A single dose of an investigational fungal vaccine, NDV-3A, was safe and reduced episodes of recurrent vulvovaginal candidiasis, or RVVC, in women up to 1 year after vaccination, according to results of a phase 2 trial.
“There is a growing need for vaccines that can prevent or treat conditions caused by Candida spp., such as Candida albicans, the major causative agent of RVVC,” John E. Edwards Jr, MD, emeritus chief in the division of infectious disease at Harbor-UCLA Medical Center, said in a press release. “The positive results in patients with RVVC represent the first demonstration of efficacy for any antifungal vaccine. These results encourage further development of NDV-3A against life-threatening invasive Candida infections, including those by the recently emerging, highly drug-resistant Candida auris.”
Each year, RVVC occurs in approximately 6% to 9% of women in the United States and 138 million women worldwide, according to Edwards and colleagues. More than 490 million women are affected by RVVC during their lifetime. The condition is currently treated with repeated or prolonged antifungal therapy, which the researchers said “has variable efficacy, poses specific safety concerns, and adds selective pressure for antifungal resistance.”
“Thus, a safe and effective vaccine would represent a substantial improvement in management of RVVC,” they wrote in Clinical Infectious Diseases.
The researchers conducted a randomized, double-blind, placebo-controlled trial from July 2013 to May 2016 to assess the safety and efficacy of NDV-3A (NovaDigm Therapeutics), which contains the N-terminal portion of the agglutinin-like sequence 3 protein of C. albicans — the cause of most vulvovaginal infections in women. The trial enrolled 188 women aged 18 to 55 years with RVVC at 20 U.S. sites. They were randomly assigned to receive the vaccine (n = 103) or placebo (n = 85) and followed for 12 months after vaccination. Because there is no FDA guidance on efficacy endpoints for a vaccine or immunotherapeutic agent for RVVC, the researchers used “exploratory” endpoints based on patient-reported symptom scores.
Edwards and colleagues reported that one intramuscular dose of NDV-3A generated rapid immune responses in patients. The vaccine was associated with fewer RVVC episodes compared with placebo. In patients younger than 40 years (77%), 42% of those who received the vaccine had no recurrences vs. 22% who received placebo (P = .03). The median time to the first symptomatic episode was twice as long among vaccinated participants (210 days vs. 105 days). However, vaccine efficacy decreased with increasing age. Although recurrences were less common among women aged 40 years and older in the intervention arm than those in the placebo arm, the finding was not statistically significant. The reason for reduced efficacy in older women remains unknown, according to the researchers. However, they noted that future trials may investigate the possible effects of perimenopause and related hormonal changes.
In a safety analysis, there was no significant difference in adverse events between study arms. Most patients who received NDV-3A and placebo had at least one injection site reaction (87.6% vs. 84.7%) that usually resolved within a few days. No grade 3 or greater adverse events were reported.
Edwards and colleagues concluded that additional studies will need to confirm clinical signs of mucosal infection; whether complete C. alibcans decolonization is necessary to prevent RVVC; and quality-of-life benefits associated with vaccination.
“These issues will be important considerations in the design of a phase 2b trial to establish reliable clinical endpoints for further evaluation of NDV-3A in women with RVVC,” they wrote. – by Stephanie Viguers
Disclosures: Edwards is a scientific founder of NovaDigm. Please see the study for all other authors’ relevant financial disclosures.