The AstraZeneca U.S. Phase III trial of the company’s COVID-19 vaccine (developed in partnership with Oxford University) demonstrated statistically significant vaccine efficacy of 76% at preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and hospitalization.
This interim safety and efficacy analysis was based on 32,449 participants accruing 141 symptomatic cases of COVID-19. The trial had a 2:1 randomization of vaccine to placebo.
Vaccine efficacy was consistent across ethnicity and age. Notably, in participants aged 65 years and over, vaccine efficacy was as high as 85%.
The vaccine was well tolerated, and the independent data safety monitoring board (DSMB) identified no safety concerns related to the vaccine. The vaccine has made headlines recently as some countries decided not to administer it to their citizens (a decision now largely reversed by most of those countries) due to the perceived threat of thrombosis, which was more likely due to a misunderstanding and misreporting of the data. The DSMB conducted a specific review of thrombotic events, as well as cerebral venous sinus thrombosis (CVST) with the assistance of an independent neurologist. The DSMB found no increased risk of thrombosis or events characterized by thrombosis among the 21,583 participants receiving at least one dose of the vaccine. The specific search for CVST found no events in this trial.
Ann Falsey, Professor of Medicine, University of Rochester School of Medicine, U.S., and co-lead Principal Investigator for the trial of the AstraZeneca vaccine, said: “These findings reconfirm previous results observed in trials across all adult populations but it’s exciting to see similar efficacy results in people over 65 for the first time. This analysis validates the AstraZeneca COVID-19 vaccine as a much-needed additional vaccination option, offering confidence that adults of all ages can benefit from protection against the virus.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “These results add to the growing body of evidence that shows this vaccine is well tolerated and highly effective against all severities of COVID-19 and across all age groups. We are confident this vaccine can play an important role in protecting millions of people worldwide against this lethal virus. We are preparing to submit these findings to the U.S. Food and Drug Administration and for the rollout of millions of doses across America should the vaccine be granted U.S. Emergency Use Authorization.”
AstraZeneca will continue to analyze the data and prepare for the primary analysis to be submitted to the U.S. Food and Drug Administration for Emergency Use Authorization in the coming weeks. In parallel, the primary analysis will be submitted for publication in a peer-reviewed journal.
Amongst participants in the interim analysis, approximately 79% were white/Caucasian, 8% black/African American, 4% native American and 4% Asian, and 22% of participants were Hispanic. Approximately 20% of participants were 65 years and over, and approximately 60% had co-morbidities associated with an increased risk for progression of severe COVID-19, such as diabetes, severe obesity or cardiac disease.
This AstraZeneca-led U.S. Phase III trial included two doses administered at a four week interval. Previous trials have shown that an extended interval of up to 12 weeks demonstrated greater efficacy, which was also supported by immunogenicity data. This evidence suggests administration of the second dose with an interval longer than four weeks could further increase efficacy and accelerates the number of people who can receive their first dose.
Following this ‘good news’ announcement from AstraZeneca, the National Institute of Allergy and Infectious Diseases issued a statement on March 23 to say DSMB was “concerned by information released by AstraZeneca on initial data from its COVID-19 vaccine clinical trial” and that the trial may have included outdated information, which “may have provided an incomplete view of the efficacy data”. The statement concluded by urging AstraZeneca to “work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible”.
AstraZeneca responded with its own statement the same day:
“The numbers published yesterday were based on a pre-specified interim analysis with a data cut-off of 17 February. We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis.
“We will immediately engage with the independent data safety monitoring board (DSMB) to share our primary analysis with the most up to date efficacy data. We intend to issue results of the primary analysis within 48 hours.”
Then on March 25, AstraZeneca said after considering the data past the original February 17 cut-off, it had revised its efficacy for symptomatic COVID-19 from 79% to 76% across all age groups and from 80% to 85% for people aged 65 and over. Results showed no change in the 100% efficacy for preventing severe disease.
AstraZeneca said in a statement that the results have been presented to the DSMB, adding that “the primary analysis is pre-specified in the protocol and will be the basis for a regulatory submission for Emergency Use Authorization to the US Food and Drug Administration in the coming weeks”.
While vaccine safety is obviously paramount, care must be taken that concerns over data (where discrepancies are likely to be minor) are addressed prior to statistics being released to the media. And the media must also play its role in presenting facts without sensationalism. Negative headlines are not easily forgotten. In this case, a matter of 3% here and 5% there makes little difference to virus response, but the way in which the release of this data has been handled could be more damaging. Several developers have created and distributed vaccines with high efficacy rates in record time. Let’s not forget that the flu vaccine, which is widely accepted and recommended, has an efficacy of between 40% and 60%. The unprecedented effort by the global medical community to create COVID-19 vaccines with much higher efficacy in record time must not be the victim of public quibbles over data, which in turn could lead to increased vaccine hesitancy.
This story was updated on March 25 to include the latest update from AstraZeneca.