Investigational COVID-19 Vaccine Shows Non-Inferior Efficacy vs. Spikevax in Phase III Trial

Image credit: rost9 | stock.adobe.com

Findings from the Phase III NextCOVE (NCT05815498) trial of Moderna’s mRNA-1283 showed the next-generation, investigational SARS-CoV-2 vaccine achieved the primary efficacy endpoint of non-inferiorty vs. Spikevax (mRNA-1273) in preventing COVID-19. Additionally, the trial demonstrated superior efficacy with mRNA-1283 in individuals aged 18 years and older compared to Spikevax, showing a consistent trend among a subset of patients aged 65 years and older, according to the investigators.¹

"We are very pleased that mRNA-1283 has now met its primary vaccine efficacy endpoint in Phase III, and showed higher efficacy in adults compared to Spikevax," said Stéphane Bancel, chief executive officer of Moderna. "With five vaccine programs that have achieved positive Phase III results, Moderna's platform is consistently demonstrating its ability to address significant unmet needs in public health."¹

mRNA-1283 is an mRNA-LNP vaccine that encodes for a chimeric protein (NTD-RBD-HATM) comprised of the SARS-CoV-2 S protein NTD and RBD, which are attached by a flexible peptide linker and anchored to a 23-amino acid transmembrane domain from influenza hemagglutinin.²

The randomized, observer-blind, active-controlled NextCOVE trial enrolled approximately 11,400 individuals aged 12 years and older. Participants were randomly assigned to receive a single intramuscular injection of either mRNA-1283 or mRNA-1273.³

Results from the trial released in March show that compared to mRNA-1273, mRNA-1283 achieved a greater immune response against both the Omicron BA.4/BA.5 COVID-19 variant and the original strains of SARS-CoV-2.⁴ The elevated immune response was most acutely observed in individuals aged over 65 years, which is a population with the greatest risk of severe outcomes from COVID-19. The most frequent local adverse event (AE) was injection site pain, with headache, fatigue, myalgia, and chills being the common solicited systemic AEs.

Previously announced interim findings from a Phase I randomized clinical trial (NCT04813796) of mRNA-1283 demonstrated that across the 10 µg, 30 µg, and 100 µg dose levels administered on a two-dose schedule 28 days apart, mRNA-1283 was generally safe and produced robust immune responses comparable to mRNA-1273 at a dose of 100 µg. The lowest administered dose level of mRNA-1293 at 10 µg showed the most favorable tolerability profile, with robust nAb and bAb responses to SARS-CoV-2 after the second dose, which was similar to mRNA-1273. Investigators stated that the results suggest a two-dose regimen of mRNA-1283 at a lower dose level may produce similar efficacy to mRNA-1273.

“In conclusion, these preliminary findings support the continued evaluation of mRNA-1283, a next-generation SARS-CoV-2 vaccine,” the investigators wrote. “All dose levels of mRNA-1283 administered via a 2-dose regimen, 28 days apart, were generally safe in healthy adults aged 18–55 years, with the lowest dose level (10 µg) inducing comparable immunogenicity to the approved mRNA-1273 100 µg regimen. Clinical evaluation of mRNA-1283 is ongoing to assess the applicability of booster doses at lower dose levels and immune responses against other SARS-CoV-2 variants.”³

Moderna said it present the latest data for mRNA-1283 at an upcoming conference and will discuss next steps for the program with regulatory authorities.¹

References

1. Moderna Announces Positive Phase 3 Efficacy Data for mRNA-1283, the Company’s Next Generation COVID-19 Vaccine. News release. Moderna. June 13, 2024. Accessed June 13, 2024. https://investors.modernatx.com/news/news-details/2024/Moderna-Announces-Positive-Phase-3-Efficacy-Data-for-mRNA-1283-the-Companys-Next-Generation-COVID-19-Vaccine/default.aspx

2. Clinicaltrials.gov. A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 (NextCOVE). Website. Qpril 18, 2023. Accessed June 13, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05815498

3. Patrick Yassini, Mark Hutchens, Yamuna D. Paila, Lorraine Schoch, Anne Aunins, Uma Siangphoe & Robert Paris (2023) Interim analysis of a phase 1 randomized clinical trial on the safety and immunogenicity of the mRNA-1283 SARS-CoV-2 vaccine in adults, Human Vaccines & Immunotherapeutics, 19:1, DOI: 10.1080/21645515.2023.2190690.

4. Moderna Achieves Positive Interim Results from Phase 3 Trial of Next-Generation COVID-19 Vaccine. Moderna. News release. March 26, 2024. Accessed June 13, 2024. https://investors.modernatx.com/news/news-details/2024/Moderna-Achieves-Positive-Interim-Results-from-Phase-3-Trial-of-Next-Generation-COVID-19-Vaccine/default.aspx