AstraZeneca Likely to Start New Global COVID-19 Vaccine Trial to Verify Effectiveness

AstraZeneca’s COVID-19 vaccine candidate is facing another potential delay as the company plans to undertake a new global clinical trial to confirm the vaccine’s 90 percent efficacy based on a one-and-a-half-dose regimen.

The additional trial of AZD1222 would seek to settle questions about the efficacy results that the company announced last Monday after a fortuitous dosing error revealed that a one-and-a-half-dose was significantly more effective than a double dose.

The company’s CEO Pascal Soriot said he does not expect the new trial to hold up approval of the vaccine in the EU and the UK. But the FDA will most likely ask for more supporting data for the one-and-a-half-dose regimen, said former FDA Commissioner Scott Gottlieb, who believes the new trial may be the deciding factor in whether or not the vaccine gets an Emergency Use Authorization (EUA) from the FDA.

“Most of the data that [AstraZeneca] have on [the one-and-a-half-dose] is … from Brazil and the UK. So, I think FDA is going to want to see more data around that dose, and they’re going to want to see data around that dose on U.S. patients,” Gottlieb said. “My hunch is that AZ is going to need to collect more information.”

Although the vaccine’s one-and-a-half-dose regimen proved to be 90 percent effective, according to AZ’s late-stage interim analysis, questions remain because the half dose was first given to participants by mistake and only 2,741 participants received the smaller dose while almost 9,000 received the double dose (DID, Nov. 25). In addition, the half-dose group were all healthy younger adults who would likely have stronger immune systems than some other participants.

An additional trial could further delay AZ’s efforts to earn an EUA in the U.S., where regulators had already suspended a late-stage trial for a month because of two adverse events believed to be linked to the vaccine. Trials in other countries had restarted weeks earlier after it was determined that the vaccines weren’t to blame for the adverse effects (DID, Oct. 26).

AstraZeneca has not yet filed an application with the FDA for emergency authorization and an additional trial could push a filing further into the future — unless the company bases its application on the 62 percent efficacy rate demonstrated by the double dose or on the average efficacy rate of 70 percent across all participants in the phase 3 trials. The FDA has said it would require “that a COVID-19 vaccine would prevent disease or decrease its severity in at least 50 percent of people who are vaccinated.”

Pfizer is the only company thus far to file for emergency clearance in the U.S., with Moderna expected to file for authorization soon. The FDA’s vaccines advisory committee will meet on Dec. 10 to discuss Pfizer’s candidate, which proved to be 95 percent effective in a final efficacy analysis from its phase 3 trial (DID, Nov. 23). — James Miessler