With rising concern that Donald Trump would attempt to push out a vaccine ahead of the election, despite a lack of data on safety and efficacy, nine leading vaccine researchers and manufacturers signed a pledge earlier this month not to submit their vaccine candidates to the FDA until large-scale “Phase 3” trials have been completed. However, with Trump promising a vaccine “very soon” since the beginning of March, and the CDC shocking states by telling them to prepare for a vaccine by Nov. 1, restoring faith in the vaccine process called on many to demand that the manufacturers practice radical transparency by releasing their plans for testing.
On Thursday, two of the leading vaccine manufacturers—Moderna and Pfizer—did exactly that by releasing detailed plans for their Phase 3 testing. Moderna’s 135-page description covers how they plan to distribute vaccines among 30,000 volunteers, with results expected in November. Pfizer’s plan includes 44,000 volunteers and does not give an expected date for completion of Phase 3.
Both companies have triggers that could end the trial early, including triggers that might show the vaccine was ineffective. However, even if the trials ended in the next two months, the companies acknowledge that analysis of the data—an absolute necessity to properly assess safety, efficacy, and proper dosage—could take several months more.
All of this supports previous statements by National Institute of Allergy and Infectious Disease Director Dr. Anthony Fauci and CDC Director Robert Redfield, both of whom have said that vaccines are not likely to be available to the general public until sometime well into 2021.
Moderna’s candidate vaccine involves messenger RNA enclosed in a lipid shell. It’s a form of vaccine that has never been approved before in humans. A 2017 review of the company’s efforts suggested that Moderna had “run into troubling safety problems with its most ambitious therapy” and that in order to get its vaccine technology approved the “unicorn” biotech startup was “in need of a Hail Mary” to survive.
For Moderna, their COVID-19 vaccine is that Hail Mary. They really, really need this to work. That could lead to a company pushing too hard for success, and Moderna’s rapid release of early data from Phase 1 and 2 trials only amplified those concerns. However, the Phase 3 trial looks to be, if anything, conservative in its approach.
At this point, Moderna has already enrolled over 25,000 volunteers, 10,000 of whom have received their first dose of vaccine. The plan is to enroll 5,000 more, with half of volunteers eventually receiving an initial shot of vaccine followed by a booster, with a total dosage of 100 μg. That dosage is in the middle of the levels used in Phase 2 testing, where some patients who received a higher dose reported moderate reactions. The other half of volunteers will receive a placebo.
COVID-19 infection rates among patients receiving the vaccine vs. those receiving the placebo will be compared after 53 cases of COVID-19 have been diagnosed. This point represents a potential early stopping point at which the vaccine may be found to be particularly effective or ineffective. Moderna is shooting for a minimum of 74% efficacy to consider the vaccine a success. So, if the magic number of 53 cases is reached, and more than 74% of those are among the placebo group, that could be a point where the company declares “good enough.” Likewise, if the vaccine proves less than 74% effective at that point, the trial could be suspended or halted. As was recently seen with the AstraZeneca trial of the vaccine developed at Oxford, any safety issue that pops up could also suspend or halt the trial.
Pfizer, which has partnered with German tech firm BioNTech, has a similar plan overall. Their vaccine is also using a new technology based on messenger RNA, and while this is not a make-or-break moment for this large, established pharmaceutical company, there’s little doubt they want a share of the multibillion dollar pie for COVID-19, as well as the chance to fast track future mRNA vaccines using their technology, which involves a different delivery system than Moderna. Both of these companies aren’t just competing to deliver a vaccine for COVID-19: They’re hoping to open the door to a whole new approach to vaccines that could greatly extend the range of what we think of as a “vaccine.”
Pfizer plans to enroll 44,000 volunteers, also equally split between those receiving the vaccine and the placebo. And, like Moderna, they also have a number of cases that will trigger a first analysis. In Pfizer’s case, that number is 32. With a larger number of volunteers and a smaller number of cases required to trigger a possible halt, it can be argued that Pfizer is actually hurrying things along more aggressively than Moderna.
Moderna’s plan also includes a timeline that suggests that first analysis of Phase 3 results is not likely before November, and may not happen until some time in late December. Final analysis before distribution of vaccine is not expected before spring of 2021.
Pfizer does not provide a detailed timeline for its plan, but it’s safe to assume it cannot possibly meet Donald Trump’s claims that a vaccine would be available as soon as October, because Pfizer is not even halfway through enrolling people for their trial. Their overall timeline is likely to be similar to that of Moderna, putting a vaccine on the street (i.e. at your local clinic) around the second quarter of 2021.
Earlier this week, after Redfield once again testified to Congress that a vaccine was unlikely to be available this year and stated that a mask may be more effective than a vaccine, Trump hurried to contradict the CDC director, saying, “It’s just incorrect information.” Which is exactly the kind of statement that has half of American adults unwilling to take a COVID-19 vaccine under Trump.
Note: The vaccine trial that I’ve signed up with has now been confirmed to be a trial of the AstraZeneca/Oxford vaccine. This trial is still suspended in the U.S. pending investigation of a potentially serious reaction in one U.K. volunteer. AstraZeneca has stated that it cannot provide more public information about the incident due to international laws around privacy of medical data. Assuming the trial resumes, it’s my intention to go forward as a participant, and I will report on the experience within the limits of any agreements involved.