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expert reaction to announcement of interim data analysis of the phase 3 Sputnik V COVID-19 vaccine trial

It has been announced that the Sputnik V vaccine against COVID-19 has demonstrated 92% efficacy in the first interim analysis from the phase 3 vaccine trials by the Russian Federation.

 

Prof Charles Bangham FRS FMedSci, Chair of Immunology, Imperial College London, said:

“These preliminary results provide further reassurance that it should be possible to produce an effective vaccine against COVID-19.  Whereas the Pfizer/BioNTech vaccine is based on RNA that produces the SARS-CoV-2 S (spike) protein, the Sputnik V vaccine consists of two doses, three weeks apart, respectively of two different human adenoviruses, each one expressing the S protein.  The Sputnik V strategy has some advantages, notably the less stringent need for cold storage, but the adenoviruses used are also likely to produce more side-effects such as fever or headache – although these are expected to be mild.  However, proper evaluation of the safety and efficacy of each of these two vaccines, the duration of protection, and their effectiveness in the elderly, must await publication of the full data on the trials.”

 

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

“The Gemaleya Centre in Moscow has today announced interim results from their phase 3 trial of the Sputnik V vaccine. The trial is planned to enrol over 40,000 patients, half receiving the vaccine and half placebo. This vaccine uses an inactivated adenoviral vector (a carrier) – a well established method used in gene therapy and cancer research for decades. The viral vector is used to carry DNA sequences coding for the spike protein of the Covd-19 virus into the body’s cells, which then generate the spike protein antigen using the cell’s own mRNA. This antigen is expressed on the cell surface where it can be recognised by the body’s immune system. This is a different type of vaccine to the Pfizer/BioNtech vaccine, although it targets the same part of the virus. The inactviated viral vector cannot replicate in the human body so poses little health risk.

“The press release states, “The trials evaluated efficacy among over 16,000 volunteers who received the vaccine or placebo 21 days after the first injection.” Elsewhere they say 16,000 had received two doses and 20,000 only the first dose. So it’s ambiguous, although the 16,000 number would imply that the analysis had been done only on patients who received two doses. Dosing intervals are sometimes 2 weeks with these vaccines so if that’s the case, the 21 day analysis point is consistent with an analysis of patients who had received both doses  – and that would make more sense as you need both doses for full efficacy.

“These interim results appear to be encouraging, in that over 90% efficacy has been reported – the exact breakdown of numbers has not been reported. However, only 20 cases of Covid illness were the subject of this interim analysis, in contrast to the 94 cases which were reported yesterday by Pfizer. Of note, Pfizer had initially planned an interim analysis on 32 cases, but after discussion with the FDA increased this to 60 – and ended up reporting on 94.

“However, despite these differences (and one cannot help speculating why the Gemaleya Centre chose to release data relatively early, one day after the release of the Pfizer data), the date are encouraging, and suggest this vaccine is also effective, although the numbers are too small to be sure of this yet. Like the Pfizer trial, asymptomatic cases were not looked for (at least, there is no mention that they were) so that conclusions about prevention of asymptomatic disease cannot be firmly drawn – although the Health Minister drew precisely this conclusion by claiming it will “stop the spread of coronavirus infection”. However, if the vaccine is effective against symptomatic illness, it is likely to be effective in preventing asymptomatic Covid also, as with the Pfizer vaccine.    

“Side effects were reported as pain at the injection site and a flu-like syndrome for a few days, as expected with this type of vaccine. No unexpected adverse events were reported, and no mention was made of serious side effects. 

“Interim analyses are commonly performed in clinical trials, but in order to protect statistical rigour, they should be pre-planned prior to the analysis of the results. The Gameleya centre did not provide the protocol so we do not know if this interim analysis was pre-planned, but in view of its small size, I would assume not. Although the lack of pre-planning could weaken the data package when it comes to a regulatory submission, if the efficacy is maintained at 90% or more, this will probably not matter much, provided the study has been well conducted and rigorously controlled. 

The Gamaleya Centre also report on 10,000 cases of additional patients who received the vaccine in an observational study. These were healthcare and front line workers. They report an efficacy rate of over 90% in this group also, although no details of how these results were obtained – for example whether there was a control group who did not receive vaccine, without which its impossible to calculate the efficacy rate. These data are therefore difficult to interpret and little weight should be attached to them until more details are known. 

