The MHRA is continuing its rolling assessment of the coronavirus vaccine from the US drug company Novavax after the company reported it was effective against the UK variant with an overall efficacy of 89.3%.
The phase 3 UK trial in collaboration with the National Institute for Health Research (NIHR) vaccine registry involved 15,000 participants aged 18-84, with 27% aged over 65.
There were 62 positive cases, 56 of them in the placebo group. Half the cases were the UK variant of the virus.
Of the 62 cases, 61 were mild or moderate, and one in the placebo group was severe.
Post-hoc analysis found the jab was 95.6% effective against the original strain of COVID-19 and 85.6% effective against the UK variant strain.
The UK has ordered 60 million doses which will be manufactured in Billingham, Stockton-on-Tees. Deliveries could begin in the second half of the year.
Vaccine Taskforce Chair, Clive Dix, said: "These are spectacular results, and we are very pleased to have helped Novavax with the development of this vaccine. The efficacy shown against the emerging variants is also extremely encouraging. This is an incredible achievement that will ensure we can protect individuals in the UK and the rest of the world from this virus."
In the South African phase 2b of the trial in which 90% of cases involved that country's variant, efficacy was 60% in the 94% of the study population that was HIV-negative. The vaccine was not tested against the Brazilian variant.
The vaccine can be stored at 2-8C.
Paul Heath, professor of paediatric infectious diseases and director of the Vaccine Institute, St George’s, University of London, was principal investigator of the UK arm of the trial. He's been speaking and taking questions at a news briefing hosted by the Science Media Centre.
This is a large trial - 15,000 participants - so the largest COVID-19 vaccine trial in the UK and it started back in September, recruiting participants over a 2-month period. So fully recruited by the end of November, and 33 sites across the UK, so England, Scotland, Wales, and Northern Ireland, have been participating in this trial and have done a huge amount of work.
And all of this done through and with the support of the NIHR (National Institute for Health Research), the research arm of the NHS, and indeed with the great support of the UK Vaccines Taskforce.
The vaccine itself is a fairly simple vaccine platform vaccine technology. It's a subunit protein adjuvant vaccine. The subunit protein is a protein derived from the SARS-CoV-2 virus, and that is the spike protein.
And particularly key is to induce neutralising antibody immunity against this spike protein. And this is of course, what this and the other vaccines are doing.
It's combined with an adjuvant, an adjuvant being a substance to improve and enhance the immune response. So it's a simple vaccine. And if you like if we think about the influenza vaccine, that too is a subunit protein adjuvant vaccine, and there are others that we use routinely that are using this vaccine technology. So as opposed to the RNA and the viral vectored vaccine platforms that we're all becoming familiar with…this is more traditional vaccine technology.
The vaccine was given to 15,000 participants, half of whom received the vaccine, half of them received a saline placebo. It's a double blind, placebo controlled, randomised controlled trial with the endpoint being symptomatic, PCR-proven COVID-19 disease.
The interim analysis was to be done when around 50 cases had been reported in the trial. And that is where we got to in fact, by the time the interim analysis of the data came together, there were 62 cases in the trial.
And of course, what it has shown us is that cases of disease are extremely uncommon in vaccinated participants. There were 56 cases in the placebo group, and six in the vaccine group. So the overall vaccine efficacy is 89%, which is really high.
People will be familiar with the confidence intervals around such estimates and the lower end of that confidence interval is 75%, which means in theory that the efficacy won't be any less than 75%, which is extremely high.
This is great news of course. With that, we also know that there are no safety concerns.
Such things as medically attended adverse events and serious adverse events were no different between the vaccinated group and the placebo group, and this is really important.
This is interim data, around half of the participants have had 2 months of follow-up, which was the necessary level before these results could also be reported.
