Moderna Announces Publication in The New England Journal of Medicine of Interim Results From Older Adult Age Cohorts in Phase 1 Study of its mRNA Vaccine Against COVID-19 (mRNA-1273)
September 29, 2020 at 6:17 PM EDT
mRNA-1273 induced consistently high levels of pseudovirus neutralization antibody titers in all participants in the 56-70 (n=10) and 71+ (n=10) age cohorts
Potent neutralization responses were confirmed by 3 different live virus assays
mRNA-1273 elicited Th1-biased CD4 T cell responses in the 56-70 and 71+ age cohorts
Neutralizing antibody titers and T cell responses in the 56-70 and 71+ age cohorts were consistent with those reported in younger adults
At the 25 ?g and 100 ?g dose levels, mRNA-1273 was generally well-tolerated in all age cohorts
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Sep. 29, 2020--?Moderna, Inc., (Nasdaq: MRNA) a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, today announced the publication of the second interim analysis of the open-label Phase 1 study of mRNA-1273, its vaccine candidate against COVID-19, in?The New England Journal of Medicine. This interim analysis evaluated a two-dose vaccination schedule of mRNA-1273 given 28 days apart in 40 healthy adult participants across two dose levels (25 and 100 ?g) in two age cohorts (ages 56-70 and ages 71+), and reports results through Day 57 (1 month after the second dose). This analysis found that both the 25 ?g and 100 ?g dose levels were generally well-tolerated in both age cohorts. Immune responses were dose-dependent with the 100 ?g dose eliciting higher binding and neutralizing antibody titers, supporting the selection of the 100 ?g dose for further study in the Phase 3 trial. The study was led by the?National Institute of Allergy and Infectious Diseases?(NIAID), part of the?National Institutes of Health?(NIH). ?These interim Phase 1 data suggests that mRNA-1273, our vaccine candidate for the prevention of COVID-19, can generate neutralizing antibodies in older and elderly adults at levels comparable to those in younger adults,? said?Tal Zaks, M.D., Ph.D., Chief Medical Officer of?Moderna. ?Given the increased morbidity and mortality of COVID-19 in older and elderly adults, these data give us optimism in demonstrating mRNA-1273?s protection in this population, which is being evaluated in the Phase 3 COVE study.? Both the 25 ?g and 100 ?g dose levels of mRNA-1273 were generally well-tolerated, with no serious adverse events reported through Day 57. The most common solicited adverse events were headache, fatigue, myalgia, chills, and pain at the injection site, the majority of which were mild-to-moderate in severity and of self-limited duration. Local and systemic reactogenicity were more common and more frequently moderate in severity after the second dose. Two severe solicited systemic adverse events occurred following the second vaccination: fever in one participant in the ages 56-70 cohort who received the 25 ?g dose and fatigue in one participant in the ages 71+ cohort who received the 100 ?g dose. Clinical laboratory values of Grade 2 or higher revealed no pattern of concern. Participants will continue to be followed through 13-months to allow for a longer assessment of vaccine-related adverse events. At both the 25 ?g and 100 ?g dose levels, after two vaccinations, mRNA-1273 induced dose-dependent binding antibody responses reaching the upper quartile of the distribution of convalescent sera. At Day 57 (1 month post-dose 2), geometric mean titers (GMT) exceeded the median of those seen in convalescent sera from 41 individuals with confirmed COVID-19 diagnosis. Neutralizing activity was assessed with multiple assays, including a pseudovirus neutralization assay (pseudotyped lentivirus reporter single-round-of-infection neutralization assay [PsVNA]) against the two most common SARS-CoV-2 variants (614D and 614G) and three live-virus neutralization assays (SARS-CoV-2 nanoluciferase high-throughput neutralization assay [nLUC HTNA], focus reduction neutralization test mNeonGreen [FRNT-mNG] and classical plaque-reduction neutralization test [PRNT]). No participants had detectable neutralizing responses by any assay prior to vaccination, and robust neutralizing activity was observed in all participants 14 days after the second vaccination. Pseudovirus neutralization responses were observed as early as seven days after the second vaccination and were dose-dependent across all age groups (18-55, 56-70 and 71+). At Day 43 at the 100 ?g dose level, PsVNA ID50?titers in the older adult cohorts ages 56-70 (GMT 402) and 71+ (GMT 317) were comparable to those seen in the age 18-55 cohort (GMT 360), and 3- to 4-fold higher than those seen in convalescent sera (GMT 106). Titers remained high through four weeks after the second dose in all age cohorts. Neutralizing activity against the 614G