“I agree with the conclusions in the press release that the more vaccines become available, using different mechanisms of action, the better for the control of the pandemic. These data should be welcomed, while we await a fuller dataset.”

 

Prof Paul Hunter, Professor in Medicine, UEA, said:

“The Russian Sputnik 5 vaccine uses an adenoviral vector and so it different to the Pfizer vaccine which is an mRNA vaccine but similar to the Oxford AstraZeneca vaccine in development. An advantage of the adenoviral vaccines are that they are likely to be much more stable at normal refrigeration temperatures than the mRNA vaccines. The analyses presented today are very early results based on just 20 confirmed infections so the exact efficacy remains uncertain until the final analyses. Nevertheless, these early results are consistent with the results of the Pfizer vaccine and so this is good news not just for the Sputnik 5 vaccine but for other vaccines in development. If the first two very different vaccines are producing about 90% effective then it does suggest that several effective vaccines will reach market in the coming months and if other vaccines are more stable then it will be easier to distribute them including into low income countries.”

 

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:

What is the Sputnik vaccine and how does it work?

“This vaccine is a viral vector vaccine which uses two different serotypes of human adenovirus as the vector providing the COVID virus genes encoding the spike protein. Preliminary information from the phase I/II studies with this vaccine were published in the Lancet and Russia started vaccinating the population with the vaccine as a result of the observed immunological response described in that publication shortly afterwards, as well as starting a Phase III trial.

Based on the information in the press release, what can we determine about the efficacy of the vaccine? Is there enough information available?

“The press release text is a little confusing such that we cannot easily determine the number of individuals that have received the vaccine/placebo from which the efficacy data are derived. The total number of reported cases is 20 and efficacy is said to be 92%, which suggests that perhaps 18 cases were observed in the placebo group and 2 in the vaccinated population. No safety information is reported, but the authors point out that adenovirus vaccines have been available for many years and that the safety of these vaccines is well understood. As with all viral vector vaccines, an immunological reaction to the virus vector may be seen, and 80% of humans can be expected to have pre-existing immune response to the adenoviral vector, particularly adenovirus 5. By using a second adenovirus strain for the second injection of the two injection course, the potential for this immune response to negate response to the second injection is avoided.

What is an interim analysis? Why are they done? Are they common for vaccine trials?

“As noted previously, interim analyses are common in vaccine (and other phase III) trials, and are conducted to assess potential futility (ie no response) and appropriate safety to continue to administer the vaccine to the very large subject number that participate in these trials.

Is this promising/ exciting?

“This is the first data to be announced for a viral vector vaccine and as suggested previously is reassuring and bodes well given the good immunological response to the Oxford University/ Astra Zeneca simian adenovirus vector vaccine.

Any other comments?

“Based on these two results from distinctly different vaccine technologies it seems that the immunological response noted in early phase trials reasonably predicts clinical efficacy in preventing disease. We still do not know whether there is any impact on the pattern of break through disease in vaccinated vs unvaccinated subjects and the impact, if any, on infection and transmission, which will impact the use of vaccines in populations.”

 

Prof Eleanor Riley, Professor of Immunology and Infectious Disease, University of Edinburgh, said:

“Whilst encouraging, I worry that these data have been rushed out on the back of the Pfizer/BioNtech announcement earlier in the week. The Sputnik data are based on only 20 cases of COVID-19 in the trial participants, compared to more than 90 cases in the earlier trial.

“This is not a competition. We need all trials to be a carried out to the highest possible standards and it is particularly important that the pre-set criteria for unblinding the trial data are adhered to avoid cherry picking the data. Anything less than this risks a public loss of trust in all vaccines, which would be a disaster.”

 

Prof Brendan Wren, Professor of Microbial Pathogenesis, London School of Hygiene & Tropical Medicine, said:

“The interim results of the Russian Sputnik vaccine Phase 3 trials mirror those of the Pfizer Phase 3 trials in terms of over 90% efficacy tested on over 40,000 humans. The main difference is that the vaccine technology platform used by the Russian group is a surrogate virus (Adenovirus, similar to the Oxford group vaccine) to deliver the SARS-CoV2 antigen in contrast to the Pfizer vaccine that uses mRNA. The advantage of this approach is that -80C freezing will not be required in the vaccine supply chain. Overall, this is more encouraging data confirming the early stage protection of a SARS-CoV2 vaccine using a different platform technology.”

