Pharmaceutical company Pfizer and biotechnology company BioNTech have announced the first interim efficacy data from a large-scale trial evaluating BNT162b2, a vaccine candidate developed against SARS-CoV-2. Their press release indicates a vaccine efficacy rate of ~90% seven days after a second dose of the vaccine is administered, however the data is yet to be published.
In a press release, Dr Albert Bourla, Pfizer chairman and CEO said, "Today is a great day for science and humanity. The first set of results from our Phase 3 COVID-19 vaccine trial provides the initial evidence of our vaccine’s ability to prevent COVID-19."
Where has the data come from?
The Phase III clinical trial – which is open to recruitment – commenced on July 27 and has thus far enrolled 43,538 participants. From this sample, ~42% of global recruits and ~30% of U.S-based recruits have racially and ethnically diverse backgrounds. The study protocol dictates that participants receive either BTN162b2 in two doses that are three weeks apart, or a placebo solution. The trial is observer-blind, meaning the participants and their doctors are not informed as to whether they have received the vaccine or not.
What is an interim analysis?
An interim analysis involves reporting on data that is available in a clinical trial or scientific study before the full data collection is complete. Such studies, particularly when large in size, require substantial amounts of resources and funding. An interim analysis helps to provide insight as to whether the study is worth this investment, in a manner that is free from conflict of interest.
The interim analysis has been conducted by an external, independent Data Monitoring Committee (DMC) at a time-point in the trial when 94 participants have now received a positive COVID-19 diagnosis. Originally, the interim analysis was to be conducted when 32 cases were declared, however this figure was raised after discussions with the U.S Food and Drug Administration (FDA).
The DMC has analyzed whether the confirmed cases had been vaccinated with BNT162b2 or received a placebo and has concluded that the data suggests a vaccine efficacy rate of ~90% seven days after the second dose of the vaccine. "This means that protection is achieved 28 days after the initiation of the vaccination, which consists of a 2-dose schedule. As the study continues, the final vaccine efficacy percentage may vary," the press release states.
Pfizer and BioNTech intend to submit the data from the full Phase III trial for scientific peer-review.
Reasons to rejoice, or be cautiously optimistic?
The announcement from Pfzier and BioNTech will undoubtedly provide a much sought-after dose of optimism for society, particularly at a time when many countries across the globe are facing further lockdown restrictions and witnessing increasing COVID-19 case numbers.
However, it is important to acknowledge that the interim data is just that – interim; it is not the final outcome of the trial. Professor Azra Ghani, chair in infectious disease epidemiology at Imperial College London is advising the World Health Organization (WHO) and WHO-Europe on vaccine modelling to support allocation. Commenting on the announcement she said, "It is important to bear in mind that these are early results based on a relatively small number of cases. In addition, the efficacy estimate is based on seven days of follow-up of participants following the second dose; further data in the coming weeks and months will provide a better picture of longer-term vaccine efficacy.”
Neither Pfizer nor BioNTech have shared data pertaining to the age of the trial cohort, which Eleanor Riley, professor of immunology and infectious disease at the University of Edinburgh, suggests is pertinent: "The two companies are at pains to point out that the trial participants are ethnically diverse, which is good, but say nothing about the age of people in the trial. If a vaccine is to reduce severe disease and death, and thus enable the population at large to return to their normal day-to-day lives, it will need to be effective in older and elderly members of our society." She then added, "But, I think we have reason to be cautiously optimistic.”
A new era in vaccinology?
A particularly interesting aspect of the trial is BNT162b2's design, as it is an mRNA-based vaccine. Should it be approved as a preventative for COVID-19, it would be the first of its kind to be authorized for human use.
What is an mRNA-based vaccine?
Whilst most traditional approved vaccines are created from inactivated doses of a pathogen, or proteins that the pathogen produces, mRNA vaccines are a little different. They contain mRNA which encodes a specific antigen of the pathogen. When the mRNA enters the cell, it is used as a template to build the antigen. Once built, the antigen is presented to the body's immune system, which then prepares to fight the infectious disease.
A Nature review article outlines several benefits to the use of mRNA-based vaccines over traditional or DNA-based approaches, which include:
- Safety: as mRNA is non-infectious, there isn't any risk of mutagenesis.
- mRNA is degraded via cellular processes: therefore, its half-life can be controlled through modification and the use of specific, carefully selected delivery methods.1
The novelty surrounding RNA-based vaccines means the scientific community will no doubt place a close watch on BNT162b2's long-term performance, as Brendan Wren, professor of microbial pathogenesis at the London School of Hygiene and Tropical Medicine, explained: “A 90% efficacy for a Phase III trial is excellent for a new vaccine that could make a huge difference, but more confirmatory safety and efficacy studies are required. The RNA-based vaccine requires two doses and its true efficacy over a longer period of time remains to be evaluated. These are encouraging results and it is a case of so far so good.”
Should BNT162b2 ultimately prove safe and efficacious upon completion of the Phase III trial, it may still bode well for other vaccines that are in development – irrespective of design. Lawrence Young, professor of molecular oncology at Warwick Medical School, explained, "Almost all of the other vaccines using different technology platforms are focusing on the same virus spike protein. So it is likely that some of these other vaccines will also be able to prevent COVID-19," he said.
What is next?
The press release shared by Pfizer and BioNTech states that the companies are continuing to gather safety data, and estimate that a median of two months’ safety data following the second dose of the vaccine candidate will be available by the third week of November. This is the amount of safety data that is required by the FDA as warranting potential Emergency Use Authorization. Recruits in the trial will be monitored for long-term protection and safety for two years after their second dose of the vaccine or the placebo. In addition, Pfizer and BioNTech are also in the process of generating the required manufacturing data to submit to the FDA that illustrates the safety and quality of the vaccine product.
Whilst there is certainly a long road ahead when it comes to COVID-19 vaccination, members of the scientific community are sharing their initial delight. Professor Peter Horby from the University Oxford stated, "This news made me smile from ear to ear. It is a relief to see such positive results on this vaccine and bodes well for COVID-19 vaccines in general. Of course we need to see more detail and await the final results, and there is a long, long way to go before vaccines will start to make a real difference, but this feels to me like a watershed moment.”
In the press release, Pfizer and BioNTech share that they expect to produce up to 50 million doses in 2020, and 1.3 billion doses of BNT162b2 in 2021.
1. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines — a new era in vaccinology. Nature Reviews Drug Discovery. 2018;17(4):261-279. doi:10.1038/nrd.2017.243