The full analysis is to come. Full analysis will be based on around 100 cases, and in fact that is almost there. So, in the next couple of weeks, we will reach that point and then the full data can be reported. And we will be doing that in a peer reviewed journal publication. But clearly, we expect that the efficacy will be pretty much the same as what we've seen here but there will be much fuller detail, of course, when we have that full analysis.
One of the things we set out to do when we were recruiting participants was to ensure that we had at least 25% of participants who were over the age of 65, because we all recognise how important that group is with COVID-19. And in fact, 27% of the participants were over the age of 65. So in the full analysis we will be able to report the cases of disease and other aspects, such as the safety in that older group as well.
I think the other really important piece of news…was that of the new variants, because of course, particularly in the last month or 2, we've been very aware that the majority of cases that are occurring in the UK, and certainly in certain parts of the UK, and therefore in trial recipients, in vaccinees, was this new UK variant.
And of course, we had reason to be concerned that the vaccine may not be quite so good against that variant. But in fact, the trial has really shown us that that is not a problem for the vaccine. The vaccine efficacy is pretty much the same, regardless of whether it's the new variant or the strain of the virus that we were dealing with before.
So this is also really good news, really important.
I think it tells us that though new variants are occurring, and of course they will continue to occur, this is the nature of the virus, it does not necessarily mean that they will have a significant impact on our vaccines.
Now, having said that, I think people are also familiar with the fact that the phase 2 data from the South Africa trial was also reported at the same time. And this also showed very good efficacy against disease in South Africa. The efficacy was lower, and of course, that will largely be a reflection of the South African variant which again dominated in that trial.
So there is an impact of the South African variant on efficacy. But nonetheless, this is still an effective vaccine with the South African variant.
The nature of this vaccine, and indeed the other vaccines that we now have available to us, be it the RNA vaccines or the adenovirus vectored vaccines, is that they can be adapted. And Novavax and indeed, the other vaccine manufacturers, are in the early stages of looking to adapt vaccines if required. And I know that Novavax are doing that, looking particularly at the South African variant.
The vaccines can be adapted relatively quickly. And that's really important because it means that we can then stay ahead of the virus and continue to have vaccines that will be effective and drive these disease rates down.
This…is a feature of all these vaccines that we now have available to us, which is a really positive thing and means that we can be optimistic and there is a lot of light, I think now, at the end of the tunnel, which is what we want, which is what we need.
Did you do any regular PCR testing to look at whether the vaccine prevented transmission?
The approach taken is to do that based on antibody responses. Over the course of the trial…all participants are followed for 12 months after that second dose, they have regular blood tests. Those blood tests are looking for seroconversion to the virus using an antibody…and that means we will be able to determine whether any of the participants have had infection but were asymptomatic because if they were symptomatic, they would have reported it to us and we would have taken swabs. We don't have those data as yet but of course, we will have those data ultimately.
Do the two doses have to be 3 weeks apart?
Two doses given 21 days apart…is the schedule that was used in the trial.
We know there's great interest in knowing about the efficacy of one dose. And fairly soon we will know that too, because, of course, we do know that cases occurred between dose one and dose two in the trial. I very much hope that most of those cases were occurring in the placebo recipients rather than the vaccinees. But I don't even know that yet. So we will know about the ability of the vaccine to protect after one dose up until that second dose 21 days later. But of course, in this trial, like with all the trials, though, 0 and 21 was the schedule, we definitely know that many, many participants, for various good reasons, were not able to receive that second dose exactly on time. It may have been a week late. In some cases, it may have been many weeks later, and in some cases, they didn't receive the second dose. So all of these data are important for us in trying to understand and trying to be a bit more precise about the efficacy of one dose.
Certainly, with a standard vaccine like this, I would have very little concern about extending the interval between doses.
Will over-65s be unblinded and be given the choice to have a licenced vaccine?
One of the big challenges for us in running this trial and indeed for other COVID-19 phase 3 vaccine trials in the UK, is the fact that of course, the Pfizer and the Oxford/AstraZeneca vaccines have now been licenced and have been rolled out.
