Study Supports Development of a Vaccine for Recurrent Vulvovaginal Candidiasis

The fungal immunotherapeutic vaccine NDV-3A may be safe and highly effective when administered to women with recurrent vulvovaginal candidiasis (RVVC), according to a study recently published in Clinical Infectious Diseases.¹ 

At this time, RVVC is treated with repeated or prolonged antifungal therapy, which has variable efficacy, adds selective pressure for antifungal resistance, and poses specific safety concerns.^2,3 Therefore, the management of RVVC would be substantially improved with a safe and effective vaccine. This randomized, double-blind study (ClinicalTrials.gov identifier: NCT01926028) evaluated the immunotherapeutic vaccine NDV-3A containing a recombinant Candida albicans adhesion/invasion protein for prevention of RVVC. 

From July 2013 to May 2016, 188 women (aged 18-55 years) using an approved method of birth control and presenting with a clinically diagnosed active VVC episode at time of enrollment were included among 20 study sites in the United States. An active VVC episode was defined as having a composite sign and symptom score of 3 (range, 0-18), a vaginal swab culture-positive for C albicans, and at least 2 episodes of vaginitis during the 12 months before the current episode, 1 of which was documented by a diagnostic test specific for Candida.

Patients received 3 doses of 150 mg oral fluconazole taken on days −14, −11, and −8. Those with sign/symptom scores of 3 at day 0 left the study and were treated by their physician; those with combined sign/symptom scores of <3 were randomly assigned to a single intramuscular dose of either vaccine or placebo and were given 3 additional 150-mg doses for near-maximum immune response to the vaccine with minimal chance of influence of an active Candida colonization on days 0, 7, and 14. 

Results suggested that 1 intramuscular NDV-3A dose was safe and generated rapid B- and T-cell immune responses. In addition, post hoc exploratory analyses showed an increase of symptom-free patients at 12 months after vaccination compared with placebo (42% vs 22%; P =.03). Among patients aged <40 years (n=137), analyses showed a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo). Furthermore, the analysis of evaluable patients, which combined patients aged 40 years (23%) and <40 years (77%), suggested a positive effect of NDV-3A compared with placebo (P =.099). 

NDV-3A showed comparable adverse events compared with placebo. NDV-3A recipients showed slightly higher frequency in specific injection site reactions, which resolved in a few days, than placebo recipients, but these results were not statistically significant, although it did suggest elevated reactogenicity of NDV-3A. 

Overall, the study authors conclude that because results showed NDV-3A to be safe and highly immunogenic in women with RVVC, while it reduced the frequency of symptomatic episodes for up to 12 months, “these results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC.”

Disclosures: Several authors reported being employees and shareholders of NovaDigm Therapeutics.

References

1. Edwards JE Jr, Schwartz MM, Schmidt CS, et al. A fungal immunotherapeutic vaccine (ndv-3a) for treatment of recurrent vulvovaginal candidiasis-a phase 2 randomized, double-blind, placebo-controlled trial [published online April 25, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy185

2. Howley MM, Carter TC, Browne ML, Romitti PA, Cunniff CM, Druschel CM; National Birth Defects Prevention Study. Fluconazole use and birth defects in the National Birth Defects Prevention Study. Am J Obstet Gynecol. 2016;214:657.e1-657.e9.

3. Marchaim D, Lemanek L, Bheemreddy S, Kaye KS, Sobel JD. Fluconazole-resistant Candida albicans vulvovaginitis. Obstet Gynecol. 2012;120:1407-1414.