January 29, 2021

expert reaction to EMA recommending the Oxford/AstraZeneca COVID-19 Vaccine for authorisation in the EU

The European Medicine Agency (EMA) has recommended the Oxford/AstraZeneca COVID-19 Vaccine for authorisation in the EU for use in people from the age of 18.

Dr Melanie Saville, Director of Vaccine R&D at CEPI, said:

“We welcome today’s (29 Jan) announcement that the European Medicines Agency (EMA) has recommended granting a conditional marketing authorization for the University of Oxford/AstraZeneca COVID-19 vaccine.  The EMA has determined that the vaccine is safe and effective in adults over the age of 18 and as such this is an important milestone for vaccination efforts in Europe and beyond.

“With several approved vaccines now available, and more showing encouraging late-stage trial results, the world is in a stronger position to push back against COVID-19.  The Oxford/AstraZeneca COVID-19 vaccine can play a crucial role in the world’s response to this pandemic.  The evidence of its efficacy is robust, and it has been shown to prevent serious illness and death, which is a priority at this stage in the pandemic.  In addition, it is inexpensive to produce, and can be stored at 2-8 degrees Celsius – characteristics that will enhance access and make global distribution easier, especially in low-income and middle-income countries.  AstraZeneca’s commitment to sell their vaccine at no profit is also testament to their commitment to ensuring the whole world benefits from these scientific advancements.

“COVAX has established agreements with University of Oxford and AstraZeneca and other manufacturers that ensure that we have a clear pathway forward to securing 2 billion doses for the populations at greatest risk around the world, as they are manufactured and become available.  However, securing global vaccine supply is not the only challenge we need to overcome.  The emergence of virus variants, some of which might have the ability to evade vaccine protection, pose a very real threat to our progress and underscore the need to continue invest in vaccine R&D to stay one step ahead of this virus.”

Dr Peter English, Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“It has been disappointing to see some commentators assuming that “absence of evidence is evidence of absence”.  That, because there is little direct evidence of efficacy in recipients age 65 plus, for well-rehearsed and understandable reasons, this equates to evidence that the vaccine will be ineffective in this age group.

“Clearly, this is not the case.

“While in general vaccines are less effective in older people, there is indirect evidence that the Astra-Zeneca vaccine can be expected to be effective in this age group – evidence of good antibody and T-cell responses, similar in older people to in younger people.

“And it is important to understand the reasons for the relatively sparse data in this age group.  It is not because there is anything to hide; it is because the trial wanted to ensure there was no safety issue in younger people (in which any such issues were likely to be less harmful than in older people), so they tested it in younger patients first.  And it is because older people have fewer contacts with other people, partly because they have been cautious and taken sensible steps to reduce their risks, and as a result, it has taken longer to accumulate enough cases or infections in the older trial participants.

“Since the UK and many other countries are prioritising those most at risk – older patients; and because infection rates are still alarmingly high, post-marketing surveillance will soon provide extensive, good quality evidence of the efficacy of the vaccine in this age group.

“It should be remembered, however, that it takes up to 3 weeks for the full benefits of the first dose to be realised (and patients protected); and then it will take time – up to three or four weeks for vaccinated individuals who do so to become infected, to be admitted to hospital, and, to die.  The vaccine has only been in widespread use since the beginning of January, so it may take a few weeks before we can see significant effects from the vaccine.

“It is to be welcomed that the EMA has recognised the value of the “first dose first” approach, allowing the vaccine to be administered with an interval of up to 12 weeks between the first and second doses.”

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“The committee that has issued its advice (technically it is the European Commission that will make the decision) has representation from all member states and recommended by consensus a formal conditional marketing authorisation.  This acknowledges that there are limitations in the amount of data but that extra information is expected to be obtained from the company in the future.  This is in some ways similar to the emergency use authorisation which has been done in the UK.  They conclude “This means that the vaccine demonstrated around a 60% efficacy in the clinical trials.”