And of course, this is a challenge because many of the participants in our trial have become eligible for these licenced vaccines. But a basic principle of the trial was always that if any of the participants become eligible for a licenced vaccine, then, of course, they have the option of going on and having that vaccine.
So we have not been stopping that at all.
As soon as vaccinees in the trial are given an appointment for their licenced vaccine… then they make contact with the trial team, the trial team then unblind them, and if they have received the placebo, and of course half of them have, then they are then encouraged to go and get the licenced vaccine.
They have also been encouraged to stay in the trial. And this is important because it does mean we can still continue to gather information about the safety of the vaccine.
Will participants who had the placebo be offered the Novavax vaccine, or will it just be the one that they're offered that's been deployed?
This is a discussion that we're having with Novavax at the moment. And it's indeed possible that what will happen is that participants in the trial who have received placebo will be crossed over and receive the active vaccine, and that potentially all of that will still be done in a blinded way. Which means that the trial can still report safety and efficacy in a robust way. So a double blind crossover trial is being considered at this moment.
And I would hope that that will be what we do. That will provide confidence to all of the participants in the trial that they have received what is now known to be an effective vaccine.
I just add though, many of those over the age of 65, of course, in the meantime, are being unblinded and given the licenced vaccine as it is being rolled out in the UK.
Is research being done into the prospect of a 'mix and match' approach with different vaccines?
There is a separate study that is starting in February called the Con-COV trial led by my colleague, Professor Matthew Snape in Oxford, which is addressing the Pfizer vaccine and the Oxford/AstraZeneca vaccine in different combinations, as well as looking at the interval between the two doses.
I would like to think that when the Novavax vaccine receives a licence from the MHRA that too will be incorporated into that programme of work to see whether the mixing of this vaccine with other vaccines is immunogenic and safe, because this may be a good way of…improving the response, of covering variants potentially better and also reflecting the reality of a large vaccine programme where mixing might happen inadvertently. Knowing that that is a safe and similarly effective thing to do will be really important.
What are the implications for immune compromised people?
Of course, those who are very immunocompromised have not been in these trials. They were not included in the phase 3 trial for a range of reasons. So one has to be careful in extrapolating to that.
What I can say is, though, that this is a protein adjuvant vaccine. There is no virus in it. It will be safe for immunocompromised, even those people who are very immunocompromised, there's no concern about it causing disease. So I would have no concern about the safety of the vaccine in those people.
I would like to think that the high neutralising responses that were seen in the phase 1/ phase 2 studies would also be seen in them, perhaps to a lesser extent, but that may not be important because we don't know how much immunity is required to prevent disease and if it's relatively low, then...these vaccines are inducing such high levels that they are likely to be protected in them. Those studies need to be done. And you know, they're gearing up to be done addressing the vaccine immunogenicity in these special groups. I think we can be optimistic.
What can you say about the role of the UK Government and the Vaccines Taskforce in bringing Novavax, an American biotech company, to the UK and setting up the clinical trial here?
Huge foresight, I think.
This happened very early on in the development programme for all of these vaccines…the Vaccine Taskforce identified candidates that looked very promising, they identified candidates using a range of different vaccine technologies, because it wasn't clear at all, which ones would be effective. I think that showed huge foresight.
The investment then, in bringing those vaccines, and then providing a platform for high quality research through the NIHR (National Institute for Health Research), that I think was attractive to all of these vaccine companies and provided them the confidence to bring their vaccines to the UK, and then be tested in a rigorous way.
So all of that meant that we were in very early with these vaccines, including the Novavax vaccine. I think that the result of that is we're now here today announcing the phase 3 trial efficacy data for this vaccine for the first time.
I think it is a tribute to the Vaccines Taskforce and to the NIHR, and, of course, all of my colleagues, my research colleagues around the country and to the participants in taking part in this and all of the other COVID-19 vaccine research that is underway in the UK.