mRNA-1010 Quadrivalent Influenza Vaccine 2023

Moderna, Inc.'s mRNA-1010 Quadrivalent 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 first of five seasonal influenza mRNA vaccine candidates to enter the clinic, says the Company. 

mRNA medicines take advantage of 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 the Company's quadrivalent seasonal flu vaccine candidate, 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). The Phase 2 study was fully enrolled in November (N=500), and an interim analysis is expected in early 2022.

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 was designed to evaluate the safety and immunological non-inferiority of mRNA-1010 to a licensed seasonal influenza vaccine in adults 18 years and older. The trial enrolled 6,102 adults across Argentina, Australia, Colombia, Panama, and the Philippines during the Southern Hemisphere influenza season. Participants were randomly assigned to receive either a single dose of mRNA-1010 or a single dose of a licensed seasonal influenza vaccine as a comparator. mRNA-1010 encodes for hemagglutinin (HA), a major influenza surface glycoprotein considered an important target to generate protection against influenza and is the primary target of currently available influenza vaccines.

In this study, mRNA-1010 was found to be generally well-tolerated. 70% of mRNA-1010 recipients reported solicited adverse reactions (SARs) compared to 48% of participants in the active comparator group. A lower rate of SARs was observed in older age groups compared to the 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.

And the ongoing mRNA-1010 Phase 3 efficacy study (P302) conducted in Northern Hemisphere countries has accrued more than 200 PCR-confirmed cases. Consistent with the predominant circulation of A/H3N2 and A/H1N1 viruses during this influenza season, more than 99% of confirmed cases in the study are caused by influenza A viruses. The first per-protocol interim analysis of efficacy is now expected to be reviewed by an independent Data and Safety Monitoring Board (DSMB) before the end of the first quarter. Based on these results, the DSMB will notify the Company whether the primary efficacy endpoint has been met or whether the study should continue accruing further cases toward the final analysis.

Cambridge, MA-based Moderna'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 around the world. To learn more, visit www.modernatx.com.

mRNA-1010 Indication

mRNA-1010 Quadrivalent Influenza Vaccine is indicated to prevent seasonal influenza of the four influenza strains recommended by the World Health Organization.

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. 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 were 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 News

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."

January 9, 2023 - Moderna Inc. confirmed phase 3 studies were progressing.

September 8, 2022 - Moderna announced it is preparing to launch a Phase 3 efficacy trial in the Northern Hemisphere to demonstrate the superior effectiveness of mRNA-1010 against currently licensed flu shots.

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. The Company is preparing for a Phase 3 efficacy study in the fall of 2022 (if needed).

June 7, 2022 - Moderna, Inc. announced the first participants had been dosed in a Phase 3 study of the Company's seasonal influenza vaccine candidate mRNA-1010.

May 4, 2022 - The Company announced first quarter 2022 revenues of $6.1 billion and GAAP net income of $3.7 billion.

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).

November 4, 2021 - Moderna provided updates on several of its products. "We look forward to sharing data from the Phase 1 study of our flu vaccine candidate soon, and we are preparing to start our Phase 2 study. Phase 1 portion of the Phase 1/2 study of quadrivalent seasonal flu vaccine candidate (mRNA-1010) fully enrolled, preparations for Phase 2 portion of the study are ongoing."

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 World Health Organization (WHO) recommended to prevent influenza, including seasonal influenza A H1N1, H3N2, and influenza B Yamagata and Victoria.

January 11, 2021 - Moderna, Inc. revealed in a press release influenza vaccine candidates (mRNA-1010, mRNA-1020, mRNA-1030). 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 single dose of a licensed seasonal influenza vaccine as a comparator.

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 dose 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). 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 is already underway, including manufacturing. The Company seeks guidance from global regulatory agencies on the Phase 3 program.