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)
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 µg and 100 µg dose levels, mRNA-1273 was generally well-tolerated in all age cohorts
“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
Both the 25 µg and 100 µg 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 µg dose and fatigue in one participant in the ages 71+ cohort who received the 100 µg 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 µg and 100 µg 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 μg 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 μg 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 µg dose in the 56-70 age cohort and the 100 µg 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.
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
The Phase 3 COVE study of mRNA-1273, being conducted in collaboration with the
About Moderna’s Prophylactic Vaccines Modality
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.
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)
Vaccines against infections transmitted from mother to baby
- Cytomegalovirus (CMV) vaccine (mRNA-1647)
- Zika vaccine (mRNA-1893 with BARDA)
Vaccines against highly prevalent viral infections
- Epstein-Barr virus (EBV) vaccine (mRNA-1189)
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended including, but not limited to, statements concerning the potential for mRNA-1273 to generate binding and neutralizing antibodies in older adults, the potential for adverse side effects from mRNA-1273, the U.S. government’s potential purchases of mRNA-1273, the acceleration of the Company’s development of its vaccine pipeline, and the potential benefits of mRNA-based prophylactic vaccine development. In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others: preclinical and clinical development is lengthy and uncertain, especially for a new class of medicines such as mRNA, and therefore our preclinical programs or development candidates may be delayed, terminated, or may never advance to or in the clinic; no commercial product using mRNA technology has been approved, and may never be approved; mRNA drug development has substantial clinical development and regulatory risks due to the novel and unprecedented nature of this new class of medicines; despite having ongoing interactions with the FDA or other regulatory agencies, the FDA or such other regulatory agencies may not agree with the Company’s regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted; the fact that the rapid response technology in use by
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