Novadigm Therapeutics is pioneering new ground with a single asset — a vaccine against two sepsis-causing microbes: Candida, a fungus, and Staph aureus, a bacteria. After infectious disease specialists at UCLA found the surface protein common to the fungus and sepsis-causing bacteria, some of them started up Novadigm to develop the vaccine in its NDV3 (Als3 antigen) program. Besides the hospital-infection market, the vaccine could reach a much larger potential market in infection-prone patients who are immune-compromised, on antibiotics, or who have hard-to-treat conditions like recurrent vulvovaginal candidiasis. Novadigm’s recombinant vaccine showed impressive immune response in a Phase 1 trial.
• A second Phase 1 study in 160 healthy adults demonstrated that a single dose of NDV-3 with or without alum adjuvant was safe, well-tolerated and induced strong antibody and T-cell immune responses. This type of with-and-without-adjuvant comparison now seems to be routinely requested by the FDA. These results from the Phase 1 data should allow the company to proceed with a single “adjuvant-free” formulation into Phase 2 studies rather than bringing two formulations into later-stage studies.
• The second Phase 1 study also showed strong vaginal antibody responses to NDV-3, which may be important in preventing vaginal yeast infections caused by Candida albicans, which is being planned as the company’s first Phase 2 efficacy study.
WHAT’S AT STAKE
It really did sound astounding the first time I heard that Novadigm was developing the world’s first cross-kingdom vaccine. Staph aureus is a member of the bacteria kingdom. But now I read that fungi, which are widely associated with plants and mushrooms, have more in common with the animals on the cellular level, all being eukaryotes. Still, my amazement is just as strong, whichever kingdom or species Candida and Staph aureus represent. Between them, the two microbes cause one of most fearsome threats to hospital patients (and others). For a vaccine to counter them both — and thus prevent bloodstream infections and resulting sepsis — with a single antigen would be a miraculous achievement.
Sepsis is the host inflammatory response to bloodstream infections by bacteria or fungi. The vaccine has the potential to prevent serious bloodstream infections and in turn prevent sepsis, the host response. Thus Novadigm doesn’t regard it as an “anti-sepsis” vaccine, although “it may prevent sepsis in some cases” by targeting the microbes far “upstream” of the sepsis response.
As I wrote a few months back, Novadigm still faces a long slog in moving its first product through mid- and late-stage trials. But that’s only part of the story. The context is the unexplored territory it faces in making the trek, specifically with vaccine against multiple healthcare-associated infections, as a small life science company.
This may be one area that Big Pharma does not want to rush into at too early a stage. Pfizer, GSK, and Novartis all have clinical-stage Staph aureus vaccine programs. Merck had one but terminated development last year after failing a Phase 2/3 study in 8,000 elective surgery patients. Novartis is the only Big Pharma with a publicly-disclosed Candida vaccine program. I recently profiled Janssen Biotech, a descendent of Centocor, which once barely survived a failed foray into the fickle field of sepsis. Novadigm appears in no hurry to sign a major deal before its vaccine passes an upcoming Phase 2 trial. But when it does, it seems ready to sell the whole shebang. The big question: Will the big vaccine players like Merck, Sanofi, and Pfizer wait it out to see efficacy data before snatching the prize — or will one of them swoop in sooner as the partner willing to share the risk?