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The results of the phase 3 clinical trials of the Pfizer/BioNTech COVID-19 vaccine candidate have been published in NEJM.
Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:
“We have already seen the headline results for this vaccine over the past few weeks. And like the results from other vaccine trials the interim analyses are based on relatively small numbers of COVID-19 cases in each vaccine vs. placebo arm.
“The Pfizer-BioNTech vaccine trial is of a much simpler design than that of the Oxford-AstraZeneca trials – with a single type of placebo (saline) and more consistent dosing and dosing schedules – with similar primary clinical end points: at least one COVID-19 compatible symptom with PCR-confirmed SARS-COV-2 infection.
“They report a 52% vaccine efficacy after a single dose:
“The study was not designed to assess the efficacy of a single-dose regimen. Nevertheless, in the interval between the first and second doses, the observed vaccine efficacy against Covid-19 was 52%, and in the first 7 days after dose 2, it was 91%, reaching full efficacy against disease with onset at least 7 days after dose 2.”
“And although not powered to examine individual high risk subgroups specifically, their results for these groups look promising:
“Although the study was not powered to definitively assess efficacy by subgroup, the point estimates of efficacy for subgroups based on age, sex, race, ethnicity, body-mass index, or the presence of an underlying condition associated with a high risk of Covid-19 complications are also high. For all analyzed subgroups in which more than 10 cases of Covid-19 occurred, the lower limit of the 95% confidence interval for efficacy was more than 30%.”
“But like other vaccine trials – more data is needed to fully assess the vaccine performance in these groups – including for younger children, pregnant women and the immunocompromised.
“The authors also raise an interesting point about the longer-term (2 year) planned safety followup, comparing vaccinated vs. placebo arms – in that it may not be ethical to keep the placebo arm unvaccinated for so long if/when the vaccine is approved, so this comparative safety followup period may eventually be much reduced:
“Although the study was designed to follow participants for safety and efficacy for 2 years after the second dose, given the high vaccine efficacy, ethical and practical barriers prevent following placebo recipients for 2 years without offering active immunization, once the vaccine is approved by regulators and recommended by public health authorities.”
“The authors do also mention that they are going to improve the vaccine formulation to ease the need for the ultra-low (-70C) storage and delivery requirements:
“The current cold storage requirement may be alleviated by ongoing stability studies and formulation optimization, which may also be described in subsequent reports.”
which will make it much easier to deliver, and is quite feasible – they could have done this before releasing the vaccine earlier – as other teams working on mRNA vaccines are doing.
“They finish by restating the breakthrough of mRNA vaccines being used in large-scale human populations against an infectious agent:
“The data presented in this report have significance beyond the performance of this vaccine candidate. The results demonstrate that Covid-19 can be prevented by immunization, provide proof of concept that RNA-based vaccines are a promising new approach for protecting humans against infectious diseases, and demonstrate the speed with which an RNA-based vaccine can be developed with a sufficient investment of resources.”
“But we still need to see how this mRNA vaccine performs over a much longer period over a much larger, non-trial population – before reaching a verdict on this.”
Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:
“The publication of the results of the phase 3 trial of the Pfizer/BioNTech COVID vaccine have now been published. This follows the publication of the results of the Oxford AstraZeneca vaccine by just a few days and it is very tempting to compare the two. As has been widely reported the Pfizer/BioNTech vaccine is an mRNA vaccine whilst the Oxford AstraZeneca is an adenoviral vector vaccine.
“The Pfizer/BioNTech included data on 43,448 participants compared to 8,895 in the Oxford AstraZeneca standard dose regimen and 2741 in the Oxford AstraZeneca low dose regimen.
“As far as I can tell both trials had similar primary outcome measures so they were measuring the same thing.
“The estimated vaccine efficacy for Pfizer from 7 days after the second injection was 95.0% (Confidence Intervals 90.3 to 97.6%). By contrast the efficacy for the Oxford standard dose regimen was 62·1% (41·0 to 75·7%) and for the low dose regiment was 90·0% (67·4 to 97·0%). Reflecting the smaller number of participants in the two Oxford dose trials, its efficacy estimates are much less precise and so more uncertain than the Pfizer study. The Pfizer study presented estimates of the effectiveness in older people and found efficacy >90% in >55, > 65 and >75 year olds, though confidence intervals were wider in the older age groups. The efficacy of the Oxford vaccine in people over 55 years could not be assessed and the low dose vaccine was not given to people over 55 so there is no data on that dose regimen. The Pfizer study reports good efficacy in Black and Hispanic participants. The Oxford study has not yet reported on efficacy in BAME populations. Neither study had sufficient numbers of cases of severe COVID or fatalities to make precise estimates of efficacy at preventing severe disease. Of ten cases of severe COVID in the Pfizer study 9 were in the placebo group and 1 in the vaccine group. In the Oxford study there was just 1 severe case and ten hospitalised cases and they were in the placebo group. The Pfizer study did not report studies of the impact of its vaccine on asymptomatic infection. The Oxford study reported that efficacy for “asymptomatic or symptoms unknown infection” based on weekly self-swabbing was 3·8% (−72·4 to 46·3%) following standard dose and 58·9% (95% CI 1·0 to 82·9) following low dose regimen.
“As to safety The Pfizer trial reported serious adverse reactions in 0.6% of vaccine recipients and 0.5% of placebo recipients. In the Oxford study serious adverse events were reported in 168 participants, 79 of whom were in the vaccine group (1.4%) and 89 were in the control group (1.5%), many of whom received a meningococcal vaccine. It would appear that the Pfizer vaccine study reported a lower risk of serious adverse events than the Oxford study but in both studies the probability of severe side effects was not that different between the vaccine and control arms. But many of the Oxford control subjects received a meningococcal vaccine which itself may cause serious adverse events so this needs to be interpreted carefully.
“So in conclusion the results do suggest that both vaccines are effective and safe. However, the Pfizer vaccine has rather greater reported efficacy than the Oxford standard dose vaccine and possibly fewer serious adverse reactions. The Pfizer study also has evidence showing high efficacy in older age groups and in Black and Hispanic but not yet Asian individuals. The Oxford study does not yet enable efficacy in these at risk groups to be determined. As yet there is no phase 3 data on the low dose Oxford vaccine in people over 55 years old, the main target group for immunization against COVID”.
‘Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine’ by Fernando Polack et al. was published in NEJM on Thursday 10 December.
DOI: 10.1056/NEJMoa2034577
All our previous output on this subject can be seen at this weblink:
www.sciencemediacentre.org/tag/covid-19
Declared interests
Dr Julian Tang: Dr Julian W Tang is a clinical virologist who supervises diagnostic virology testing and advises clinical teams and GPs on the management and infection control of viral infections – including advice on antiviral and vaccine safety and efficacy.
None others received.