Some 420 words into Pfizer Inc.’s press release announcing that a first peek at early data suggests its COVID-19 vaccine is more than 90 per cent effective, signalling a “great day for science and humanity,” came this cautionary note: “As the study continues, the final vaccine efficacy percentage may vary.”
The press statement, which sent hopes and global stock markets surging, was based on 94 confirmed cases of COVID-19 in a trial that has enrolled nearly 44,000 people, nearly 39,000 of whom have received both doses of the experimental vaccine known as BNT162b2.
Few other details were released. The early data have not been peer-reviewed or published. The vaccine seems safe, with no serious concerns observed, however safety information is still being accumulated. And while a 90 per cent efficacy, if it holds, would be “unbelievable,” scientists say, this was the first interim analysis, and not the final word.
With confirmed cases rising, nerves fraying and more than one million related deaths globally, the stakes are “beyond imagination,” Albert Bourla, chairman and chief executive officer of Pfizer told The Washington Post. The vast majority of Canadians remain susceptible to COVID-19 and, after seven months of this, there is so much anticipation for a vaccine that any good news is understandably celebrated.
“We see the light at the end of the tunnel,” Prime Minister Justin Trudeau said Monday at a briefing with reporters.
But experts caution that it’s too early to call this a vaccine win. It’s not known whether the vaccine prevented serious infections, or mainly mild ones, and it’s too early to know how long any immunity might last.
“It’s well known in clinical trials that sometimes when you have really, really positive effects in the interim analysis, those positive effects get smaller as you complete the trial,” said McGill University professor of biomedical ethics Jonathan Kimmelman. The phenomenon is known as regression toward the mean.
He and others don’t want to understate the significance of Pfizer’s update. A vaccine that provides more than 90 per cent protection against COVID-19 “would be absolutely amazing and would definitely go a huge way to leading us out of the pandemic,” said Toronto infectious diseases specialist Dr. Andrew Morris.
“I just want to see the evidence.”
Canada has bought the rights to 20 million doses of Pfizer’s vaccine. Ottawa, hedging its bets, has also signed pre-order agreements with Quebec-based Medicago, Moderna and other companies for up to 358 million doses of different vaccine candidates. A federal advisory committee has recommended those over 70 be first in line for vaccines, followed by healthcare professionals and then essential workers.
Monday’s statement by Pfizer and German partner BioNTech was based on an early analysis of its Phase 3 trial, the final stage of human testing. Volunteers are given either the experimental vaccine, which is administered in two doses, 21 days apart, or a placebo. Volunteers and researchers are “blinded,” meaning neither knows who gets what.
After 94 infections were confirmed among volunteers, an external, independent data and safety monitoring board found that “the case split between vaccinated individuals and those who received the placebo indicates a vaccine efficacy rate above 90 per cent, at 7 days after the second dose,” the companies said.
“Today is a great day for science and humanity,” Bourla said in a statement.
The reported 90 per cent efficacy rate, which surprised many experts, is above the 50 per cent minimum target the U.S. Food and Drug Administration has said it would require to grant emergency use authorization for any COVID-19 vaccine.
The trial will continue until there are 164 confirmed cases of COVID-19, and a median two months of safety data following the second and final dose — the amount of safety data the FDA wants. Volunteers will be monitored for “long-term protection and safety” for an additional two years.
The companies expect to seek U.S. emergency use authorization later this month and say they can produce up to 50 million vaccine doses globally in 2020, and up to 1.3 billion doses in 2021.
The Pfizer/BioNTech vaccine targets the spike protein that adorns the surface of the virus that causes COVID-19, raising hopes for other vaccines that use the same approach.
Still, the supply chain will be a challenge: an mRNA-based vaccine like Pfizer’s has to be shipped and stored at temperatures as low as minus 80 degrees Celsius, “as cold as the South Pole in the depths of winter,” as David Gelles of The New York Times noted.
Vaccines are also meant to do two things: protect the person who has been vaccinated from getting sick with disease, and protect the next person from being infected.
Still unknown: “Does (the Pfizer vaccine) attenuate the disease? Does it reduce spread to other people,” Morris, a professor of medicine at the University of Toronto said. “Those are equally important things.”
Also missing from Pfizer’s press release was any mention of whether the experimental vaccine prevents hospitalizations or deaths.
“You’d really need to see the full array of safety information to have a critical appraisal of the vaccine,” Kimmelman said.
A Royal Society of Canada policy briefing released last week on the furious pace of COVID-19 science and how it’s being communicated to the public cautions that many in Canada “already have concerns about any vaccine and hesitancy is on the rise.”
“If there is a reversal of fortunes for this vaccine, people in the public begin to have more doubts about what companies or various sponsors are reporting…. You really want to be confident that you have worked out all the kinks, that you have reliable findings before you go public,” Kimmelman said.
“Presumably, Pfizer is making this information public because they think it ought to inform some people’s decisions. Why not wait until you have carefully vetted the data, that you’ve completed the trial, before you issue these results?”
On Tuesday, Medicago reported that all 180 healthy volunteers in a Phase 1 trial developed a “robust” antibody response after two doses of its adjuvanted vaccine candidate. The federal government signed a $173-million contract to secure the rights to buy 76 million doses of Medicago’s vaccine, should it meet health and safety standards.
“I can understand the desire to give good news and to give hope, but we also need to be cautious, because these are life decisions that are being made around these products, and we want to make sure that they’re safe and ready to go,” Medicago president and CEO Dr. Bruce Clark said. The Pfizer report “encourages all of us that there is hope for a vaccine. That can’t be taken away from them at all. But it isn’t the answer yet, it’s not a vaccine yet. This is still a candidate vaccine in development, and we don’t know until we know.”