The announcement of a 90% effective vaccine by Pfizer and the German company BioNTech has raised the prospect that beyond the second wave of Covid-19 infections a solution to return to normal life is on the horizon.
According to the World Health Organization (WHO) there are more than 300 vaccine candidates in development, with around 40 in human clinical trials. Ten of these have reached the phase 3, the final stage of testing needed before approval for use in the general population.
Approval at 50% efficacy
The WHO and the US organisation that approves vaccines, the FDA, have determined that the minimum criteria for approval of any Covid-19 vaccine is a 50% level of efficacy.
Although 50% efficacy means that 50 out of a 100 people given the vaccine will get the disease, which doesn’t sound that good, it is hoped that those that do get the disease will get a milder form, meaning less people in ICU and less deaths. This is the situation with the current influenza vaccines; some people do get flu but it is a milder form.
Each current phase 3 trial involves a group given the vaccine (in most cases in two doses) and a control group given a placebo. None of the participants are aware if they are receiving the vaccine or a placebo – this is known as a ‘blinded trial’.
All of the current phase 3 trials are what are known as ‘event-based’. This means that the trial ends and the data is analysed when a certain number of people across both the vaccinated group and the placebo group have contracted the virus and shown symptoms, this number is the trial endpoint.
This ‘event-based’ endpoint is used because although the perfect endpoint is complete prevention of infection, this has never been achieved for other coronavirus or influenza strains. Professor Andrew Pollard, who is leading phase 3 trials of the AstraZeneca vaccine, has noted that the major thing that is needed from a vaccine is to stop people being admitted to hospital, going to intensive care and dying.
The UK government, via its Vaccine Taskforce, has invested heavily in a vaccine portfolio and has pre-ordered doses across six leading vaccine candidates. The UK’s Vaccine Taskforce has options to purchase sufficient doses of each vaccine type to vaccinate a proportion of the UK population. The UK is reported to be one of the highest investors in vaccine development along with the US, Canada, Japan and the EU.
As the vaccine trials need to enrol thousands of people, the UK government has also launched the National Health Service COVID-19 vaccine registry, which by October had enrolled over 295,000 volunteers.
Of the six vaccines that the UK has options for, three are currently in phase 3 trials.
This vaccine is the leading vaccine, having almost completed a phase 3 trial that has enrolled over 42,000 participants across a number of countries. Initial results were reported in early November.
The vaccine is being developed by Pfizer and the German company BioNTech. On 9 November they reported the first data from the phase 3 trials, which found the the vaccine 90% effective, a far better result than experts had hoped for. The companies also reported that there had been no serious side effects. Now the trial will continue until there have been 164 confirmed cases, which means that there may be a reduction in efficacy in the final analysis.
When the final safety data is collected, which will take until the third week of November, according to Pfizer, then the data will be submitted to regulators for approval. There is a possibility with fast-track approval that doses of the vaccine could be given before the end of the year.
However, it has been noted that release of results in this way via press release, rather than peer-reviewed journal, is not usual. The BMJ reported that although experts have welcomed the news, they also emphasise how important it is to see the full results, which will include details such as the participants’ demographic details, including age and ethnic group, and the severity of the cases reported in the trial. Furthermore, the 90% efficacy reported is an estimate of short-term efficacy based on seven days of follow-up of participants after they were given the second dose. There is as yet no data on long-term efficacy; trial participants will be monitored for two years from the second dose to give data on safety and long-term efficacy.
Pfizer is producing the vaccine at a plant in Belgium and should have 100 million doses of the vaccine for delivery by the end of 2020. The UK has pre-ordered 40 million of those doses. As two doses of the vaccine are required to stimulate an immune response against the coronavirus, that would be enough to vaccinate 20 million people.
There was widespread positive media coverage of the reporting of the initial results, with many trumpeting a vaccine by year end, however Health Secretary, Matt Hancock, speaking at a press conference was more cautious, stressing that “we are not there yet”. He also noted that full safety results are not out yet, and if these weren’t good then the vaccine would not be rolled-out in the UK.
The roll-out of the vaccine will be a major undertaking – it needs to be given in two doses and to be stored at -70C until the last few hours before administration. The storage temperature is unusual in a vaccine and may cause some logistical problems.
Hancock states that he has asked the NHS, supported by the armed forces, to be ready for a roll-out at the start of December. The first populations to receive it will be people in care homes, elderly people and social care staff.
This is one of the most advanced vaccines worldwide, and the most advanced vaccine that the UK has an option on; it is nearing the end of phase 3 trials. It was originally developed by Oxford University and its spin-off company Vaccitech, but is now being developed with the pharmaceutical company AstraZeneca.
In July, Oxford University researchers published the results of an initial clinical trial, which showed that the vaccine induced strong immune reactions in the participants.
One hiccup came in October when the phase 3 trial was put on hold due to a participant developing adverse effects, but it was very soon restarted.
This is the vaccine that the UK government appears to be pinning its hopes on for a rollout in late 2020/early 2021. In early November, Simon Stevens, head of NHS England, said the NHS was preparing in case a vaccine was available before Christmas, with the first to be vaccinated being the over-85s and frontline health workers.
However, Professor Andrew Pollard, head of the Oxford University group leading development, played down the chances of vaccinating people before Christmas in his evidence to a joint hearing of the science and health committees, he said: “I think there is a small chance of that being possible, but I just don’t know.’
The level of efficacy is unknown at the moment as the results have not been unblinded and the data assessed, however Pollard was optimistic that this point will be reached before the end of 2020.
This vaccine developed by Novavax began phase 3 trials in the UK in September. Many of the participants will be taken from the National Health Service COVID-19 vaccine registry. Novavax will enroll 10,000 participants between the ages of 18 and 84 in the trial. Each trial participant will receive two doses.
The UK has options on three other vaccines in development with Janssen, GlaxoSmithKline/Sanofi and Valneva. Head of the UK Vaccine Taskforce, Kate Bingham, noted in an article in The Lancet that numerous phase 3 studies are planned to begin in the UK in 2020/21.
At roughly the same stage of development of Pfizer/BioNTech’s vaccine is Moderna’s vaccine. Although still in phase 3 trials the company has begun what is known as a rolling review of the data with the UK’s regulatory authority, the MHRA. The MHRA can launch an independent assessment of the vaccine using the information submitted by Moderna, and also accept new evidence as and when it becomes available, until the application is complete. This approach speeds up the final approval process for the vaccine. The UK government, however, does not have an option on this vaccine.
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