The trials in Vietnam – conducted when Delta and Omicron variants were dominant in the country – showed 95% efficacy overall for prevention of severe COVID-19.
The vaccine also showed 55% efficacy overall for preventing symptomatic disease.
Having met its primary efficacy endpoint in the Phase 3 study, the candidate will now advance into a booster trial in major markets.
Phase 3 data
The ongoing Phase 1/2/3 registrational study, sponsored by Arcturus’ collaborator Vinbiocare Biotechnology Joint Stock Company, enrolled over 19,000 adults in Vietnam, including individuals at higher risk of severe complications of COVID-19 disease.
The Phase 3 placebo-controlled vaccine efficacy portion of this study enrolled more than 16,000 participants.
The study met its primary endpoint of prevention of virologically confirmed COVID-19 disease. In an analysis of COVID-19 cases accrued between 7 days and 56 days after completion of a two-dose vaccination series, two 5-mcg doses of ARCT-154 demonstrated 55% vaccine efficacy for protection against COVID-19. The cases of COVID-19 disease in the study participants were detected in parallel with a SARS-CoV-2 outbreak in Vietnam in December 2021 to February 2022 where the Delta and Omicron were dominant.
The key secondary endpoint of severe COVID-19 disease (including COVID-19 related deaths) was analyzed and included 43 severe cases in the analysis. Forty-one cases occurred in the placebo group and 2 occurred in the ARCT-154 vaccinated group, demonstrating point estimate of vaccine efficacy of 95% against severe (including fatal) COVID-19 disease.
Nine COVID-19 related deaths were reported in the placebo group and 1 in the ARCT-154 vaccinated group. The single death in the ARCT-154 vaccination arm occurred in an older age group participant who was also at increased risk of severe COVID-19.
A review of safety data from over 17,000 participants enrolled in the Phase 1, 2 and 3 portions of the study (through one month after second dose of ARCT-154) showed the incidence of unsolicited adverse events in the ARCT-154 group and placebo group were comparable. The companies highlight that no cases of myocarditis or pericarditis have been reported; although they acknowledge the study is not large enough to reliably observe these events given their extremely rare frequency of occurrence.
“We are very pleased with these results, and to see ARCT-154 providing protection against symptomatic COVID-19 and almost complete protection against severe disease in a placebo-controlled vaccine efficacy study. This represents a key milestone for the Company and provides significant clinical validation of our STARR platform. We believe self-amplifying mRNA combined with our LUNAR delivery technology will create a path to better mRNA medicines,” said Joseph Payne, President and CEO of Arcturus Therapeutics. “We are grateful to our collaborator Vinbiocare and to Vietstar, a leading CRO in Vietnam, for their extraordinary effort and efficiency in the sponsorship and analysis of this trial. We are also thankful to the study participants, investigators and clinical trial sites for their invaluable contributions to the study.”
Arcturus is now advancing ARCT-154 (5 mcg) toward a pivotal booster study which will involve approximately 2,400 participants. A clinical research organization to conduct the trial has been engaged and the company has received feedback from several regulatory agencies, including the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) on the trial design.