Candida is a genus of approximately 50 yeast (fungal) species, which includes Candida albicans, Candida glabrata, Candida krusei and Candida tropicalis, among others. Candida albicans is the predominant species responsible for vulvovaginal candidiasis (VVC), also called vaginal yeast infections, and the oral infection known as thrush—conditions that, while not life-threatening, have a significant negative impact on patients. Some women with VVC develop chronic, recurring cases of VVC, which is called recurrent VVC (RVVC). Women who have at least four episodes of VVC within a year suffer from RVVC. NovaDigm has completed a Phase 1b/2a clinical trial to evaluate NDV-3 in patients diagnosed with RVVC.1
Over the past 20 years, these Candida species have been found to cause an increasing number of life-threatening invasive infections. Nearly all of these invasive infections are due to current or recent hospitalizations. Invasive Candida infections are most often seen in patients who have taken broad spectrum antibiotics, have had a central venous catheter implanted or have prolonged hospitalization.2
Candida and fungi in general are very difficult to treat using therapeutic strategies. The similarity between fungal cells and human cells, which are both eukaryotic, makes the development of selective therapeutic agents more challenging than for bacterial pathogens. For this reason, therapeutic strategies for fungi tend to have higher toxicity than their bacterial counterparts. A result of this is that despite antifungal treatment, patients with invasive candidiasis (a systemic infection, including bloodstream infection) have a very high rate of mortality attributed to the infection (reported from 20-50%).3,4
Candida is the third most common cause of nosocomial bloodstream infections in U.S. hospitals.5 In a recent study of infected patients in 1,265 intensive care units across 75 countries, Candida was the third most prevalent pathogen at 17% of total infections (Staphylococcus aureus was first at 20%).6 Surveillance studies in Atlanta and Baltimore reported by the CDC estimated infection rates due to Candida of 13 and 26 per 100,000 person-years, respectively, with case fatality rates of 29% and 28%. These rates would correspond to 40,000 to 80,000 cases and 12,000 to 24,000 deaths per year in the United States. The study also showed increases in Candida infection rates since the last CDC surveillance studies, by 46% in Atlanta (over 16 years) and 8% in Baltimore (over 10 years).7
Due to the high incidence and high mortality associated with systemic Candida infections, a vaccine solution, such as NDV-3A, that teaches the body to mount a stronger immune response to Candida, would potentially be an effective way to reduce both the incidence of infection and mortality, ultimately having the potential to save thousands of lives every year. Results from two Phase 1 clinical trials in 200 healthy adults demonstrated that the NDV-3 vaccine was safe, well-tolerated and induced strong antibody and T-cell immune responses to the vaccine in healthy adults. Results from the most recent Phase 1b/2a study demonstrated that NDV-3A was safe and well tolerated and statistically significant measures of efficacy were observed in patients with RVVC.
- ClinicalTrials.gov Identifier: NCT01926028.
- Spellberg BJ and Edwards JE Jr., The pathophysiology and treatment of Candida sepsis. Curr. Infect. Dis. Rep 2002; 4:387–99.
- Gudlaugsson, O, Gillespie S, Lee K, Vande Berg K, Hu J, Messer S, Herwaldt L., Pfaller M, and Diekema D, Attributable mortality of nosocomial candidemia, revisited. Clin. Infect. Dis. 2003; 37:1172–1177.
- Morgan J, Meltzer MI, Plikaytis BD, Sofair AN, Huie-White S, Wilcox S, Harrision LH, Seaberg EC, Hajjeh RA and Teutsch S, Excess mortality, hospital stay and cost due to candidemia: a case-control study using data from population-based candidemia surveillance. Inf. Control Hosp. Epidemiol. 2005; 26: 540-47.
- Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP and Edmond MB, Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 2004; 39:309–17.
- Vincent J-L, Rello J, Marshall J, Silva E, Anzueto A, Martin C, Moreno R, Lipman J, Gomersall C, Sakr Y, Reinhardt K and the EPIC II Group of Investigators, JAMA 2009; 302:2323-9.
- Cleveland AA, Farley MM, Harrison LH, Stein B, Hollick R, Lockhart SR, Magill SS, Derado G, Park BJ and Chiller, TM, Changes in Incidence and Antifungal Drug Resistance in Candidemia: Results from Population-Based Laboratory Surveillance in Atlanta and Baltimore, 2008-2011. Clin. Infect. Dis. 2012; 55(10): 1352-61.