The AstraZeneca Roller Coaster
It has been a wild and unpredictable ride (to date) for the vaccine maker
Once a frontrunner in the race to produce the first COVID-19 vaccine, the road to approval of the Oxford/AstraZeneca has been more like a roller coaster. There have been thrilling announcements about high efficacy and in the same breath, there have been concerns about vaccine safety and transparent presentation of data. As of this evening (information is coming in so fast I have rewritten this post at least three times), AstraZeneca is reporting that its two-dose adenovirus vaccine is safe & effective. It is anticipated that they will submit paperwork to the FDA for an Emergency Use Authorization (EUA) in the coming weeks.
Given the ups and downs, twists and turns of the AstraZeneca vaccine trial (detailed below), it has been suggested by Dr. Nahid Bhadelia, Director of Special Pathogens at the Boston Medical Center that we —
“… wait for the FDA submission packet (from AstraZeneca) just to avoid any further roller coaster rides.”
The AstraZeneca vaccine is an adenovirus vaccine (similar to J&J) that was produced using a modified chimpanzee adenovirus. Like the J&J vaccine, the adenovirus has been altered so that it cannot reproduce in the human body and serves only as a vehicle for the DNA for the spike protein of the SARS-CoV-2 virus. As the demand for COVID vaccine increases worldwide, the AstraZeneca vaccine is key to global vaccination plans, as it is cheap (just a few dollars per dose) and only needs to be refrigerated.
The Phase III clinical trial of the vaccine began in August 2020 with 30,000 individuals enrolling in the study. There was early criticism of the trial because it initially did not include enough participants 55 years of age or older. Within two weeks of initiating the trial, researchers were forced to pause the trial after an adverse reaction was reported by a participant in the UK. It is rumored that this individual developed transverse myelitis. AstraZeneca was criticized for refusing to provide details of the serious adverse reaction. The trial resumed on September 13th in the UK and elsewhere on October 23rd - after the vaccine was determined to be safe.
At the end of November 2020, AstraZeneca released the preliminary results of the trial in anticipation of the UK approving the vaccine (which did happen in December). In the results, AstraZeneca reported that its vaccine was safe and had 70% efficacy against symptomatic COVID-19. No hospitalizations or deaths were reported among those receiving the vaccine.
This encouraging news was quickly overshadowed by the announcement that there was a dosing error in the trial. Approximately, 2/3 of the participants receiving the vaccine (~9000 people) received two full doses 4 weeks apart. The remaining third of the group (~2700) receiving the vaccine received the first shot with only a half dose of vaccine and a full dose with the second shot. Surprisingly, the efficacy of the half dose + full-dose combination was significantly higher (90%) than the two full doses (62%). AstraZeneca reported the efficacy of its vaccine as 70% (a weighted average of the two efficacies). Some called it a manipulation of the data; others accused the company of not being transparent. Dr. David Salisbury sums it up nicely —
“You've taken two studies for which different doses were used and come up with a composite that doesn't represent either of the doses. I think many people are having trouble with that.”
AstraZeneca was also criticized for lacking ethnic, gender, and age diversity in its trial.
However, the vaccine was deemed to be both safe and effective at preventing symptomatic COVID-19 and has been approved for use by the UK, the European Medicines Agency, the Australian Therapeutic Goods Association, and the WHO.
In early March 2021, the distribution of the vaccine was again paused after there were numerous reports of blood clots among individuals who were vaccinated. These blood clots were found mostly in women aged 55 and younger. The European Medicines Agency ruled on March 18th that —
The benefits of the vaccine outweigh the risk of side effects
The vaccine is not associated with an increase in the overall risk of blood clots
There is no evidence of a problem related to specific batches of the vaccine
HOWEVER, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia
On March 22, 2021 - AstraZeneca released better-than-expected efficacy results in its US trial. They reported the two-dose regimen reduced COVID infections by 79% and was 100% effective at preventing hospitalizations and death. These results were quickly overshadowed by a report from the National Institutes of Allergies & Infectious Diseases that the figures presented by AstraZeneca on the 22nd were based on “incomplete information.” Two days later, AstraZeneca released revised data stating that its vaccine was both safe and effective. And it reduced COVID infection by 76%. Among individuals 65+ the vaccine reduced illness 85% of the time.
So now what?
It is anticipated that AstraZeneca will apply for EUA of its COVID vaccine in the United States in the coming weeks. The EUA hearing will center around the question — do the benefits of the AstraZeneca vaccine outweigh the risks? The application materials will be made available to the public (of the FDA’s website), and there will also be an opportunity for public comment on the trial, data, safety, and potential use of the vaccine.
Until then, we all wait. And I recommend that we heed Dr. Bhadelia’s advice to —
“… wait for the FDA submission packet (from AstraZeneca) just to avoid any further roller coaster rides.”