mRNA-1010 Influenza Vaccine Clinical Trials, Dosage, Indication, Side Effects
Moderna, Inc.'s mRNA-1010 Influenza Vaccine candidate encodes for the hemagglutinin (HA) protein from four seasonal influenza viruses, including seasonal influenza A/H1N1, A/H3N2 and influenza B/Yamagata- and B/Victoria-lineages. mRNA-1010 is Moderna's leading seasonal influenza mRNA vaccine candidate to enter the phase 3 study in a clinic, says the Company. Moderna's mRNA medicines and platform use normal biological processes to express proteins and create a desired therapeutic effect. This enables the potential treatment of a broad spectrum of diseases, many of which cannot be addressed with current technologies.
Positive interim data from the Phase 1 study of mRNA-1010 was announced on December 10, 2021. In the study, mRNA-1010 successfully boosted hemagglutination inhibition assay geometric mean titers against all strains 29 days after vaccination at doses tested in younger and older adults. The Phase 2 study of mRNA-1010 was initiated in November 2021 to confirm dose across three levels, including a lower 25 µg dose level and the two lowest dose levels from Phase 1 (50 µg and 100 µg) with approximately 150 participants per arm. In addition, the Phase 2 study includes an approved flu vaccine comparator arm (N=50).
As of February 16, 2023, Moderna announced interim results from its pivotal Phase 3 safety and immunogenicity trial of mRNA-1010 (P301); this Phase 3 randomized, observer-blind study enrolled 6,102 adults across Argentina, Australia, Colombia, Panama, and the Philippines during the Southern Hemisphere influenza season. In this study, mRNA-1010 was found to be generally well-tolerated. However, 70% of mRNA-1010 recipients reported SARs compared to 48% of participants in the active comparator group. A lower rate of solicited adverse reactions (SARs) was observed in older age groups than in younger adult groups. The majority of SARs were grade 1. Pain and axillary swelling were the most common local SARs, and headache, myalgia, and fatigue were the most common systemic SARs reported. No significant differences in unsolicited adverse events, serious adverse events, or adverse events of special interest were observed between the mRNA-1010 and comparator groups.
On June 19, 2023, the journal Nature Communications published an article concluding that interim data support the continued development of mRNA-1010. No safety concerns were identified; solicited adverse reactions were dose-dependent and more frequent after receipt of mRNA-1010 than the active comparator.
Moderna announced on September 13, 2023, that mRNA-1010 demonstrated an acceptable safety and tolerability profile across all clinical trials to date, including three Phase 3 trials (P301, P302, P303), and independent data and safety monitoring boards (DSMBs) have raised no safety concerns. On March 27, 2024, Moderna announced that in the most recent Phase 3 trial (P303), which was designed to test the immunogenicity and safety of an optimized vaccine composition, mRNA-1010 met all immunogenicity primary endpoints, demonstrating higher antibody titers compared to a currently licensed standard-dose flu vaccine. In the P303 study, mRNA-1010 met all immunogenicity primary endpoints, demonstrating higher antibody titers than a licensed standard-dose flu vaccine (Fluarix®). In an older adult extension study of P303, mRNA-1010 met all primary immunogenicity, including superiority for all compared to a licensed enhanced flu vaccine (Fluzone HD®), and showed an acceptable reactogenicity profile.
Blackstone announced a collaboration agreement with Moderna on March 24, 2024, providing up to $750 million to fund Moderna's influenza vaccine program.
Cambridge, MA-based Moderna Inc.'s mRNA vaccine technology offers potential advantages in efficacy, speed of development, and production scalability and reliability, which may position the Company as a leader in preparing for and responding to infectious disease threats that place millions of people at risk worldwide. To learn more, visit www.modernatx.com.
mRNA-1010 Indication
mRNA-1010 Influenza Vaccine is indicated to prevent seasonal influenza of the four influenza strains the World Health Organization recommended.
mRNA-1010 Dosage
In the Phase 1 study, mRNA-1010 was evaluated at 50 µg, 100 µg, and 200 µg dose levels in younger adult (age 18-49) and older adult (age 50+) cohorts. A minimal dose response was observed between the 50 µg, 100 µg, and 200 µg doses. No significant safety findings were observed through day 29.
