First Phase 3 COVID-19 vaccine trial data is promising, but hurdles remain
Pharmaceutical companies Pfizer and BioTech have announced the first data from their Phase 3 COVID-19 vaccine trial, claiming the experimental mRNA candidate is more than 90 percent effective in preventing symptomatic disease. Experts point out these interim results are encouraging, but it is early days and most of the trial data is still unreleased.
Of the ten COVID-19 vaccines currently in final phase trials, this Pfizer/BioNTech candidate is the first to report any interim Phase 3 findings. Dubbed BNT162b2, the COVID-19 vaccine is one of several being developed using a still experimental mRNA technology.
Despite promising signals over the past few years, no mRNA vaccine has progressed to clinical deployment stages. Trudie Lang, from the University of Oxford, explains how mRNA vaccines are different from more traditional kinds of vaccines.
“Most vaccines administer part of a virus (or inactivated whole virus) and this triggers an immune response which is then able to react to subsequent infections with the actual virus,” says Lang. “This potential COVID-19 vaccine uses mRNA technology, developed from use in cancer therapies. This vaccine instructs human cells to generate COVID-19 viral protein. This viral protein then causes an immune response that should enable a recipient of the vaccine to respond to a real COVID infection.”
The Phase 3 trial for BNT162b2 began enrolling subjects back in late July following successful safety trials. There are currently over 40,000 participants in the trial across six countries.
BNT162b2 is a two-dose vaccine, with the second dose required three weeks after the first. Protection is estimated seven days after the second dose, meaning the entire vaccination protocol will take 28 days.
Phase 3 vaccine trials work by blindly allocating participants to either active or placebo groups. Instead of running for a set period of time, data is analyzed once a certain volume of participants report infection. In this specific instance, after discussions with the FDA, the threshold for an interim analysis was raised from 32 positive COVID-19 cases to 62. The new data revealed by Pfizer ultimately encompasses 94 cases.
According to a press release from Pfizer, this interim analysis of the data suggests the vaccine has an efficacy rate of 90 percent. What this implies is that less than 10 of those 94 confirmed COVID-19 cases were in the active vaccine group.
Jeremy Farrar, an infectious disease expert and director of research charity Wellcome Trust, is optimistic about this new data. He suggests while there are many unresolved questions this is a promising early sign that COVID-19 vaccines should be effective.
“These interim results offer some very positive news in what has been an immensely difficult year,” says Farrar. “It is important that we look closely at the data, and there are critical questions that remain to be answered. This vaccine could be more effective than we ever hoped for from the first generation of Covid-19 vaccines.”
Perhaps the most critical unanswered question floating around this announcement is the lack of any detail regarding whether the vaccine protects against coronavirus infection, or merely reduces the severity of the disease. The threshold for a COVID-19 case in the Pfizer trial is participants suffering from at least one prominent symptom leading to a confirmed positive test.
However, what is not clear in the currently released data is the severity of the disease in both active and placebo groups, and whether asymptomatic cases are being tracked. The distinction between whether a vaccine protects from infection or merely reduces the severity of disease is important as it will fundamentally influence the course of the pandemic over the next one to two years.
“If there is also protection against infection (and thereby a reduction in potential for transmission of infection from an asymptomatic, infected person to others) then we might in future be able to reduce the other mitigating measures,” explains Penny Ward, from King’s College London. “However if the protection offered is primarily a reduction in risk of disease, but not against infection, then mitigating measures would need to remain in place until sufficient numbers of individuals have been vaccinated to protect those at most risk of needing hospital care or of dying from disease from becoming very unwell by catching the infection from a vaccinated, asymptomatically infected person.”
Another critical issue looming on the horizon is one of manufacturing and distribution. This particular vaccine requires extremely cold storage to prevent degradation. Ultra-cold chain transportation requires maintaining temperatures between -70 and -80 degrees C (-94 and -112 Fahrenheit). This will present significant logistical challenges in many parts of the world.
Pfizer suggests up to 1.3 billion doses of the vaccine will be available at some point in 2021. With vaccination requiring two doses this means it is unlikely more than 600 million people will be initially protected.
Despite these unanswered questions and looming challenges, most experts agree this interim data is extremely positive. Speaking to STATNews, America’s top infectious disease expert Anthony Fauci said these early findings suggest several other vaccine candidates in development will also be effective.
“There was always a discussion: Is the spike protein the right target? Well, now we know it’s the right target,” says Fauci. “So, it’s not only immediate good news, it really is optimistic about what’s going to roll out in the next several months with the other vaccines.”
Pfizer claims it will apply for Emergency Use Authorization through the FDA by the end of November. If granted by the FDA this means some populations may begin receiving the vaccine relatively soon.
The European Medicines Agency, the body evaluating new medicine approvals in the European Union, says the agency has not yet received any clinical trial data from Pfizer and does not expect any EU vaccine approval before early 2021.