At the end of November, Japan's Ministry of Health, Labor and Welfare (MHLW) granted approval for ARCT-154, a self-amplifying messenger RNA (sa-mRNA) COVID-19 vaccine for initial vaccination and booster for adults 18 years and older. Arcturus Therapeutics is in an exclusive partnership with CSL Seqirus, CSL’s vaccine subsidiary, and is manufacturing the ARCT-154 vaccine. The companies are developing novel mRNA vaccines against COVID-19 and influenza.1
"Today's approval marks a historic and exciting milestone as the first sa-mRNA vaccine in the world to be registered, and supports CSL's promise to protect global public health," Jonathan Edelman, MD, senior vice president, Vaccines Innovation Unit, CSL, said in a statement. "We are committed to working with health authorities around the world to ensure this important vaccine technology will be available to people at risk for COVID-19." 1
The approval is based on positive clinical data from several studies, which included an ongoing 16,000 subject efficacy study performed in Vietnam as well as study from booster trial. In previous reporting from Contagion, topline data from the booster study demonstrated higher immunogenicity results and a favorable safety profile compared to a standard mRNA COVID-19 vaccine comparator.
What You Need to Know
In November, Japan's Ministry of Health, Labor and Welfare (MHLW) granted approval for ARCT-154, a self-amplifying mRNA (sa-mRNA) COVID-19 vaccine.
Arcturus Therapeutics is collaborating with CSL Seqirus, CSL’s vaccine subsidiary, to develop novel mRNA vaccines targeting COVID-19 and influenza.
ARCT-154 belongs to the self-amplifying mRNA platform, which differs from traditional mRNA vaccines.
The booster study was a phase 1/2 randomized, observer-blind trial conducted in both the US and Singapore, and included 36 adult participants who were previously immunized with approved COVID-19 mRNA vaccines as a primary series.
Participants were randomized 1:1:1 to receive one booster dose on day 1 of either the ARCT-021, ARCT-154, or ARCT-165 vaccines, all of which encode the SARS-CoV-2 full-length S glycoprotein of, respectively, the ancestral strain in native conformation, a prefusion-stabilized B1 variant including the D614G mutation, or the Beta variant. Immunogenicity was assessed as neutralizing antibody titers against the SARS-CoV-2 D614G strain, and a panel of variants measured by pseudoviral microneutralization assay on Days 1, 15, 29, 91, 181, 271, and 366.
All 3 vaccines induced robust neutralizing immune response against the D614G variant at Day 29 with geometric mean fold rises (GMFR) from pre-booster levels of 20.0, 36.7 and 23.5 after ARCT-021, ARCT-154, and ARCT-165, respectively. ARCT-154, a leading candidate, induced a broad, cross-neutralizing immune response, which persisted up to one-year post-booster with no further boosting. Similar trends were observed for other variants including Beta, Delta, Omicron BA1, Omicron BA2, and Omicron BA4/5. Additional exploratory testing confirmed cross-neutralization against emergent BQ11 and XBB15 Omicron sub-lineages with GMFRs of 12.8 and 3.4, respectively, at Day 29 post-booster.
The sa-mRNA Platform
The Messenger RNA (mRNA) vaccine platform protects against infectious diseases by instructing cells in the body to make a specific protein, stimulating the immune response, and leaving a blueprint to recognize and fight future infection. However, sa-mRNA makes copies of the mRNA which generates the production of more protein compared to an equivalent amount of mRNA in a vaccine. The companies report the technology has the potential to create more potent cellular immune responses and increase duration of protection, while using considerably lower doses of mRNA.1
1. Japan's Ministry of Health, Labour and Welfare Approves CSL and Arcturus Therapeutics' ARCT-154, the first Self-Amplifying mRNA vaccine approved for COVID in adults. Press release. November 28, 2023. https://www.prnewswire.com/news-releases/japans-ministry-of-health-labour-and-welfare-approves-csl-and-arcturus-therapeutics-arct-154-the-first-self-amplifying-mrna-vaccine-approved-for-covid-in-adults-301999193.html