“They do not impose any limit in terms of age but do note the limitations in the clinical data that have been noted previously.  This again is similar to the UK conditions of use.  They say “There are not yet enough results in older participants (over 55 years old) to provide a figure for how well the vaccine will work in this group. However, protection is expected, given that an immune response is seen in this age group and based on experience with other vaccines; as there is reliable information on safety in this population, EMA’s scientific experts considered that the vaccine can be used in older adults”.

“This is in line with UK advice and practice.  The second dose is recommended to be given between 4 and 12 weeks after the first dose.  This allows for the UK position regarding spacing of doses.

“It was well-known that the clinical data for this vaccine were limited for those aged 70 and over.

“In the preliminary randomised trial data from The Lancet paper, it was stated there “As older age groups were recruited later than younger age groups, there has been less time for cases to accrue and as a result, efficacy data in these cohorts are currently limited by the small number of cases, but additional data will be available in future analyses.” It may be recalled that during the summer of 2020 in the UK (where the older people were largely recruited) there was a fall-off in cases of Covid which meant the data are necessarily limited.

“What is clear is that The Lancet paper made it clear that the blood test results (referred to as “immune response” in the quote from the EMA above) does not suggest that there will be notably lower efficacy at older ages for the Oxford/Astra Zeneca vaccine.  This was also true for the Pfizer and Moderna vaccines.  These vaccines show a similar pattern with increasing age in the blood test results to those from the Ox/AZ trial results.  The Pfizer and Moderna vaccines were conducted in a different situation meaning that they did have clinical evidence to back up the blood test results.

“There is no reason at all for anyone in the UK or elsewhere to think that this Oxford/AstraZeneca vaccine is ineffective at any age.  Its ability to be delivered to people in GP surgeries and care homes makes it a vital component in the attempts to reduce hospitalisation and deaths, especially in the elderly.”

Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:

“There is relatively little data currently available in the elderly from the phase 3 trials.  Therefore, the UK made a pragmatic decision to recommend this vaccine in older populations.  This was based on phase 2 data showing a strong immune response, and the limited phase 3 information that was available.

“These decisions are all in the context of a very high burden of COVID-19, and thus leaving vulnerable populations unprotected is in itself a risky decision at this point in time.

“The burden of COVID-19 disease is high across Europe.  Therefore, it is good to see the EMA recommend the use of the Oxford AstraZeneca vaccine in all ages groups, including older populations.”

Comments from scientists in the Oxford vaccine group:

Prof Andrew Pollard, Professor of Paediatric Infection and Immunity, and Chief Investigator on the Oxford vaccine trial, said:

“The recommendation by the European Medicines Agency is an important milestone in extending access to the Oxford-AZ vaccine in our region and providing further endorsement that the after rigorous scrutiny of regulators the vaccine can be used to help protect populations from the pandemic coronavirus.”

Prof Sarah Gilbert, Said Professor of Vaccinology, and Chief Investigator on the Oxford vaccine trial, said:

“It is excellent news that the European Medicines Agency has approved use of the SARS CoV-2 vaccine first produced in Oxford.  This decision paves the way to more widespread use of the vaccine to protect people against COVID-19 and gain control of the pandemic.”

Prof Adrian Hill, Director of the Jenner Institute, said:

“We have been working for the past 30 years at the University of Oxford to develop vaccines using novel technologies that can protect people around the world from diseases which claim many lives each year.  The work on ChAdOx1 nCoV-19 builds on many years of research by dedicated teams of researchers and clinicians, and we are delighted to see the European Medicines Agency joining the MHRA and other regulators in approving its use.”

https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-astrazeneca-authorisation-eu

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Dr Melanie Saville: “Nothing to declare personally (on an organisational level, Oxford/AZ COVID-19 vaccine has been funded in part by CEPI).”

Prof Stephen Evans: “No conflicts of interest.  I am funded (one day per week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them.  I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI.  I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs.  I am a participant in the Oxford/Astra Zeneca trial, and on 13th January 2021 learnt I had received the active vaccine.”

None others received.