At the lowest dose level (50 µg) in younger adults, Day 29 geometric mean titers (GMT) against influenza A strains were 538 (H1N1) and 530 (H3N2); GMT against influenza B strains were 467 (B/Yamagata) and 261 (B/Victoria). Geometric mean fold-rises (GMFR) above baseline for influenza A strains were approximately 10-fold (H1N1) and 8-fold (H3N2), and about 3-fold for B/Yamagata and 2-fold for B/Victoria. In addition, a minimal dose response was observed between the 50 µg, 100 µg, and 200 µg dose levels, suggesting the potential to explore even lower doses.
At the lowest dose level (50 µg) in older adults, Day 29 GMT against influenza A strains were 310 (H1N1) and 263 (H3N2); GMT against influenza B strains were 305 (B/Yamagata) and 215 (B/Victoria). GMFR for influenza A strains was approximately 6-fold (H1N1) and 6-fold (H3N2), approximately 3-fold for B/Yamagata, and 2-fold for B/Victoria.
mRNA-1010 Side Effects
Adverse reactions were reported more frequently in younger adults compared to older adults and at higher dose levels in the phase 1 study. The most common solicited local responses for both age groups included pain and axillary swelling/tenderness. The most common solicited systemic ARs for both age groups included fatigue, arthralgia, myalgia, and headache.
mRNA-1010 Vaccine News
September 12, 2024 - Moderna announced that it is no longer pursuing an accelerated approval pathway for the regulatory submission of its standalone flu vaccine, mRNA-1010, to focus its resources on the submission of a potentially more impactful flu/COVID combination vaccine, mRNA-1083, this year. The Company plans to start a confirmatory vaccine efficacy study for mRNA-1010 in 2024, funded by previously announced project financing through Blackstone Life Sciences.
March 27, 2024 - "Moderna is advancing a broad and diverse pipeline at a pace not seen before in our industry," said Stéphane Bancel, Moderna's Chief Executive Officer, in a press release.
September 13, 2023 - Moderna Inc. continues to advance a portfolio of influenza vaccine candidates that include additional HA antigens for broader coverage of circulating influenza A strains (mRNA-1011 and mRNA-1012) and candidates that incorporate both HA and neuraminidase (NA) antigens to target multiple proteins involved in the influenza virus lifecycle to reduce the potential of viral antigenic escape (mRNA-1020 and mRNA-1030).
May 4, 2023 - Moderna confirmed an additional Phase 3 trial (P302) is being conducted in the Northern Hemisphere to evaluate the safety and non-inferior efficacy compared to a licensed flu vaccine. The independent DSMB has completed the first interim efficacy analysis and informed the Company that mRNA-1010 did not meet the statistical threshold necessary to declare early success. It is recommended that the trial continues with efficacy follow-up towards the following analysis.
April 11, 2023 - Moderna announced it had developed an update to mRNA-1010 that is expected to have improved immunogenicity against influenza B strains and plans to initiate a confirmatory Phase 3 trial in April 2023.
February 16, 2023 - Stephen Hoge, M.D., Moderna's President, stated in a press release," While we did not achieve non-inferiority for the Influenza B strains, which are more frequent in younger populations, we have already updated the vaccine that we believe could improve immune responses against Influenza B and will seek to quickly confirm those improvements in an upcoming clinical study thanks to the agility of our mRNA platform."
August 3, 2022 - Moderna Inc. reported the Phase 3 safety and immunogenicity trial started in June 2022 in the Southern Hemisphere for seasonal flu vaccine candidate (mRNA-1010) to support potential accelerated approval.
