AstraZeneca probes 'mistake' behind 90% COVID-19 vaccine efficacy

AstraZeneca is looking into why the accidental use of a half-dose primer vaccine appears to make its COVID-19 regimen more effective. The half-dose was given to some participants due to an error but is now AstraZeneca’s best hope of delivering efficacy comparable to mRNA vaccines.

Most participants in the late-phase analysis received a full dose of AZD1222. The efficacy in that group was 62%, well below the 90%-plus bar set by the Pfizer-BioNTech and Moderna vaccines. A far smaller cohort of subjects received a half-dose primer followed by a full-dose booster. The efficacy in that group was 90%. However, participants were never meant to receive a half-dose primer.

“It was a mistake,” AstraZeneca Executive Vice President Mene Pangalos, Ph.D., told Reuters.

Pangalos said the mistake became apparent when researchers noticed the side effects seen in some participants were milder than expected. An attempt to explain the mild side effects revealed “they had underpredicted the dose of the vaccine by half,” Pangalos said. The participants went on to take a full booster shot. 

The big efficacy question coming out of AstraZeneca’s data drop is whether the 90% figure is a true reflection of the protective power of the half-dose primer regimen. Only 2,741 subjects received the half-dose primer. Pfizer and Moderna enrolled more than 30,000 people in their phase 3 trials.

AstraZeneca was criticized for the data drop, with SVB Leerink analyst Geoffrey Porges saying “the suggestion by the inventors that the small sample given the lower priming dose was evidence of superior efficacy only brings discredit to the program.” 

Ruud Dobber, president of AstraZeneca's U.S. business, told CNBC he expects regulators to focus on the half-dose regimen. The apparent efficacy of the half-dose regimen has led to speculation about why it would be more effective than giving two full doses. Dobber, who admitted the finding was “a little bit of a surprise to all of us,” offered one hypothesis.

“One of the potential hypotheses is that you’re priming the immune system with a relatively low dose or lower dose. As a consequence, the immune system is firing against this virus,” Dobber said.

It will take time to show whether the half-dose regimen really is far more effective and, if so, learn why. Dobber said AstraZeneca plans to do more research in the coming weeks to understand the mechanism.