Rejecting sharp criticism from U.S. government scientists, AstraZeneca said Wednesday night that its Covid-19 vaccine was 76% effective at reducing the risk of symptomatic Covid-19, and 100% effective against severe disease, in a new analysis of its large U.S.-based clinical trial.
Those estimates were just a few percentage points lower than much more sparse results the company released Monday from an earlier analysis of the study, despite dramatic statements from government scientists that AstraZeneca’s initial release may have used “outdated information” that could have been overly favorable.
AstraZeneca said Monday that the vaccine was 79% effective at preventing symptomatic Covid-19 based on 141 cases of Covid-19 that occurred in the 32,000-patient study, which was conducted with the National Institutes of Health. That would appear very similar to the results in the updated analysis, which is based on 190 cases from the trial. There are still 14 possible or probable Covid-19 cases that researchers want to double-check before including, but those would be unlikely to substantially change the final results.
The new company data come after considerable drama, when the government agency that helped run the trial challenged AstraZeneca’s credibility. Early Tuesday, the National Institute of Allergy and Infectious Diseases, a part of the NIH, issued a statement saying that the earlier figures may have been based on “incomplete information.”
The data and safety monitoring board for the trial, a key committee charged with overseeing patient safety and trial integrity, had written a harsh letter to AstraZeneca and copied the leadership of NIAID and the Biomedical Advanced Research and Development Authority, another part of the U.S. government. NIAID decided to make the clash public, and its head, Anthony Fauci, characterized AstraZeneca’s Monday release as “an unforced error.”
STAT reached out to Fauci Wednesday night but he did not immediately reply.
Eric Topol, director of the Scripps Research Translational Institute, said that the results were “better than expected” given the clash between the DSMB and AstraZeneca. He added that he is “relieved since the world needs the vaccine badly.”
AstraZeneca did not detail its conversations with the DSMB about its latest analysis, saying only, “These results have been presented to the independent Data Safety Monitoring Board.” A company spokesperson would not explain what that sentence meant, but said that the press release was shared with the DSMB, and the primary analysis is prespecified.
The primary endpoint, vaccine efficacy at preventing symptomatic Covid-19, was 76% for infections occurring 15 days or more after receiving two doses given four weeks apart. Results were similar in different age groups, with vaccine efficacy of 85% in adults 65 years and older.
In preventing severe or critical disease and hospitalization, the vaccine demonstrated 100% efficacy. There were eight cases of severe Covid-19 observed in that analysis, with all of those cases in the placebo group.
That number of cases is more than it sounds, because two-thirds of the patients received vaccine and only one-third placebo, but eight is still a small number of cases upon which to draw a firm conclusion about how protective the vaccine is against severe disease. Moderna, the developer of another Covid-19 vaccine, had 30 cases of severe disease in its study.
Based on a statistical measure called confidence intervals given in the press release, the end result on overall efficacy could be anywhere between 68% and 82% — figures that would more than pass the Food and Drug Administration’s criteria for an emergency use authorization. AstraZeneca said it would file for such an authorization in the coming weeks.
All the results look more robust than data from an earlier pooled analysis of clinical trials in the U.K., South Africa, and Brazil, which showed a roughly 62% efficacy for the vaccine.
After all the twists and turns, though, several researchers reached by STAT said they would prefer to wait until more results are available before drawing firm conclusions. AstraZeneca has said it would publish the results in a peer-reviewed medical journal. In deciding whether to grant an authorization, the FDA will rely not on AstraZeneca’s estimates but on its own analysis of the raw data.
Or, as Nahid Bhadelia, the director of the special pathogens unit at Boston Medical Center, put it on Twitter: “At this point, I will wait for the FDA submission packet just to avoid any further roller coaster rides.”