March 14, 2022—An analysis—Moderna and Novavax's combination vaccine candidate draws expert enthusiasm for efficacy owing to the former's mRNA vaccine technology and the latter's noninferior data for its standalone protein subunit flu vaccine, which is conducting a phase 1/2 clinical study.
December 10, 2021 - Moderna, Inc. announced the first positive interim data from the Phase 1 study of the Company's quadrivalent seasonal flu vaccine candidate, mRNA-1010. In the study, mRNA-1010 successfully boosted hemagglutination inhibition assay geometric mean titers against all strains 29 days after vaccination at doses tested in younger and older adults. The Company also announced that the Phase 2 study of mRNA-1010 is now fully enrolled, and the preparation for the Phase 3 study is underway. In addition, Moderna also updated its seasonal flu vaccine program, announcing two beyond quadrivalent seasonal flu development candidates (mRNA-1011 and mRNA-1012).
July 7, 2021 - Moderna Announces First Participant Dosed in Phase 1/2 Study of Its Quadrivalent Seasonal Flu mRNA Vaccine. This Phase 1/2 randomized, stratified, observer-blind, dose-ranging study will evaluate the safety, reactogenicity, and immunogenicity of mRNA-1010, Moderna's seasonal influenza vaccine candidate, in healthy adults 18 years and older in the U.S. The Company intends to enroll approximately 180 participants in the study. mRNA-1010 is Moderna's first seasonal influenza vaccine candidate to enter the clinic. It targets lineages the WHO recommended to prevent influenza, including seasonal influenza A H1N1, H3N2, and influenza B Yamagata and Victoria.
January 11, 2021 - Moderna, Inc. revealed influenza vaccine candidates (mRNA-1010, mRNA-1020, mRNA-1030) in a press release. This first-generation flu program will evaluate multiple candidates comprising multiple antigen combinations against the four seasonal viruses recommended by the WHO. Phase 1 clinical trials for the program are expected to begin in 2021.
mRNA-1010 Clinical Trials
The Phase 3 randomized, observer-blind study is designed to evaluate the safety and immunological non-inferiority of mRNA-1010 to a licensed seasonal influenza vaccine in adults 18 years and older. Participants will be randomly assigned on a 1:1 ratio to receive either a single dose of mRNA-1010 or a licensed seasonal influenza vaccine dose as a comparator. In an interim analysis of the P303 study,mRNA-1010 met all co-primary endpoints across all four A and B strains (A/H1N1, A/H3N2, influenza B/Yamagata, B/Victoria). Higher HAI geometric mean titers and seroconversion rates were observed for all four strains compared to a licensed comparator (Fluarix). Local and systemic solicited adverse reactions were similar to those reported in previous mRNA-1010 studies.
Improved immunogenicity was observed across age groups and, importantly, in older adults. mRNA-1010 also elicited higher HAI titers against A/H1N1, A/H3N2, B/Victoria, and comparable titers to B/Yamagata compared to Fluzone HD in a separate Phase 1/2 head-to-head study. Based on these data, consultations with regulators on a potential licensing package are ongoing.
This Phase 1/2 randomized, stratified, observer-blind, dose-ranging study will evaluate the safety, reactogenicity, and immunogenicity of mRNA-1010, Moderna's seasonal influenza vaccine candidate, in healthy adults 18 years and older in the U.S. The Company intends to enroll approximately 180 participants in the study. The Phase 2 study of mRNA-1010 was initiated in November to confirm dose across three doses, including a lower 25 µg dose level and the two lowest dose levels from Phase 1 (50 µg and 100 µg) with approximately 150 participants per arm. In addition, the Phase 2 study includes an approved flu vaccine comparator arm (N=50). The Phase 2 study was fully enrolled in November (N=500), and an interim analysis is expected in early 2022. Preparation for the Phase 3 study for mRNA-1010, including manufacturing, is already underway. The Company seeks guidance from global regulatory agencies on the Phase 3 program.
