Japan Approves Updated Self-Amplifying mRNA COVID-19 Vaccine

Japan has approved the CSL and Arcturus Therapeutics' Updated self-amplifying (SA) mRNA COVID-19 Vaccine, ARCT-154 (Kostaive). The updated vaccine is targeted to protect against the JN1 lineage of omicron subvariants for adults 18 years of age and older. "We are pleased to receive the updated approval from Japan's Ministry of Health, Labor and Welfare, and remain on track to distribute Kostaive in time for the October COVID-19 vaccination campaign," Emmanuelle Lecomte-Brisset, senior vice president and head of Global Regulatory Affairs, CSL, said in a statement. "We look forward to introducing Kostaive in Japan as a safe, tolerable and more durable option in protecting against COVID-19."

This became the world’s first such vaccine platform approved when Japan gave it the nod last November. Arcturus Therapeutics is in an exclusive partnership with CSL Seqirus, CSL’s vaccine subsidiary.

CSL's exclusive partner in Japan, Meiji Seika Pharma, will begin distributing the updated vaccine in time for the October COVID-19 vaccination campaign. Back in May, a Japanese health ministry panel recommended that COVID-19 vaccines be updated to target the JN1 variant 2024/2025 national immunization program. This aligns with recent recommendations from the World Health Organization.

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.²

Previous Data

Back in May, data was published from studies demonstrating the vaccine's high efficacy protection against the omicron variant BA 4/5.

The observer-blind, randomized, controlled phase 1, 2, 3a and 3b integrated study, adults ≥18 years old receive two 5 μg doses of ARCT-154 or saline placebo 28 days apart. Phase 2/3a/3b participants were stratified by age (< 60 or ≥ 60 years of age) and by risk of severe COVID-19 prior to being randomized 3:1 (phase 1/2/3a) or 1:1 (phase 3b) to vaccine or placebo groups.³

The primary endpoints were vaccine efficacy up to 2 months after dose 2, reactogenicity within up to 7 days of each dose, safety within up to 28 days after each dose, and immunogenicity measured 28 days after each dose From August 15 to January 12, 2023, 1001 participants were randomized (748 ARCT-154 and 253 placebo) in the integrated phase 1/2/3a study, and 16,100 participants (8,056 ARCT-154 and 8,044 placebo) in the phase 3b study.³

In the phase 1/2/3a studies, ARCT-154 was safe and well tolerated. Most solicited adverse events were mild or moderate and resolved quickly, and rates of related or severe unsolicited adverse events were similar in the ARCT-154 and placebo groups. The phase 3b study confirmed these observations.³

Four weeks after the second ARCT-154 dose in phase 3b, the neutralizing antibody seroconversion rate was 94.1% (95% CI: 92•1–95•8). There were 640 confirmed, protocol-defined COVID-19 cases, mainly of the Delta variant, that were determined to be eligible for analysis, including 43 severe cases and 10 deaths attributed to COVID-19.³

ARCT-154 absolute efficacy was 56.6% (95% CI: 48.7– 63.3) against any COVID-19, 95•3% (80.5–98.9) against severe COVID-19 and 86.5% (-7.4–98.3) against death due to COVID-19.³

Efficacy against severe COVID-19 was 100% in healthy 18-59-year-olds and 91.9% (37.9-98.9) in participants in that age group with underlying co-morbidities, which put them at risk for severe disease.³

In adults aged 60 years or older, efficacy was 54.3% (28.2–70.9) against COVID-19 of any severity and 94.4% (58.2–99.3) against severe COVID-19.³

"We are pleased that our sa-mRNA technology will be available to vaccinate people in Japan against COVID-19, which remains an ongoing risk to public health around the world," Arcturus Therapeutics CEO Joseph Payne, said in a statement. "We look forward to continuing to work with CSL and regulators to explore the development of Kostaive in additional countries."¹

References
1. Japan's Ministry of Health, Labor and Welfare Approves CSL and Arcturus Therapeutics' Updated Self-amplifying mRNA COVID-19 Vaccine for Protection against JN.1 Strain, to be Distributed in Japan by Meiji Seika Pharm. CSL press statement. September 13, 2024. Accessed September 17, 2024. https://www.prnewswire.com/news-releases/japans-ministry-of-health-labor-and-welfare-approves-csl-and-arcturus-therapeutics-updated-self-amplifying-mrna-covid-19-vaccine-for-protection-against-jn1-strain-to-be-distributed-in-japan-by-meiji-seika-pharma-302247674.html

2. 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. Accessed September 17, 2024. 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

3. Nature Communications Publishes Pivotal Data Demonstrating Efficacy and Tolerability of CSL and Arcturus Therapeutics' COVID-19 Vaccine. CSL news statement. May 20, 2024. Accessed September 17, 2024.
https://www.prnewswire.com/news-releases/nature-communications-publishes-pivotal-data-demonstrating-efficacy-and-tolerability-of-csl-and-arcturus-therapeutics-covid-19-vaccine-302149979.html