EMA authorizes AstraZeneca COVID-19 vaccine

Regulatory NewsRegulatory News | 29 January 2021 |  By 

The European Medicines Agency (EMA) on Friday recommended a conditional marketing authorization for AstraZeneca's vaccine against COVID-19, developed in conjunction with the University of Oxford.
Said EMA’s Executive Director Emer Cooke in a press conference announcing the authorization, "We have further expanded the arsenal of vaccines available to EU... to combat the pandemic and protect their citizens."
EMA’s third COVID-19 authorization was given on the strength of four randomized, double-blind placebo-controlled trials conducted in the United Kingdom, Brazil and South Africa that enrolled about 24,000 patients in total. EMA is using a rolling review strategy for COVID-19 vaccines. 
All four studies were used by EMA to assess the vaccine’s safety. However, the regulator calculated efficacy looking at just two of these trials, the UK and Brazil studies. This was done, said Bruno Sepodes, vice chair of EMA’s Committee on Human Medicinal Products (CHMP), because of two reasons. First, said Sepodes in a press conference announcing the decision, there were few cases of COVID-19 in the other two studies, limiting interpretation of effectiveness. Second, the dosing regimen in the other two trials, in some cases, fell outside the 4 to 12-week window AstraZeneca had set as the standard interval.
This is also the interval recommended by EMA. “The reason we chose this interval was because when looking at the two trials we based our opinion on, 86% of patients had a dosing interval between 4 and 12 weeks,” said Sepodes.  Though estimates of vaccine efficacy vary depending on which of the four studies are included for analysis, EMA agreed with AstraZeneca’s analysis that the vaccine resulted in an approximate 60% reduction of symptomatic cases of COVID-19.
In addition to variation in dosing intervals, some UK trial participants received an initial dose of the two-dose regimen that contained about half the vaccine intended. This occurred because of variances in calculation methods used for measuring dose strength. Higher vaccine efficacy was seen in an interim analysis among individuals who received the low dose/standard dose regimen, to the surprise of many, as detailed in a December 2020 Comment in The Lancet.
However, in a 27 January meeting of the CDC’s vaccines advisory committee, AstraZeneca representatives provided an alternate explanation to the mystery of the mixed regimen’s efficacy: “Longer dose interval was associated with increased spike-binding antibody response in participants seronegative at baseline,” read the title of a backup slide the firm produced in response to questioning from the committee.
The slide’s data indicated that, in fact, most of the low dose/standard dose recipients had received their vaccines at an interval ranging from 9 weeks up to 12 weeks and beyond. The geometric mean titers for spike-binding antibodies for the mixed-dose recipients were almost identical to those for standard dose/standard dose recipients who also received their second dose 9 weeks or more after the first. These data, said AstraZeneca officials, made it likely that the low dose effect was a red herring.
Sepodes, along with Marco Cavaleri, EMA’s head of biological health threats and vaccines strategy, took questions from the press after Cooke, announced the regulator’s conditional authorization of the vaccine.
Cavaleri, in answering questions, noted that immunogenicity levels for fully vaccinated participants have been uniformly robust across age levels for AstraZeneca’s adjuvanted chimpanzee adenovirus vector vaccine.
The studies used by EMA provide only limited information about how well the vaccine will work in individuals over the age of 55, acknowledged Sepodes. However, “We are still recommending its use in this age group,” he said. “At least some protection is expected in this age group, although the exact protection with this age group cannot be estimated at the time being.”
The regulators pointed out that EMA will be conducting its own postmarketing studies to track how the vaccine performs in the elderly as well as a number of other potentially vulnerable subgroups. These include pregnant and breastfeeding women, as well as immunocompromised individuals. “We have limited data on pregnant women… taking into account that pregnancy itself is a risk for severe COVID-19, the vaccine may be considered on a case-by-case basis” for this population, said Sepodes. “We have no data for breastfeeding women but based on preclinical studies we do not anticipate any risk” for breastfeeding infants, he added.
EMA officials said they will also turn their attention to anticipated results from the US Phase 3 clinical trial of the AstraZeneca vaccine. This trial, together with other incoming data, means that the regulator will have access to evaluable data from an additional 30,000 participants during the first quarter of 2021.
A pediatric investigation plan will set parameters for an anticipated clinical trial of the vaccine in those under 18 years of age.
Separately, EMA announced today that an ongoing independent review of the safety of the previously authorized Pfizer-BioNTech messenger RNA COVID-19 vaccine shows no new concerns. The update is the first of planned monthly updates. In a press release, EMA directly addressed concerns of the deaths of some frail individuals after receiving the vaccine, called Comirnaty.
EMA’s safety committee “carried out an analysis of the cases and took into account the presence of other medical conditions and the death rate for corresponding age groups in the general population,” according to the press release. The committee “concluded that the data did not show a link to vaccination with Comirnaty and the cases do not raise a safety concern.”


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Tags: coronavirus, EMA, EU

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