The Data Safety Monitoring Board (DSMB) for the Phase 3 study of mRNA-1273, Moderna’s vaccine candidate against COVID-19, has confirmed that the trial has met the statistical criteria pre-specified in the study protocol for efficacy, with a vaccine efficacy of 94.5%.
This study, known as the COVE study, enrolled more than 30,000 participants in the U.S. and is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services.
The primary endpoint of the Phase 3 COVE study is based on the analysis of COVID-19 cases confirmed and adjudicated starting two weeks following the second dose of vaccine. This first interim analysis was based on 95 cases, of which 90 cases of COVID-19 were observed in the placebo group versus 5 cases observed in the mRNA-1273 group, resulting in a point estimate of vaccine efficacy of 94.5% (p <0.0001).
A secondary endpoint analyzed severe cases of COVID-19 and included 11 severe cases (as defined in the study protocol) in this first interim analysis. All 11 cases occurred in the placebo group and none in the mRNA-1273 vaccinated group.
The 95 COVID-19 cases included 15 older adults (ages 65+) and 20 participants identifying as being from diverse communities (including 12 Hispanic or LatinX, 4 Black or African Americans, 3 Asian Americans and 1 multiracial).
The interim analysis included a concurrent review of the available Phase 3 COVE study safety data by the DSMB, which did not report any significant safety concerns. A review of solicited adverse events indicated that the vaccine was generally well tolerated. The majority of adverse events were mild or moderate in severity. Grade 3 (severe) events greater than or equal to 2% in frequency after the first dose included injection site pain (2.7%), and after the second dose included fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%) and erythema/redness at the injection site (2.0%). These solicited adverse events were generally short-lived. These data are subject to change based on ongoing analysis of further Phase 3 COVE study data and final analysis.
Preliminary analysis suggests a broadly consistent safety and efficacy profile across all evaluated subgroups.
As more cases accrue leading up to the final analysis, the Company expects the point estimate for vaccine efficacy may change. The Company plans to submit data from the full Phase 3 COVE study to a peer-reviewed publication.
Based on these interim safety and efficacy data, Moderna intends to submit for an Emergency Use Authorization (EUA) with the U.S. Food and Drug Administration (FDA) in the coming weeks and anticipates having the EUA informed by the final safety and efficacy data (with a median duration of at least 2 months). Moderna also plans to submit applications for authorizations to global regulatory agencies.
Stéphane Bancel, Chief Executive Officer of Moderna said: “This is a pivotal moment in the development of our COVID-19 vaccine candidate. Since early January, we have chased this virus with the intent to protect as many people around the world as possible. All along, we have known that each day matters. This positive interim analysis from our Phase 3 study has given us the first clinical validation that our vaccine can prevent COVID-19 disease, including severe disease… We remain committed to and focused on doing our part to help end the COVID-19 pandemic.”
Jeylan Mammadova, Global Sector Lead at Third Bridge commented on the latest vaccine candidate development:
“The speed of Moderna’s and Pfizer’s progress on a potential vaccine is down to starting trials earlier and also an ability to scale production faster than many of their competitors.
“The details around the safety profile and efficacy split across various age groups of the potential vaccines from Pfizer Biotech and Moderna are still unknown and will be as critical to their ultimate success as their speed to market. A good example here is the race between Zostravax and Shingrix, where Zostravax appeared to have higher local reactions with fever and muscle pain but the acceptability of Shingrix was very strong.
“The storage requirements of these potential vaccines are quite different. This could point to Pfizer products being sent to state capitals in more populous cities where there will be high throughput clinics and Moderna’s vaccine being available through community drugstores and pharmacies.
“We are hearing that Pfizer has yet to conduct further stability testing and the -70C storage requirement may not be final. More stability testing could mean more reasonable temperatures, comparable to Moderna and even CureVac.
“It is difficult to conduct direct comparisons between Pfizer Biotech and Moderna as of yet because the assays are not comparable. We do see CD4 and CD8 cells on the Pfizer side however, on Moderna you only see CD4 which may have to do with the sensitivity of the assay. While too early to predict this could also impact the comparative effectiveness of one vaccine over the other.”