AstraZeneca announced Monday that a combined interim analysis of late-stage studies showed that the COVID-19 candidate vaccine AZD1222 had an average efficacy of 70%, increasing to 90% for a regimen that included initial immunisation with a half dose. The pooled data come from the COV002 Phase II/III trial in the UK and the COV003 Phase III study in Brazil.
According to AstraZeneca, the interim analysis included 11,636 participants who received AZD1222 and was based on a total of 131 cases of COVID-19, with the BBC reporting that there were 30 cases in people given the vaccine candidate. The company noted that the analysis met the primary endpoint, with an independent data safety monitoring board determining that it showed protection from COVID-19 occurring 14 days or more after two doses of the vaccine. In addition, there were no hospitalisations or severe cases of disease reported in subjects receiving AZD1222.
Further results showed that in 2741 people given a half dose of AZD1222 followed by a full dose at least one month later, the efficacy of the vaccine was 90%. Meanwhile, another dosing regimen tested in 8895 participants showed 62% efficacy when given as two full doses at least one month apart. AstraZeneca added that AZD1222 was well tolerated across both dosing regimens.
Andrew Pollard, chief investigator of the Oxford Vaccine Trial, said "we've found that one of our dosing regimens may be around 90% effective and if this dosing regime is used, more people could be vaccinated with planned vaccine supply." Although researchers do not know exactly why the half dose as an initial immunisation proved more effective, Pollard noted "we think that by giving a smaller first dose that we're priming the immune system differently – we're setting it up better to respond." He added that "what we don't know at this moment is whether that difference is in the quality, or the quantity of immune response, and that's something we're going to be digging into over the next weeks."
Pollard said that "those who got that regimen with higher protection, there's a suggestion that it was also able to reduce asymptomatic infection. If that's right, that means that we might be able to hold the virus in its tracks and stop it from transmitting between people." For further analysis, read ViewPoints: Nuances necessary when comparing the newest COVID-19 vaccine.
AstraZeneca indicated that it will now prepare submission of the data to regulatory authorities, whilst it will seek an emergency-use listing from the World Health Organization allowing for accelerated availability in low-income countries. The drugmaker added that full analysis of the interim results will be submitted for publication in a peer-reviewed journal.
The COV002 study includes 12,390 participants aged 18 years or over, who are healthy or have medically stable chronic diseases and are at increased risk for being exposed to the SARS-CoV-2 virus, while the COV003 trial has enrolled 10,300 similar subjects. In the COV002 study, people are randomised to receive one or two intramuscular doses of a half or full dose of AZD1222 or comparator, meningococcal vaccine MenACWY, while in the COV003 trial, subjects are randomised to receive two intramuscular doses of a full dose of AstraZeneca's vaccine or MenACWY as first dose and a saline placebo as second dose.
Clinical studies of AZD1222 are also being conducted in the US, Japan, Russia, South Africa, Kenya and Latin America, with planned trials in other European and Asian countries, and will include a total of up 60,000 participants globally.
AstraZeneca said that it is "making rapid progress" on manufacturing AZD1222, with operations executive Pam Cheng noting that the company expects to have 200 million doses by the end of the year, and 700 million doses ready by the end of the first quarter of 2021. The drugmaker added that it aims to have a capacity of up to 3 billion doses of the vaccine in 2021 on a rolling basis. Unlike mRNA vaccines being developed by Moderna and a partnership between Pfizer and BioNTech that require very cold temperatures for storage, AstraZeneca suggested that AZD1222 "can be stored, transported and handled at normal refrigerated conditions for at least six months and administered within existing healthcare settings."
CEO Pascal Soriot commented "the vaccine's simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available, supplying hundreds of millions of doses on approval." AZD1222, which was co-invented by the University of Oxford and its spin-out company Vaccitech, uses a replication-deficient chimpanzee viral vector and contains the genetic material of the SARS-CoV-2 virus spike protein.
Despite the positive results for AZD1222, shares in AstraZeneca fell as much as 4% on the news as the data drew comparisons from analysts and investors to those recently released by Pfizer and BioNTech, as well as Moderna. In Pfizer and BioNTech's Phase III study, a final analysis of 170 cases of COVID-19 recently showed that their mRNA-based candidate BNT162b2 was 95% effective at preventing infection with SARS-CoV-2. The companies last week also submitted an FDA request seeking emergency-use authorisation for the vaccine. Meanwhile, an interim analysis from the late-stage COVE trial of Moderna's experimental COVID-19 vaccine mRNA-1273 showed an efficacy rate of 94.5% based on 95 cases of coronavirus infection.
Commenting on the latest findings, analysts from SVB Leerink said AstraZeneca had not yet disclosed enough information about safety events that had forced it to temporarily halt Phase III testing of AZD1222, which has since resumed. They also noted that only a small number of people had received the smaller first dose of AZD1222 in the trials, while no information was provided on the number of COVID-19 cases in this group. In addition, analyst Geoffrey Porges suggested it was unlikely the vaccine would be approved in the US because the studies did not appear to meet US requirements for representation of minorities, the elderly and other high-risk populations. However, AstraZeneca indicated that it plans to seek clearance to modify the US trial in order to obtain more data on initially administering a half dose of AZD1222.
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