NovaDigm's lead development candidate, NDV-31, is the first vaccine to provide preclinical "cross-kingdom" protection against both fungal and bacterial pathogens. In preclinical studies, the vaccine demonstrated protection against both vaginal and bloodstream infections due to the fungal pathogen Candida.2 NDV-3 also was protective in preclinical models for Staphylococcus aureus (S. aureus) skin and soft tissue and bloodstream infections.3,4
Results published from the first Phase 1 clinical trial in 40 healthy adults demonstrated that a single dose of the NDV-3 vaccine was safe, well-tolerated and induced strong antibody and T-cell immune responses.5 A second Phase 1 study in 160 healthy adults assessed dose levels, routes of administration and need for an aluminum-based adjuvant (often referred to as “alum”).6 Alum has a long track record of being a safe and effective adjuvant in a number of commercially available vaccines. The excellent results from these studies supported the Company’s initiation of a Phase 1b/2a clinical trial7 in patients diagnosed with recurrent vulvovaginal candidiasis (RVVC), a chronic condition that affects approximately seven million women in the United States.8
The Phase 1b/2a study of 188 women with RVVC met primary measures of safety, tolerability and immunogenicity and showed a statistically significant impact of the therapy vs placebo on the proportion of women who were recurrence-free at twelve months following a single dose of NDV-3A and an increase in time to first recurrence for those who continued to have symptoms.
- NDV-3 and NDV-3A are both formulations of a vaccine containing the N-terminal portion of the recombinant Als3 protein. NDV-3 was used during preclinical development and Phase 1 clinical studies and contains a histidine tag. NDV-3A, which does not contain a histidine tag, is the formulation that NovaDigm is moving forwards into later stage clinical development. NDV-3 and NDV-3A were compared during the Phase 1b/2a clinical study and their safety, tolerability and immunogenicity was found to be equivalent.
- Spellberg BJ, Ibrahim AS, Avanesian V, Fu Y, Myers C, Phan QT, Filler SG, Yeaman MR and Edwards JE Jr., Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J. Inf. Dis. 2006; 194:256-60.
- Spellberg BJ, Ibrahim AS, Yeaman MR, Lin L, Fu Y, Avanesian V, Bayer AS, Filler SG, Lipke P, Otoo H, and Edwards JE Jr., The antifungal vaccine derived from the recombinant N terminus of Als3 protects mice against the bacterium Staphylococcus aureus. Infect. Immun. 2008; 76:4574-580.
- Yeaman MR, Filler SG, Chaili S, Barr K, Wang H, Kupferwasser D, Hennessey JP Jr., Fu Y, Schmidt CS, Edwards JE Jr., Xiong YQ and Ibrahim AS, Mechanisms of NDV-3 Vaccine efficacy in MRSA skin versus invasive infection. PNAS 2014; www.pnas.org/cgi/doi/10.1073/pnas.1415610111.
- Schmidt CS, White CJ, Ibrahim AS, Filler SG, Fu Y, Yea.man MR, Edwards JE Jr., Hennessey JP Jr., NDV-3, a recombinant alum-adjuvanted vaccine for Candida and Staphylococcus aureus, is safe and immunogenic in healthy adults. Vaccine 2012; 30:7594-7600.
- ClinicalTrials.gov Identifier: NCT01447407.
- ClinicalTrials.gov Identifier: NCT01926028.
- L.E.K. Consulting primary research on vulvovaginal candidiasis conducted in 2,400 US women, 2011.