 

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

“This is encouraging not just for this vaccine, but it is additional evidence that vaccines can be effective in Covid-19.

“This report refers to efficacy being assessed based on 20 cases. From the description it seems likely that 1 of the about 8000 people who had received the vaccine and had available data after two doses was compared with 19 people who received placebo (Assuming the allocation was split equally between vaccine and placebo).

“The consequence is that there is considerable uncertainty because of the small number (20) of total Covid-19 cases. Further follow-up is needed because the results are compatible with a much lower efficacy (60%) based on these data. The Pfizer results announced this week were based on 94 cases (probably split 8 on vaccine and 86 on placebo) so there is more certainty that the efficacy is likely to be above 80%. The Sputnik efficacy has also been estimated, though far less reliably than in the randomised trial, using a group without a comparator of 10,000.

“There seem to be no instances of serious adverse reactions to the vaccine. The full report should give more detail on how the follow-up was done and how the trial was monitored.

“Overall efficacy is about the same for these two vaccines, and while it is possible that favourable results are seen early, it is encouraging to see higher levels of efficacy than we might have expected based on experience with flu vaccines. We need to know how efficacy varies with age and this will require much more follow-up, and we also need to know how long protection from Covid-19 lasts.

“We will need as many different vaccines as possible to meet the whole world’s needs; it is no good just providing vaccines for high-income countries; low and middle-income countries will also ned protection.”

 

Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:

“Again, we can be cautiously optimistic that SARS-CoV2 vaccines targeting the spike protein are effective. Moreover, as the Sputnik antigen is delivered via a different modality, namely using a disabled Adenovirus rather than formulated RNA, this provides flexibility in terms of perhaps one or other method providing better responses in certain age groups, ethnicities, etc., plus the storage of this vaccine ought to be more straightforward.

“However, again it will be necessary to see the complete data set before making confident assessments of how well this, or other SARS-CoV2 vaccines work and full assessment of safety must be made. In particular, we must understand whether these prevent infection itself or just severe symptoms, as well as if vaccinees might continue shedding infectious virus. In addition, efficacy in different age groups, ethnicities and in patients with compromised immune systems will need to be determined before we can decide how best to deploy these hopefully world-changing medicines.”

 

Prof Ravindra Gupta, Professor of Clinical Microbiology, University of Cambridge, said:

“The interim announcement of vaccine efficacy for the Sputnik COVID-19 vaccine is welcome. The study uses a two dose schedule with a vaccine that produces the Spike protein in cells via a modified virus delivery system. The number of infections across placebo and the vaccine was only 20, and the data are preliminary. There is also the possibility that the human adenovirus system might be less effective in people with antibodies to this virus. However we have good reason to be optimistic as this vaccine does not need the -80C storage in contrast to the Pfizer RNA vaccine.” 

 

Prof Ian Jones, Professor of Virology, University of Reading, said:

“The Sputnik data is yet more good news for Covid-19 vaccine development. Although based on fewer cases than the recent Pfizer data, the vaccine looks as efficient and, like the Pfizer data, confirms and extends the earlier phase 2 results. We still need to know about the longevity of the response and the efficiency in different age groups, but the result bodes well for the other trials currently in progress and for having enough vaccine in geographically diverse regions to enable a comprehensive vaccination program on a global scale.”

 

https://sputnikvaccine.com/newsroom/pressreleases/the-first-interim-data-analysis-of-the-sputnik-v-vaccine-against-covid-19-phase-iii-clinical-trials-/

 

 

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

www.sciencemediacentre.org/tag/covid-19

 

 

Declared interests

Prof Charles Bangham: “No declarations of interest.”

Dr Gillies O’Bryan-Tear: “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 Paul Hunter: “No financial conflicts that I know of and I do not work in vaccine development or advise anybody on vaccines.”

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 Eleanor Riley: “Eleanor Riley is a member of the UKRI Covid-19 research taskforce and the UK Vaccines Network.”

Prof Brendan Wren: “No conflict of interests.”

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.”

Dr Stephen Griffin: “No conflicts.”

Prof Ravindra Gupta: “I have been involved in testing rapid diagnostic platforms for COVID-19. I am a member of the COG-UK consortium.”

Prof Ian Jones: “No conflicts.”

None others received.

 

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