November 30, 2020

expert reaction to announcement by Moderna that they have concluded the primary efficacy analysis for the Phase 3 study of their COVID-19 vaccine candidate

Moderna have announced that they have concluded the primary efficacy analysis for the Phase 3 study of their COVID-19 vaccine candidate and are planning to request  Emergency Use Authorization (EUA) today from the U.S. FDA.

Dr Penny Ward, Visiting Professor in Pharmaceutical Medicine at King’s College London and Chair of the Education and Standards Committee of the Faculty of Pharmaceutical Medicine, said:

“The press release today provides additional information from a completed analysis of the Moderna mRNA vaccine program, which further confirms the efficacy noted in the preliminary analysis completed earlier in the month. It is particularly encouraging that no severe cases were documented among vaccinees while 16% of disease episodes in the placebo group were considered severe. Prevention of severe disease and hospitalisation can be expected to significantly reduce pressure on overstretched health services, provided that a sufficient proportion of the high risk population can be vaccinated. The protocol was not designed to demonstrate impact of vaccination on asymptomatic infection, or on transmission of disease from a vaccinated person to others and so the potential to use this vaccine for outbreak control cannot be estimated. It would also be helpful to have some information on the genetic similarities (or otherwise) between virus causing disease in placebo and vaccine recipients.

“Given similar outcomes in earlier reports from trials of other vaccines, the sustained effect noted suggests that we may be able to expect similar outcomes in other ongoing phase III trials, meaning that a range of vaccines may soon be available to deploy across the world. We will need them all.”

Prof Deborah Dunn-Walters, Chair of the British Society for Immunology COVID-19 and Immunology taskforce and Professor of Immunology at the University of Surrey:

“Today’s announcement from Moderna provides further information on the results from their phase 3 trial for the mRNA-1273 vaccine against COVID-19. While the reported vaccine efficacy of 94.1% is very positive news, we still need to see the complete dataset to be able to accurately assess the full results and implications.  The fact that no serious cases of COVID-19 were reported in the vaccinated group should be a cause for optimism. We await the full trial results with anticipation.”

Dr Gillies O’Bryan-Tear, Chair, Policy and Communications, Faculty of Pharmaceutical Medicine, said:

“These results of the main efficacy analysis of the Moderna Phase 3 study confirm the results of the interim analysis: the vaccine was effective in 94% of recipients and prevented all serious cases. No serious side effects were reported and two months of follow up has now been completed.

“Moderna gave more details than the interim analysis: amongst 196 cases, 185 occurred in the placebo group and 11 in the vaccine group. Efficacy was reported as consistent amongst the 33 older (65+) adults and 42 from diverse backgrounds, although the numbers would probably have been too small in these groups to reach statistical significance.

“Moderna are submitting their data for emergency authorisation with both the FDA and European Medicines Agency imminently and have indicated that the FDA will review the data on 17 December.

“Although we await the full details of these results in published form, we can now assume that this vaccine will be approved for use in December. Separately the UK authority the MHRA had announced that they are reviewing the data on an ongoing basis, and it’s likely that approval will also be granted within a fortnight, using emergency authorisation procedures.

“Moderna has announced the distributor, McKesson, and has made available 20 million doses in the US this year; the U.K. has secured 5 million doses, enough for 2.5 million people.

“Although the U.K. will not receive many doses of this vaccine, realistically it may be enough for 2020 since, separately, the government has announced it plans to vaccinate 1m people per week. Moreover, we are expecting similar announcements imminently from both Pfizer/BioNTech (from whom we have secured 50 million doses this year and next) and Oxford Astra Zeneca.

“As the vaccine programmes begin to roll out, attention will turn once again to operational issues, but the nation will breathe a sigh of collective relief as the numbers of people vaccinated rolls in.”

Dr Alexander Edwards, Associate Professor in Biomedical Technology, Reading School of Pharmacy, University of Reading, said:

“This is great news indeed- the more trial data that we have, the greater confidence we have that vaccines can be used to blunt the human cost of COVID-19. As the numbers of cases reported grows, confidence grows that this amazing protection will be maintained in a product that can be rolled out to protect the public.

“The most significant part of this news is that we should remember RNA vaccines are really new, and potentially have really significant advantages over some other older types of vaccines. Moderna have also recently announced improvements to the product stability, allowing normal fridge distribution for up to 30 days, and frozen storage in normal (-20) freezers, which will help with logistics.

