Interim Data Suggests AstraZeneca Covid-19 Vaccine Effective, Safe

Interim results showed the Oxford-AstraZeneca Covid-19 vaccine to have acceptable efficacy with a good safety profile, but questions remain about the vaccine, including its effectiveness in elderly people.

Early efficacy results involving data from 2 of 4 ongoing trials of the ChAdOx1 nCoV-19 vaccine, or AZD1222, were published Tuesday in The Lancet

The results are the first phase III efficacy findings for a Covid-19 vaccine to be published in a peer-reviewed journal.

The U.S. government had pledged to buy 300 million doses of the vaccine from the company if trials showed it to be effective and safe. While AstraZeneca vowed to have the vaccine available in the U.S. by the fall, as of December the company was still enrolling people in the U.S. clinical trial, according to a report in the New York Times, which attributed the delay to the company’s failure to provide key safety data to the FDA related to the halting of the studies.

The ChAdOx1 nCoV-19 vaccine, which was developed at Oxford University, uses a chimpanzee adenovirus viral vector that cannot cause disease in humans and expresses the SARS-CoV-2 spike protein.

Safety studies conducted prior to the first outbreak of Covid-19 showed the vaccine to be protective against another coronavirus — Middle East respiratory syndrome (MERS).

While the overall efficacy of 70% reported in the interim analysis was lower than that reported for mRNA vaccines being developed by the pharmaceutical companies Pfizer and Moderna, the Oxford-AstraZeneca vaccine has significant potential advantages. The vaccine is both cheaper and easier to store than these and several other potential rival vaccines, as previously reported by BreakingMED.

The low dose/standard dose regimen reported in the interim analysis occurred because of a mistake in one of the trials conducted in the United Kingdom, where participants inadvertently received half doses (low doses) of the vaccine as a first dose.

AstraZeneca’s failure to initially acknowledge the dosing error was also widely criticized, and on Tuesday several commentators said their concerns about the interpretation of the findings were not put to rest by the publication of the trial data in the peer-reviewed journal.

“It’s a mess,” Weill Cornell Medical College virologist John Moore, PhD, told BuzzFeed News. “The vaccine clearly works, but we still don’t know how well.”

In an editorial published with the study, Maria Deloria Knoll, PhD, and Chizoba Wonodi, MBBS, of Johns Hopkins Bloomberg School of Public Health, Baltimore, wrote that the lower cost (U.S. $2-3 per dose) and easier storage of the ChAdOx1 nCoV-19 vaccine “holds good promise for equitable access for low income and middle income countries, compared with the high cost of the two mRNA vaccines that have reported more than 90% efficacy.”

“Trust and confidence in any Covid-19 vaccine will be crucial to its success,” Knoll and Wonodi added. “The appropriate pausing of the trial to carefully investigate for safety concerns generated much publicity despite the reassuring outcomes of the safety review and trial recommencement… Public concerns might have been raised by the unplanned administration of different doses, notwithstanding that the per-protocol primary results exceeded licensure thresholds and that the serendipitous findings for recipients of the mixed-dose regimen were of higher efficacy.”

Knoll and Wonodi noted that despite remaining questions about the Oxford-AstraZeneca and other vaccines, “it is hard not to be excited about these findings and the existence of three safe and efficacious Covid-19 vaccines, with a further 55 already in clinical trials.”

The interim analysis included data on 11,636 adult participants recruited for trials in the United Kingdom and Brazil.

Among the main findings:

• In participants receiving two standard doses (5×10¹⁰ viral particles) of the vaccine, efficacy was 62.1% (95% CI 41.0–75.7; 27 [0.6%] of 4,440 in the ChAdOx1 nCoV-19 group versus 71 [1.6%] of 4,455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90.0% (67.4–97.0; three [0.2%] of 1,367 versus 30 [2.2%] of 1,374; P_interaction=0.010).
• From 21 days after the first dose, there were ten cases hospitalized for Covid-19, all in the control arm of the studies. Two were classified as severe Covid-19, including one death.
• There were 74,341 person-months of safety follow-up (median 3.4 months, IQR 1.3–4.8). A total of 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group.
• Three adverse events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remained masked to group allocation at data publication.

“Until widespread immunity halts the spread of SARS-CoV-2, physical distancing measures and novel therapies are needed to control Covid-19,” the researchers concluded. “In the meantime, an efficacious vaccine has the potential to have a major impact on the pandemic if used in populations at risk of severe disease. Here, we have shown for the first time that a viral vector vaccine, ChAdOx1 nCoV-19, is efficacious and could contribute to control of the disease in this pandemic.”

1. Interim results showed the Oxford-AstraZeneca Covid-19 vaccine to have acceptable efficacy with a good safety profile, but questions remain about the vaccine, including its effectiveness in elderly people.

2. The vaccine was found to have an overall efficacy of around 70%, with an efficacy of 62% in participants receiving 2 standard doses of vaccine and a 90% efficacy in those receiving a half dose as their first injection and a standard dose as their second injection.

Salynn Boyles, Contributing Writer, BreakingMED™

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