Periodic Reporting for period 2 - ETVAX (ETVAX – the first oral vaccine for protection against traveller’s diarrhoea caused by ETEC)
Berichtszeitraum: 2018-09-01 bis 2020-05-31
The most common cause of Travellers’ Diarrhoea (TD) is EnteroToxigenic E. coli bacteria (ETEC). TD is the most common illness affecting travellers in the developing regions. Currently, there is no approved vaccine for preventing TD. Travellers are recommended to use antibiotics such as Rifaximin or the cholera vaccine Dukoral to prevent TD. In business terms, there exists a strong business opportunity in developing and commercializing an effective and safe ETEC vaccine. Scandinavian Biopharma is the first company positioned to capture this opportunity.
Scandinavian Biopharma is developing ETVAX – an oral vaccine against traveller’s diarrhoea caused by enterotoxigenic E. coli bacteria (ETEC). ETVAX has a strong potential to be the first vaccine with a full ETEC indication. The development of the vaccine is run in collaboration with the world’s most prominent experts in ETEC vaccine research (e.g. professor Ann-Mari Svennerholm and Professor Jan Holmgren, Göteborg University and Dr August Bourgeois, PATH.
The Phase IIb study at the core of the project will allow Scandinavian Biopharma to progress towards commercialization of ETVAX.
Scandinavian Biopharma is developing ETVAX – an oral vaccine against traveller’s diarrhoea caused by enterotoxigenic E. coli bacteria (ETEC). ETVAX has a strong potential to be the first vaccine with a full ETEC indication. The development of the vaccine is run in collaboration with the world’s most prominent experts in ETEC vaccine research (e.g. professor Ann-Mari Svennerholm and Professor Jan Holmgren, Göteborg University and Dr August Bourgeois, PATH.
The Phase IIb study at the core of the project will allow Scandinavian Biopharma to progress towards commercialization of ETVAX.
The project has progressed according to plan, with some delay. The study started in July 2017 and last patient out was in April 2019, 729 travellers have been vaccinated in Finland and travelled to Grand Popo in Benin to participate in the study. As the project is complex and includes organizations from several different countries, Scandinavian Biopharma invests a lot of effort into co-ordination, communication and dissemination activities. During the latter part of the study, there was some time delays: a) FIMEA the Finnish pharmaceutical agency conducted an audit that the project team successfully responded to b) The Finish CRO Medfiles had to change data management supplier in Finland at a very late stage c) The covid 19 pandemic in Finland caused a standstill in the close-out visits and the last reports of the study.
The project has attracted major media attention as well as scientific attention and World Health Organization is following the project closely.
The primary results confirm the excellent safety and overall positive immunogenicity of ETVAX®. While not reaching our protective efficacy goal of 70%, we are pleased to see a significant protective efficacy (PE = 56%) against all severe diarrhea, regardless of pathogen, most likely because ETEC was found in 75% of all severe diarrhea cases.
Despite the higher than expected TD attack rate and severity of ETEC-associated disease, ETVAX® provided significant protection. The PE against moderate-to-severe disease among vaccine responders (≥4-fold seroconversion to LTB) against any ETEC, and allowing for concomitant presence of EAEC, EPEC, EIEC/Shigella, Salmonella sp., Campylobacter sp., and parasites, was 52% (p=0.006; 95% CI=18-72%), representing 25% of all TD. When disregarding vaccine immune response, the protection remained significant (PE=41%, p=0.02; 95% CI=7-63%). Mixed infection with ETEC of another toxin and/or CF phenotype proved surprisingly common (18% of VPO ETEC cases) and decreased the measured protective capacity slightly. Overall, the PE against diarrhea of any cause (including viral pathogens) affecting daily activities increased progressively with increasing severity of disease, so that among vaccine responders with ≥16 loose stools in 24 hours the PE was 56% (p=0.025 CI= 9-83%) and disregarding the vaccine immune response it was 43% (p=0.05). This represents 22% of all TD.
The project has attracted major media attention as well as scientific attention and World Health Organization is following the project closely.
The primary results confirm the excellent safety and overall positive immunogenicity of ETVAX®. While not reaching our protective efficacy goal of 70%, we are pleased to see a significant protective efficacy (PE = 56%) against all severe diarrhea, regardless of pathogen, most likely because ETEC was found in 75% of all severe diarrhea cases.
Despite the higher than expected TD attack rate and severity of ETEC-associated disease, ETVAX® provided significant protection. The PE against moderate-to-severe disease among vaccine responders (≥4-fold seroconversion to LTB) against any ETEC, and allowing for concomitant presence of EAEC, EPEC, EIEC/Shigella, Salmonella sp., Campylobacter sp., and parasites, was 52% (p=0.006; 95% CI=18-72%), representing 25% of all TD. When disregarding vaccine immune response, the protection remained significant (PE=41%, p=0.02; 95% CI=7-63%). Mixed infection with ETEC of another toxin and/or CF phenotype proved surprisingly common (18% of VPO ETEC cases) and decreased the measured protective capacity slightly. Overall, the PE against diarrhea of any cause (including viral pathogens) affecting daily activities increased progressively with increasing severity of disease, so that among vaccine responders with ≥16 loose stools in 24 hours the PE was 56% (p=0.025 CI= 9-83%) and disregarding the vaccine immune response it was 43% (p=0.05). This represents 22% of all TD.
The project delivers an ultimate EU added value by offering the first ETEC vaccine with proven immunogenicity, safety and efficacy. From the scientific perspective, this means that the project fills the gap in the vaccine research on the EU and global level as no other efficient methods for prevention of TD have been proposed on the market to date. The introduction of ETVAX will ultimately decrease number of TD cases among travellers as shown by our phase 2b efficacy data. Furthermore, use of antibiotics among vaccine rescipients was significantly lower than among placebo recipients. The vaccine has potential to decrease number of patients with irritable bowel syndrome or other chronic diseases connected to TD, as well as decrease healthcare costs and productivity losses on the EU level. If successfully validated and accepted by regulatory bodies, ETVAX will take Scandinavian Biopharma to a new level of competitiveness and growth.