Vaxart is still looking a little queasy. The biotech delivered mixed data on its oral monovalent norovirus vaccine candidate, with the failure to cut acute gastroenteritis in the challenge study ensuring a muted response from investors despite successes on other endpoints.
For the midphase challenge study, investigators randomized people to receive VXA-G1.1-NN, an adenoviral-vector based norovirus vaccine, or placebo. One month after vaccination, the subjects entered an isolation ward and were exposed to the norovirus strain targeted by the vaccine.
One primary endpoint looked at the rate of acute gastroenteritis by monitoring subjects for symptoms such as diarrhea, vomiting and nausea in the week after they were exposed to the virus. VXA-G1.1-NN failed to perform significantly better than placebo on a composite endpoint of norovirus gastroenteritis, with 44.7% of participants suffering symptoms in the treatment group compared to 56.9% in the control.
Talking on a conference call with investors to discuss the results, James Cummings, M.D., chief medical officer at Vaxart, predicted that the vaccine may perform better outside of the artificial challenge environment.
“We use lots of copies of virus to ensure a high infection rate. In nature, 10 to 15 copies of virus is generally enough to give certain susceptible individuals disease. Field efficacy generally goes up, because the amount of inoculum that is causing disease that will be seen in the field is far lower than what is seen in the challenge study,” Cummings said. “My projection is that we would see an improvement in the decrease of [acute gastroenteritis] with our vaccine.”
The potential for the vaccine to perform better in field studies was one cause for optimism identified by Vaxart. Infection data were another positive. In the 76 recipients of VXA-G1.1-NN, Vaxart saw a norovirus infection rate of 47.9%. The infection rate was lower than the 81.5% figure seen in the control group, resulting in a statistically significantly 29% relative risk reduction.
Vaxart sees the finding as evidence that its vaccine can reduce viral transmission. “The 29% rate of infection certainly decreases the chance of transmitting virus to others, and I would fold into that the decrease in viral shedding as well,” Cummings said. “That may also decrease transmission in those close contact environments. That’s, to me, the two-pronged benefit of those findings.”
The company is continuing to analyze the data to inform a larger phase 2b trial and identify ways to cut the size and duration of a planned registration trial. Vaxart is also working on a bivalent vaccine that may provide broader protection. Investors were largely unmoved by the update, sending the biotech’s stock up 1.7% to 81 cents in premarket trading.