fluconazole, might be losing its effectiveness because azole-resistant strains of C albicans and non-C albicans species are becoming more common.

 
There are reports that fluconazole resistance is becoming more common in patients taking long-term therapy.
 

MGCD290, an experimental drug under development by MethylGene, used in combination with fluconazole, reversed this resistance in laboratory experiments by inhibiting the Hos2 enzyme in the fungus. It also improved the survival of mice infected with resistant yeasts, and appeared to be safe in phase 1 human trials.

To test the effectiveness of MGCD290, the researchers recruited 220 women suffering from yeast infections. All the women received 1 dose fluconazole 150 mg. In addition, half the women were randomly assigned to receive MGCD290 540 mg and the other half, placebo.

At baseline, 3.5% of the fungal cultures in women treated with MGCD290 had strains of yeast resistant to fluconazole, as did 2.4% of those in women treated in the placebo.

After 28 days, women in the placebo group were just as likely to be cured as those in the MGCD290 group. That was true whether rate of therapeutic cure or the rate of mycologic cure was measured.

Table. Cure Rates at 28 Days

Infection and Treatment Group Therapeutic Cure Mycologic Cure
All of those treated
MGCD290 65.1% 55.8%
Placebo 58.8% 52.9%
Non-C albicans species
MGCD290 not reported 66.7%
Placebo not reported 14.3%
Severe vulvovaginal candidiasis
MGCD290 87.5% not reported
Placebo 44.4% not reported
C glabrata
MGCD290 100% 66.7%
Placebo 16.7% 16.7%

 

Dr. Olafisoye speculated that the concentrations of MGCD290 in the vaginal fluid might not have been sufficient to make a difference in the treatment. "You might have to use a higher dose," he said.

The number of adverse events did not differ significantly between the 2 groups, and none of the events were severe. Only 9 of these events in the MGCD290 group and 7 in the placebo group were attributed to treatment by the researchers.

In women infected with Candida glabrata, a mycologic cure was statistically more likely with MGCD290 than with placebo (P = .0476), but there were too few women in this category to reach a conclusion.

The trend toward a greater cure rate with MGCD290 was similar in women infected with non-C albicans and in those with severe vulvovaginal candidiasis. However, these numbers, too, were very small.

Cathy Watson, PhD, a candidiasis researcher at the University of Melbourne, in Australia, said that this research is important.

"There are reports that fluconazole resistance is becoming more common in patients taking long-term therapy," she told Medscape Medical News. "Other promising experimental treatments that have proven statistical significance against placebos are very thin on the ground, and immunotherapy and Candida vaccines have yet to show convincing results."

This study was supported by Mirati Therapeutics, the parent company of MethylGene . Dr. Olafisoye and Dr. Watson have disclosed no relevant financial relationships.

IDWeek 2013: Abstract 1330. Presented October 5, 2013.

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