“Overall, the many benefits of this type of “engineered” vaccine are going to become clearer- there are costs to innovation but major benefits. The manufacture of a vaccine based on blending biosynthetic RNA with lipids to make tiny particles is not currently routine, which may explain why it is currently reported to be more expensive than vaccines based on viral vectors. This is the upfront cost of innovation. But as more RNA vaccines are made, and the production scales up from clinical trial material to mass-manufacture, we should very rapidly improve the manufacturing process and it should become cheaper, faster and possible to produce all over the world in the near future. We might expect other RNA vaccines to become available against other infections, and this experience can only make it faster to respond to new threats. Once the first products become widely used, investment in manufacture will drive more innovation and transform production.

“Of course, we still need to see full data sets published in reviewed journals, and regulators will pore over every detail- and vaccine rollout remains a mammoth exercise- but overall, the more vaccine trial data we have, the closer we are to a major new phase in the pandemic.”

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

“These revised findings are very much in line with those previously announced by Moderna. This is essentially good news, in that there continues to be a very high level of observed effectiveness, with this effectiveness was consistent across older populations and ethnic minorities.  There were also no serious adverse events caused by the vaccine. We must of course reserve a little caution as we await the final published results, but for now we can retain the existing optimism that this new generation of vaccines may be deployed in the near future.”

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

“These results are essentially identical to those announced on November 16th, with a few more details. In my comment on November 16th I noted that it was important not to pay too much attention to the exact percentage value of the efficacy. While the best estimate is 94.1% against all Covid-19 disease, the statistical uncertainty in this is such that the data are compatible with a true efficacy of about 87%. This is of course, still a very good efficacy. Similarly, the 100% efficacy against more severe disease is compatible with an efficacy of 90% again, this is very good and is some evidence that severe as well as mild disease is prevented.

“There seems to be no evidence that efficacy is worse at older ages, though with only a total of 33 aged 65 and over, the uncertainty in these results on their own is considerable. The results from blood tests examining immunity may give a better idea of whether the vaccine truly is just as efficacious at older ages as at younger ones, but so far this is again encouraging. The relatively minor adverse reactions, which are greater after a second than a first dose, are not a real concern. The absence of unexpected severe reactions in 15,000 approximately, who have received the vaccine is very good news also. This means that reactions that occur in more than 1 in 5,000 vaccinated are unlikely to occur. Rare adverse effects will only be seen after a million or so people have been vaccinated, and it will be important to both be vigilant for these but also not to attribute coincidental events to being caused by the vaccine. Careful follow-up studies will be necessary.”

Prof Azra Ghani, Chair in Infectious Disease Epidemiology, Imperial College London, said:

“The primary analysis results released today confirm the data reported in the interim analysis demonstrating high efficacy of the Moderna vaccine against COVID-19 disease. The company also today report high efficacy against severe outcomes with none of those in the vaccinated arm developing severe disease. Whilst this does not exclude some risk of severe disease after vaccination given the relatively small number of severe cases, these results suggest very high efficacy (>85%) against this endpoint.

“The results have been tested across a diverse population and are reported as being consistent in different sub-groups although these numbers are not given and we should wait for further information in the scientific article that is being prepared. Although not yet reported, the trial includes a secondary endpoint of asymptomatic infection – efficacy against this would be very welcome as it would give the first indication of the broader indirect impact that widespread vaccination could have in reducing onward spread.” 

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

www.sciencemediacentre.org/tag/covid-19

Declared interests

Dr Penny Ward: “No COIs. I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development.  Until July 2019 I was Chief Medical Officer of Virion Biotherapeutics, which was a company developing broad spectrum RNA therapy for the treatment/prevention of respiratory virus infections.  Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases.  Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody).”

Prof Deborah Dunn-Walters: “No conflicts of interest”

Dr Gillies O’Bryan-Tear: “No conflicts.  Former Head of Vaccine Clinical Development, GSK.  I am a pharmaceutical physician, semi-retired and have worked in a variety of fields, including oncology (cancer) drug development and vaccines development.  I have not been active in vaccine research for many years and have no current interests in or conflict with any of the Covid-19 vaccine research programmes.”

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.”

Prof Azra Ghani: “I am providing advice to WHO and WHO-Europe on vaccine modelling to support allocation.”

Dr Al Edwards: “I don’t work on current COVID vaccines nor have any commercial vaccine activity.”

None others received.