Recurrent Vulvovaginal Therapy Completes Phase 2a Study

NovaDigm Therapeutics published data from a Phase 2a study that demonstrated a single dose of NDV-3A with alum adjuvant was safe, well-tolerated, immunogenic and efficacious, leading to reduced recurrences of vaginitis in patients with recurrent vulvovaginal candidiasis (RVVC).

While current RVVC therapies are effective at controlling acute infections, they do not control recurrences, without chronic antifungal suppression.

Approximately 90 percent of patients report onset of RVVC prior to the age of 40 years, says the Centers for Disease Control and Prevention (CDC).

NDV-3A is designed to potentially treat or prevent diseases caused by fungal and bacterial pathogens, including antimicrobial-resistant strains.

Recurrent vulvovaginal candidiasis is a debilitating disease of immunologically normal women.

The major causative agent of RVVC is Candida albicans.

The article, titled "A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis - A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trials," was published online in the journal Clinical Infectious Diseases.

"There is a growing need for vaccines that can prevent or treat conditions caused by Candida species, such as Candida albicans, the major causative agent of RVVC," commented John Edwards, M.D., first author of the study, Emeritus Chief, Division of Infectious Disease at Harbor-UCLA Medical Center and a scientific founder of NovaDigm.

"The positive results in patients with RVVC represent the first demonstration of efficacy for any antifungal vaccine.”

“These study results encourage further development of NDV-3A against life-threatening invasive Candida infections, including those by the recently emerging, highly drug-resistant Candida auris."

NDV-3A is being developed as an immunotherapy and as a preventative vaccine for infections caused by several species of the fungus Candida.

Nine million women in the United States (11%) report having recurrent yeast infections, with approximately seven million (9%) experiencing RVVC.

RVVC has been defined as having three or more episodes per year.

"Women who have recurrent vulvovaginal candidiasis have limited options to maintain control of this chronic condition, which can have a significant impact on their health and overall quality of life," said Paul Nyirjesy, M.D., Professor of Obstetrics and Gynecology and of Medicine at Drexel University College of Medicine, who was a principal investigator in the a multi-center, double-blind, randomized, placebo-controlled, Phase 2a study.

"The results of this trial demonstrate increases in recurrence-free time out to 12 months for younger women based on patient symptom scores following a single dose of NDV-3A. This finding represents a potential breakthrough for an immunotherapeutic approach to treating these patients."

Top-line results reported in August 2016 show the study of 188 patients met its primary endpoint of safety and tolerability. There were no significant differences between NDV-3A and placebo for injection site reactions and systemic reactions of grade 3 or greater.

A single dose of NDV-3A generated rapid and robust immune responses. Younger patients showed higher efficacy rates.

In patients under 40 years of age (77% of the study population), 42% of NDV-3A recipients were recurrence-free at 12 months post-vaccination compared to 22% of placebo recipients (p=0.03). Patients in this age group receiving NDV-3A also showed a doubling in median time to first recurrence (210 days) compared to placebo recipients (105 days).

This research was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (Grant Numbers AI19990, AI063382, and AI071554) and by the Department of the Army (Award Numbers JW81XWH-10-2-0035, W81XWH-11-1-0686 and W81XWH-16-C-0125).

The researchers did not disclose conflicts of interest.