KING OF PRUSSIA, Pa. & SAN DIEGO– Global biotechnology leader CSL (ASX:CSL; USOTC:CSLLY) and Arcturus Therapeutics (Nasdaq: ARCT) today announced the results of a follow-up analysis of a Phase 3 study evaluating a booster dose of ARCT-154, the world’s first approved self-amplifying messenger RNA (sa-mRNA) COVID-19 vaccine, compared to a conventional mRNA COVID-19 vaccine. ARCT-154 was administered at one-sixth the dose of Comirnaty® (5 μg vs 30 μg, respectively).
The new analysis at 6 months post-vaccination shows that ARCT-154 induces a longer immune response as compared to Comirnaty for both the original Wuhan strain and Omicron BA.4/5 variant and an advantage in antibody persistence.
“These results further support sa-mRNA’s differentiating attribute to provide prolonged protection against COVID-19 at lower doses,” said Jonathan Edelman, M.D., Senior Vice President, Vaccines Innovation Unit, CSL. “Protecting the global public from viral respiratory diseases remains a top priority for us, and we look forward to continuing to collect and share data at the twelve-month post-booster mark.”
“This data, coupled with the initial Phase 3 results and approval in Japan late last year, show that this innovative vaccine technology has the potential to provide significant advancements over conventional mRNA vaccines including prolonged protection at lower doses,” said Pad Chivukula, Ph.D., Chief Scientific Officer of Arcturus Therapeutics.
ARCT-154 Six-Month Data Report
This randomized, double-blind, active-controlled study, conducted at 11 sites in Japan assessed the immunogenicity of ARCT-154 and Comirnaty® at one, three- and six-months post-booster. Participants who displayed seropositivity for SARS-CoV-2 N-protein on Days 1, 29, 91 or 181 were considered indicative of recent COVID-19 infection and therefore, were progressively excluded from the analysis, leaving 332 and 313 participants in ARCT-154 and Comirnaty® groups, respectively, eligible for inclusion at the six-month immunogenicity evaluation.
At baseline, participants in both groups had similar geometric mean titers (GMTs) surrogate virus neutralizing antibodies against Wuhan-Hu-1 strain (GMT ratio was 0.94 (95% CI 0.78-1.13)). One-month post-booster, the ARCT-154 group displayed a higher immune response with GMT of 5390 (95% CI 4899-5931, n = 378) compared to Comirnaty® group with GMT of 3738 (95% CI 3442-4060, n = 367), and a GMT ratio of 1.44 (95% CI 1.27–1.64).
Three months post-booster GMTs were 5928 (95% CI 5414–6491, n = 369) and 2899 (2648–3175, n = 356), with a higher GMT ratio of 2·04 (1·80–2·32). Day 91 titers were equal to or greater than Day 29 titers in 205 of 369 (55·6% [95% CI 50·3–60·7]) ARCT-154 recipients, but in only 108 of 356 (30·3% [25·6–35·4]) Comirnaty® recipients. Due to different rates of antibody waning, by Day 181 GMTs were 4119 (95% CI 3723–4557, n = 332) and 1861 (1667–2078, n= 313) in ARCT-154 and Comirnaty® groups, respectively, maintaining a GMT ratio of 2·21 (1·91–2·57) between vaccine groups. GMTs against Wuhan-Hu-1 remained numerically higher 180 days after ARCT-154 than those observed 28 days after the Comirnaty® booster.
The same pattern of superior immunogenicity and slower decline in Omicron BA.4/5 neutralizing antibodies was observed: GMTs were comparable at baseline (GMT ratio of 0.94 (95% CI 0.71-1.26), and increased to 2125 (95% CI 1841–2453) vs. 1624 (1418–1858) at Day 29 after ARCT-154 and Comirnaty®, then waned to 1892 (1646–2175) and 888 (764–1031), respectively, at Day 91. Between Days 29 and 91 titers were stable or increased in 128 of 369 (34·7% [95% CI 29·8–39·8]) ARCT-154 recipients, compared with 36 of 356 (10.1% [7·2–13·7]) in the Comirnaty® group. The difference in neutralizing activity against Omicron BA.4/5 was maintained to Day 181 when GMTs were 1119 (95% CI 960–1305) and 495 (413–595), with a GMT ratio of 2·26 (1·78–2·86) in favor of ARCT-154.
