Scandinavian Biopharma reports successful results of the oral, inactivated ETEC vaccine candidate ETVAX® against enterotoxigenic E. coli diarrhoea in a placebo-controlled phase I/II study in infants and children from 6 months to 5 years of age in Bangladesh
The successful results of the Phase I/II study in Dhaka, Bangladesh, are now published in The Lancet Infectious Diseases.
All predefined primary endpoints for the study were achieved and exceeded, showing that the vaccine candidate was safe and broadly immunogenic, stimulating immune responses to all key vaccine components. Only a few mild to moderate adverse reactions were observed among participants; while the vaccine induced impressive serum and intestinal immune responses in young children and infants, with 80–100% of children 2–5 years of age and 50–80% of infants 6–11 months of age responding to all key vaccine antigens. Giving the vaccine together with an adjuvant enhanced the magnitude, breadth and kinetics of the intestinal immune responses in infants. Results are presented in this week´s issue of The Lancet Infectious Diseases.
Enterotoxigenic E. coli (ETEC) bacteria are a primary cause of diarrhoea, leading to substantial illness and death in children in low- and middle-income countries (LMICs) as well as in travellers to LMICs. Currently there is no ETEC vaccine available on the market for use in either children or travellers to ETEC high-risk areas, and ETEC vaccine development is a World Health Organization priority.
“The promising results have a strong clinical relevance and indicate that an effective ETEC vaccine for infants and children in LMICs, who are most at-risk of morbidity and mortality due to ETEC, may be within reach. The strong immune responses in the young cohorts suggest that it would be possible to initiate vaccinations from an early age, before most of the children risks getting infected by ETEC for the first time” says Professor Ann-Mari Svennerholm, University of Gothenburg.
The vaccine candidate ETVAX® consists of inactivated E. coli bacteria expressing high levels of protective antigens and the ETEC-based B subunit protein LCTBA. This clinical study examined the administration of ETVAX®, given alone or together with different doses of an adjuvant, double-mutant heat-labile toxin (dmLT), to assess the vaccine’s safety and immunogenicity in 450 children. Descending age-groups of children 2–5 years, 1–2 years and 6–11 months were given two doses of vaccine in one of three fractionated doses levels (i.e., 1/8, 1/4 and 1/2) of a full adult dose with or without different doses (2.5–10 µg) of the dmLT adjuvant or buffer alone (placebo) as a drink two weeks apart in a double-blind manner. In addition to safety analyses, immune responses were determined by measuring the amount of antibodies produced in the intestine (faeces) as well as antibodies secreted by lymphocytes circulating in blood to the intestine.
The study was conducted at International Centre for Diarrhoeal Disease Research (icddr,b) in Dhaka, Bangladesh, as a collaborative effort between the Sahlgrenska Academy at University of Gothenburg, icddr,b, Scandinavian Biopharma, and the non-profit global health organization, PATH. The results confirm and extend the promising data previously reported from ETVAX® trials in Swedish and Bangladeshi adults. Based on the results of this trial, a late phase African paediatric development program was initiated in April 2019 and funded by European and Developing Countries Clinical Trials Partnership (EDCTP) with EUR 7,4 million. The program consists of a Phase I trial in Zambia including 250 participants down to 6 months of age, and a Phase IIb study in The Gambia including 5 000 children. The objectives for the African paediatric development program are to further test safety, immunogenicity and to estimate protective efficacy of ETVAX®.
ETVAX® is the registered trademark of Scandinavian Biopharma’s vaccine candidate against diarrheal disease caused by ETEC. ETVAX® is currently in Phase IIb clinical trials to evaluate safety and estimate the protective efficacy in 743 Finnish travellers to Benin. The study will be unblinded Q1 2020.
ETVAX® is the only ETEC vaccine in late phase development and is judged as the most advanced ETEC vaccine project. The strong immunogenicity and safety data clearly distinguish ETVAX® from other vaccine candidates that are under development against ETEC induced diarrhoea.
Successful development of this vaccine will address an unmet medical need of children in low-middle income countries as well as in travellers. Currently there is no ETEC vaccine available on the market for use in either children or travellers in ETEC high-risk areas, and ETEC vaccine development is a World Health Organization (WHO) priority.