A novel oral vaccine, ETVAX, has demonstrated its potential to reduce paediatric cases of moderate-to-severe enterotoxigenic E. coli (ETEC)-triggered diarrhoea by up to 80.6% in a Phase IIb study.
This EDCTP2-funded trial (PACTR20201081921856), which was coordinated by Scandinavian Biopharma in Gambia, enrolled 4,936 children aged six to 18 months, with each participant randomised to receive three doses of either ETVAX or placebo at days 1, 15, and 90 of the study. The trial’s primary endpoint measured ETVAX’s efficacy against ETEC-positive diarrhoea in children not co-infected with other pathogens like rotavirus, norovirus, Shigella or Cryptosporidium in the per-protocol population.
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While ETVAX did not meet the study’s primary endpoint, demonstrating an efficacy rate of 26.6% (p=0.43), the vaccine only narrowly missed out on a statistically significant result when its impact against ETEC was measured regardless of co-pathogens. The efficacy in this scenario stood at 48.2% (p=0.053).
Despite its primary endpoint miss, ETVAX did display promise based on secondary and exploratory endpoints, with the treatment demonstrating 80.6% effectiveness (p=0.0092) in children who were not infected with certain intestinal parasites.
This study also highlighted the importance of early dosing with ETVAX, as 67.8% of children who started receiving a course of the vaccine before the age of nine months were protected against ETEC-positive diarrhoea.
The vaccine’s safety profile was also comparable to placebo, with serious adverse events (SAEs) occurring in 1% (24) and 1.3% (32) of children in the ETVAX and placebo groups, respectively. None of these SAEs were related to the vaccine.
The European & Developing Countries Clinical Trials Partnership, or EDCTP, is a collaborative programme between European and African countries. The scheme is designed to accelerate the development of new or improved medicines within the field of infectious disease by funding clinical research.
A race to develop the first ETEC vaccine
According to Thomas Wierzba, corresponding author of the Lancet paper summarising the trial, this is the first time an oral ETEC vaccine has shown potential to “offer real protection in a high-burden, low-income setting”.
Following the generally positive results obtained from this Phase IIb study, the European Medicines Agency (EMA) has given developers the greenlight to take ETVAX to a pivotal Phase III trial, which will test the vaccine’s consistency across different populations.
If ETVAX were to secure regulatory approval, it could become the first vaccine available to protect against ETEC-prompted diarrhoea. Currently, epidemiologists estimate that ETEC is responsible for an estimated 42,000 deaths per year.
The vaccine also diminished the overall prevalence of moderate-to-severe diarrhoea of all causes by 21% at the two-year mark, meaning the EDCTP3 hopes that ETVAX will become an important addition to the all-cause diarrhoea treatment arsenal – particularly in low-income areas.
If approved, ETVAX would join similar vaccines like MSD’s RotaTeq and GSK’s Rotarix within the preventative armamentarium, which are approved for protection against rotaviral infections that commonly result in diarrhoea. UNICEF commonly provides children in low-to-middle income countries with both of these vaccines.
Meanwhile, Moderna is also evaluating the potential of its trivalent, mRNA-based norovirus vaccine, mRNA-1403, in a Phase III trial, which began dosing in 2024.