variant was also observed at the 100 ?g dose in all age cohorts. Results were consistent using 3 live virus assays. Neutralizing antibody titers as measured by nLUC HTNA and FRNT-mNG were similar across all age groups (18-55, 56-70 and 71+). At Day 43, PRNT80?GMT in the 100 ug dose groups was 878 in the 56-70 and 317 in the 71+ age cohort, representing 5.5 and 2.0-fold above convalescent sera respectively, and 4.1-fold above convalescent sera in the 18-55 age group (GMT 654). The 25 ?g dose in the 56-70 age cohort and the 100 ?g dose level across all age groups (18-55, 56-70 and 71+) elicited a strong Th1-biased CD4 T cell response. The U.S. government has agreed to purchase 100 million doses of mRNA-1273, with an option to purchase an additional 400 million doses. About mRNA-1273 mRNA-1273 is an mRNA vaccine against COVID-19 encoding for a?prefusion stabilized?form of the Spike (S) protein, which was co-developed by?Moderna?and investigators from the National Institute of Allergy and Infectious Disease?s (NIAID)?Vaccine Research Center. The first clinical batch, which was funded by the?Coalition for Epidemic Preparedness Innovations, was completed on?February 7, 2020?and underwent analytical testing; it was shipped to the?National Institutes of Health (NIH) on?February 24, 42 days from sequence selection. The first participant in the NIAID-led Phase 1 study of mRNA-1273 was dosed on?March 16, 63 days from sequence selection to Phase 1 study dosing. On?May 12, the FDA granted mRNA-1273 Fast Track designation. On?May 29, the first participants in each age cohort: healthy adults ages 18-55 years (n=300) and older adults ages 55 years and above (n=300) were dosed in the Phase 2 study of mRNA-1273. On?July 8, the?Phase 2 study?completed enrollment. The?Phase 3 COVE study?of mRNA-1273, being conducted in collaboration with the?NIH?and BARDA, began on?July 27. Results from a non-human primate preclinical viral challenge study evaluating mRNA-1273 were recently?published?in?The New England Journal of Medicine.?On?July 14, an interim analysis of the original cohorts in the?NIH-led Phase 1 study of mRNA-1273 was?published?in?The New England Journal of Medicine. A summary of the company?s work to date on COVID-19 can be found?here. The Biomedical Advanced Research and Development Authority?(BARDA), part of the?Office of the Assistant?Secretary for Preparedness and Response (ASPR) within the?U.S. Department of Health and Human Services?(HHS), is supporting the continued research and development of mRNA-1273 with?$955 million?in federal funding under Contract no. 75A50120C00034. BARDA is reimbursing?Moderna?for 100 percent of the allowable costs incurred by the company for conducting the program described in the BARDA contract. The U.S. government has committed up to $1.525 billion to purchase supply of mRNA-1273 under U.S. Department of Defense Contract No. W911QY-20-C-0100. About Moderna?s Prophylactic Vaccines Modality Moderna?scientists designed the company?s prophylactic vaccines modality to prevent infectious diseases. More than 1,900 participants, prior to enrolling the Phase 3 study of mRNA-1273, have been enrolled in Moderna?s infectious disease vaccine clinical studies under health authorities in the?U.S.,?Europe?and?Australia. Clinical data demonstrate that Moderna?s proprietary vaccine technology has been generally well-tolerated and can elicit durable immune responses to viral antigens. Based on clinical experience across Phase 1 studies, the company designated prophylactic vaccines a core modality and is working to accelerate the development of its vaccine pipeline. The potential advantages of an mRNA approach to prophylactic vaccines include the ability to combine multiple mRNAs into a single vaccine, rapid discovery to respond to emerging pandemic threats and manufacturing agility derived from the platform nature of mRNA vaccine design and production.?Moderna?has built a fully integrated manufacturing plant which enables the promise of the technology platform. Moderna?currently has?nine development candidates?in its prophylactic vaccines modality, including: Vaccines against respiratory infections- Respiratory syncytial virus (RSV) vaccine for older adults (mRNA-1777 and mRNA-1172 or V172 with Merck)
- RSV vaccine for young children (mRNA-1345)
- Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) vaccine (mRNA-1653)
- COVID-19 vaccine (mRNA-1273)
- Influenza H7N9 vaccine (mRNA-1851)
- Cytomegalovirus (CMV) vaccine (mRNA-1647)
- Zika vaccine (mRNA-1893 with BARDA)
- Epstein-Barr virus (EBV) vaccine (mRNA-1189)
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Media: Colleen Hussey Senior Manager, Corporate Communications 617-335-1374 Colleen.Hussey@modernatx.com Investors: Lavina Talukdar Head of Investor Relations 617-209-5834 Lavina.Talukdar@modernatx.com Source:?Moderna, Inc.