AstraZeneca Faces Questions About Mistake That Led to 90 Percent Effective Regimen

AstraZeneca’s COVID-19 vaccine candidate will undergo increased scrutiny by regulators because of the promising but confusing interim analysis results from a late-stage trial that found a one-and-a- half-dose regimen — given by mistake — was significantly more effective than a full double dose.

Participants in the trials were at first given the one-and-a-half-dose regimen by mistake, the company said. The one-and-a-half-dose regimen wound up showing 90 percent efficacy compared to 62 percent efficacy for the double-dose regimen, though AstraZeneca (AZ) acknowledges it’s not yet clear why.

The one-and-a-half-dosing regimen group consisted of 2,741 participants, a significantly smaller amount than the double-dose group, which was made up of 8,895 participants. The error and size differences between the groups could potentially threaten the regulatory pathway for the promising vaccine, AZD1222, and the fact that the efficacy rates were based on an accident raises questions about the validity of the data.

Researchers reportedly discovered the mistake after they saw weaker vaccine side effects in participants than anticipated. Apparently, the error occurred because of a mismeasurement in the vaccine vials. After finding the one-and-a-half dose regimen given in error actually produced much higher efficacy results than the full two-dose regimen, they decided to continue using the one-and-a-half-dose regimen moving forward.

The FDA, which has not yet commented on the situation, could ask the company to collect more data due to the mistake, which could delay receiving Emergency Use Authorization (EUA).

“What we are now looking to analyze is what immune response has been induced in those who have received the half dose and the full dose vs. those that have received twice the full dose and understand whether there are differences in the immune response induced,” Moncef Slaoui, chief adviser for Operation Warp Speed, said during an HHS briefing Tuesday. “There are a number of variables that we need to understand and what has been the role of each one of them in achieving the difference in efficacy.”

Once those variables are understood, Slaoui said, a decision can be made on the U.S. late-stage trial of the AZ vaccine, including how to interpret the validity of the one-and-a-half-dose regimen that showed such high efficacy. “We want it to be based on data and science because we understand the input, but we don’t understand the consequences of the input,” he said.

AZ did not immediately respond to requests for comment. — James Miessler