US trial of AstraZeneca COVID-19 vaccine shows 74% efficacy, 83.5% in those above 65

AstraZeneca or the Oxford vaccine was safe and had 74% efficacy at preventing symptomatic SARS-CoV-2, and it increased to 83.5% in people aged 65 across diverse populations that included older adults in the United States, Chile, and Peru, stated the results of the company’s clinical trial published in The New England Journal of Medicine on September 29.

The paper stated that high vaccine efficacy was consistent across a range of demographic subgroups. The trial revealed that the estimated vaccine efficacy for preventing SARS-CoV-2 infection was 64.3%. The antibodies as a result of the vaccine increased after the first dose and increased further when they were measured 28 days after the second dose.

These were the results from the primary analysis of a pivotal phase 3, double-blind, placebo-controlled trial that assessed the safety, efficacy, and immunogenicity of two doses of AstraZeneca vaccine (AZD1222) administered four weeks apart for the prevention of symptomatic Covid-19. This is an ongoing trial conducted at 88 sites in the United States, Chile, and Peru.

The overall efficacy of 74% is lower than the results of the preliminary analysis of its results, which were released in March 2021. Then, initially, the drugmaker had showed that its vaccine was 79% effective in preventing coronavirus infections, but a day after the publication of the trial results, the US National Institute of Allergy and Infectious Diseases had released a statement alleging that AstraZeneca may have used “outdated information” that “provided an incomplete view of the efficacy data”. A week later, AstraZeneca updated it analysis stating that its COVID-19 vaccine was 76% effective at preventing symptomatic illness. This had marked a setback for the vaccine’s approval in the US.

A total of 32,451 participants underwent randomisation, in a 2:1 ratio, to receive AstraZeneca vaccine or the placebo (10,816 participants). In the fully vaccinated group, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the vaccinated group. Eight cases of Covid-19 were noted among the 8550 participants in the placebo group.

The majority of participants were men (55.6%) and had at least one coexisting condition (59.2%) and the mean age was 50. At least 79.0% of the participants were White, 8.3% were Black, 4.4% were Asian, 4.0% were American Indian or Alaska Native, 2.4% were of multiple races or ethnic groups, 0.3% were Native Hawaiian or other Pacific Islander, and the remainder were of unknown or unreported race or ethnic group. Across both groups, 22.3% of participants were Hispanic or Latin, stated the paper.

After the first AstraZeneca shot, there were 119 serious adverse events amongst 101 persons and 59 events among 53 participants in the placebo group. During the entire trial period, seven adverse events led to deaths of 7 participants in the vaccine group, and nine adverse events led to 7 deaths in the placebo group. However, no deaths were considered by investigators to be related to the vaccine or placebo.

The paper pointed out that the estimated vaccine efficacy was high against symptomatic illness in participants between 18 and 64 years of age was 72.8 and those above 65 years of was 83.5% and was consistent across participants of different races and ethnic groups even with coexisting conditions, including high blood pressure, history of smoking, asthma, type 2 diabetes, severe heart conditions and liver disease.

In Chile, four cases of symptomatic illness were noted among 1,360 participants in the AstraZeneca group as compared with two among 672 participants in the placebo group. In Peru, 11 cases among 867 participants in the AstraZeneca group and nine cases among 435 participants in the placebo group were observed. The study observed an estimated vaccine efficacy of 73.7% against symptomatic Covid-19 regardless of evidence of previous SARS-CoV-2 infection.

The US study asserted that there were no cases in either group of thrombosis (blood clotting in a blood vessel which can lead to a stroke or pulmonary embolism) with thrombocytopenia, cerebral venous sinus thrombosis, or venous thrombosis in unusual locations in either groups.

The Serum Institute of India’s phase 2/3 bridging trial results also observed there were no thromboembolic-associated or autoimmune-related SAEs among the participants.

In August 2021, Serum Institute of India, which is manufacturing Covishield after technology transfer from AstraZeneca, had stated in a pre-print paper that Covishield has a ‘non-inferior’ immune response compared to the Oxford AstraZeneca vaccine. The study had claimed that claimed that 98% of those who got both doses of Covishield developed immune response, while 98.9% of the participants who got two doses of AstraZeneca developed an immune response.

In June 2021, AstraZeneca had published that the sub-analysis of the vaccine trial in UK demonstrated vaccine efficacy of 70.4% preventing symptomatic COVID-19 against the Alpha variant, when measured more than 14 days after a second dose.

In November 2020, the company announced that AstraZeneca vaccine was 70.4% effective at preventing symptomatic COVID-19 occurring more than 14 days after receiving two doses of the vaccine. A further analysis of the efficacy, said a statement from the company, showed that when the vaccine was given as two full doses, vaccine efficacy was 62.1% in participants who received a half dose followed by a full dose.

AstraZeneca vaccine’s effectiveness is lower than the 96% efficacy with two doses of Moderna vaccine and 89% with two doses of Pfizer vaccine. However, both these vaccines are not available in India, where only Covishield, Bharat Biotech’s Covaxin and the Russian Sputnik have been made available.