UK Chooses Pfizer And Moderna For COVID-19 Boosters, But Questions Remain On Unpublished Trial Data
AstraZeneca's Vaccine Not Selected
Executive Summary
The UK’s choice of the mRNA vaccines as COVID-19 boosters is no surprise – but not releasing the key study data behind the decision is.
The UK government’s scientific experts have given the green light for booster COVID-19 vaccines for at-risk groups, using the Pfizer/BioNTech SE and Moderna shots.
The boosters could help the country reduce hospitalizations and deaths over winter, and avoid further lockdowns, but the decision is not without controversy – including questions about the data behind the decision, and why the main study on which it was based, the Cov-Boost study, remains unpublished.
Everyone over 50 years of age, and younger people with underlying health problems in the UK will be offered from this month either a full dose of the Pfizer/BioNTech vaccine or a half dose of the Moderna vaccine (as proposed by the manufacturer) at least six months after their initial prime-boost injections.
The recommendation from the UK Joint Committee of Vaccination and Immunisation (JCVI) in favor of Pfizer/BioNTech and Moderna is unsurprising given the high efficacy and excellent safety record of the vaccines so far, but leaves AstraZeneca PLC’s vaccine, the mainstay of the first wave of UK immunization, out in the cold.
The JCVI's Wei Shen Lim
The AZ/Oxford University product is recommended only where individuals cannot receive the mRNA vaccines, such as an allergy to either vaccine, but only when the person had received it for their first and second doses.
While observers might conclude that the decision not to use the AZ vaccine could be linked to its well-publicized but rare serious safety issues, and its slightly lower efficacy than the mRNA vaccines, the JCVI has not spelled out its reasoning. JCVI chairman Wei-Shen Lim simply said that for a “range of reasons including simplicity in delivery of the program we felt that overall, there was a preference for mRNA vaccines for the booster dose.”
The main basis for the decision was the UK government-funded Cov-Boost study, which examined a handful of different vaccines as booster jabs, but efficacy results from any of the vaccines studied have yet to be published. (Also see "UK Trial Could Help Pick Best Covid Vaccine Boosters" - Scrip, 24 May, 2021.)
The Cov-Boost study was launched in May, and was aimed at finding the best approach to boosting these initial immunizations. It included not only the authorized Pfizer, Moderna, AstraZeneca and Johnson & Johnson vaccines, but also the as-yet unauthorized jabs from Novavax, Inc., CureVac NV and Valneva SE. Cov-Boost examined whether a heterologous – or a ‘mix and match’ – approach might boost immune responses more than a homologous approach of following up with a third dose of the same vaccine.
The decision comes amid a heated international debate about whether COVID-19 booster jabs are needed at this time, and whether enough data are available to make regulatory decisions on their efficacy and safety.
Two US Food and Drug Administration officials and World Health Organization leaders spoke out in a Lancet editorial this week against booster programs which have begun in countries such as Israel and France, and could start shortly in the US – though friction between the FDA and the White House is evident. (Also see "Biden’s Trump Moment? COVID Booster Messaging Complicated After Top FDA Scientists Raise Doubts" - Pink Sheet, 13 Sep, 2021.)
The FDA experts, who will leave the agency in the fall, questioned the evidence base of the decision, saying there is little sign of significant decline in protection from the initial prime-boost schedules, and called for the priority to be developing countries, some of which currently have a vaccination rate as low as 2%.
This is eminently sensible and it is a little depressing to see us moving so quickly to what seem like non data-based decisions on boosting with 3rd doses in several developed countries. Considerations in boosting COVID-19 vaccine immune responses https://t.co/aF8WFsblIS
— Menelas Pangalos (@MenePangalos) September 14, 2021
Their views were echoed by AstraZeneca’s R&D leader Sir Mene Pangalos on Twitter who said it was “a little depressing to see us moving so quickly to what seem like non data-based decisions on boosting with third doses in several developed countries.”
JCVI Decision
A Public Health England report published on 9 September said data on the waning of protection from the vaccines against hospitalization were limited (and should therefore be treated with caution). Nevertheless, it said the available data suggested that the Pfizer vaccine remained 95% effective in preventing hospital admission beyond 20 weeks following a second jab. For the AstraZeneca vaccine, the data suggested protection against hospitalization declined to just under 80% after 20 weeks.
Lim said while such declines might seem small, they could have a big impact on the numbers of people being hospitalized in the coming months. He conceded that there was no certainty about whether or not this downward trend would continue, but indicated that a decision needed to be taken before winter, when respiratory virus cases usually increase.
For the unauthorized vaccines, it is clear that the UK government could not recommend them before their regulatory approval, but clinical results will still be eagerly awaited. However, the reasons for that will be different in each case: Novavax has shown excellent efficacy in its pivotal trial, but has been delayed by manufacturing problems; CureVac produced disappointing results in its Phase III study, but promising results in a booster study might save it from being abandoned; Valneva was this week informed by the UK government that its contract had been terminated, and there are rumors this was linked to poor results in the Cov-Boost trial.
The study will also contain results for AstraZeneca and Johnson & Johnson’s vaccines as boosters, which could be particularly relevant to developing countries, even if their use looks set to drop off in developed nations.
The central premise of the Cov-Boost trial was that heterologous vaccination often produces a stronger immunological boost than homologous vaccination, and so those who received an mRNA shot might have been recommended AstraZeneca as a booster. As this has not been recommended, it is possible that it did not perform as well as the mRNA vaccines as a booster shot, but only the full trial results from the Cov-Boost trial can clarify this.
However, Lim’s reference to the need for ‘simplicity’ could be key: having just two mRNA-based vaccines to administer (with fewer associated safety concerns) may well have swung the decision.
An early indication of the decision also came last month, when the UK ordered an extra 35 million doses of the Pfizer-BioNTech vaccine on top of another 60 million ordered earlier in the year, while no similar extra order was made with AstraZeneca.
Nevertheless, the JCVI's making its recommendations without the key data being publicly available has not gone unnoticed. No explanation for this situation was put forward by the JCVI, and Cov-Boost trial investigators did not respond to Scrip's request for an update on its likely publication date.
Penny Ward, independent pharmaceutical physician, visiting professor in Pharmaceutical Medicine at King’s College London, said the JCVI guidance looked to be a “natural follow-on” from the observed waning in vaccine effectiveness.
However, she noted: “Regrettably the data which underlies the JCVI’s preference for mRNA vaccine booster doses has not yet been made public, so the precise reason for this recommendation cannot be assessed.”
“These studies were publicly funded and the analysis has been completed in time to affect decision making and should be made available to prescribers, who will need access to these data to be able to answer questions from patients.”
The reason for the announcement being made without the data publication is unclear. If the JCVI was able to draw on the study to make its decision, this suggests the reason was not because of immature data, but rather because of political factors. This could relate to issues such as the Valneva contract termination, or simply the need for a swift decision to begin the booster program in combination with winter flu jabs.
Lim and Jonathan Van-Tam, England's deputy chief medical officer, said the decision did not mean that COVID-19 boosters would become an annual immunization. However they did indicate that older people should seek out both a COVID-19 booster and a flu jab, having them at the same time wherever possible this year, in order to maximize protection against respiratory illness.