Moderna BA.4/BA.5 Targeting Bivalent Booster Met Primary Endpoint When Compared to Booster Dose

Both of Moderna’s bivalent Omicron-targeting booster candidates, mRNA-1273.214 and mRNA-1273.222, activated a superior antibody response compared to a booster dose of mRNA-1273 against Omicron BA.4/BA.5 in phase 2/3 clinical trials. Further, both bivalent vaccines also met non-inferiority immunogenicity criteria to the original strain.

"We are pleased to see that both of our bivalent booster vaccine candidates offer superior protection against Omicron BA.4/BA.5 variants compared to our original booster, which is encouraging given COVID-19 remains a leading cause of hospitalization and death globally," said Stéphane Bancel, Moderna's Chief Executive Officer, in a press release.

In the phase 2/3 study, a 50 µg booster dose of mRNA-1273.222 provoked a superior neutralizing antibody response against Omicron BA.4/BA.5 variants when compared to a 50 µg booster dose of mRNA-1273 in 511 previously vaccinated and boosted participants between the ages of 19 and 89 years.

During the trial, the participants received mRNA-1273.222 and mRNA-1273 approximately 9.5 months and 4.5 months after their prior vaccination. Further, pre-booster BA.4/BA.5 titers were similar between the mRNA-1273.222 and mRNA-1273 groups.

The Omicron BA.4/BA.5 geometric mean titer (GMT) ratios of mRNA-1273.222 versus mRNA-1273 were 5.11 and 6.29 for participants with and without SARS-CoV-2 infection pre-booster,

respectively. In all the participants, the GMT against Omicron BA.4/BA.5 was 4289, representing a 15.1-fold increase from pre-booster levels. For those without prior infection, the GMT was 2325, which represents a 26.4-fold increase; for those with prior infection, the GMT was 6965, representing a 9.8-fold increase from pre-booster levels. Additionally, these results were consistent between participants aged 65 years and older and those between the ages of 18 and 65 years.

“The superior response [of the bivalent booster] against Omicron persisted for at least 3 months after the mRNA-1273.214 booster,” Bancel said in the press release. "Our bivalent boosters also show, in research assays, neutralizing activity against BQ.1.1, an increasingly dominant emerging variant, confirming that updated vaccines have the potential to offer protection as the virus continues to evolve rapidly to escape our immunity."

Additionally, despite an approximately 5-fold drop in titers for BA.4/BA.5 in an analysis of approximately 40 participants using research assays, the bivalent vaccines continued to demonstrate a robust neutralizing activity against BQ.1.1.

In previously published data, a 50 µg booster dose of mRNA-1273.214 initiated a superior neutralizing antibody response against Omicron BA.1 and Omicron BA.4/BA.5 compared to the booster dose of mRNA-1273, with superiority lasting through at least 3 months. Participants in both groups received the booster dose approximately 4.5 months after prior vaccination.

Furthermore, adverse events with mRNA-1273.222 and mRNA-1273.214 were similar or lower than that of either a second or third dose of the original vaccine. No new safety concerns were identified after approximately 1 month and 3 months of follow-up, respectively.

REFERENCE

MODERNA'S BA.4/BA.5 targeting bivalent booster, mrna-1273.222, meets primary endpoint of superiority against omicron variants compared to booster dose of mrna-1273 in phase 2/3 clinical trial. Moderna. November 14, 2022. Accessed November 18, 2022. https://investors.modernatx.com/news/news-details/2022/Modernas-BA.4BA.5-Targeting-Bivalent-Booster-mRNA-1273.222-Meets-Primary-Endpoint-of-Superiority-Against-Omicron-Variants-Compared-to-Booster-Dose-of-mRNA-1273-in-Phase-23-Clinical-Trial/default.aspx