The U.S. found itself this month both in the most dangerous stage of the Covid-19 pandemic to date, and in the most hopeful stage.
Just as the daily case counts of new coronavirus infections surged toward 200,000, the developers of two different vaccines said their shots were around 95% effective at preventing development of full-blown Covid-19 in patients. One of those vaccine makers even sought on Friday emergency approval for its vaccine's use in the U.S.
But, so far, publicly available information on the most recent data behind the vaccines' late-stage trials has been sparse. In fact, virtually all anyone knows about the vaccine candidates yet is from the companies making them -- Pfizer (PFE) - Get Report and BioNTech (BNTX) - Get Report and Moderna (MRNA) - Get Report. So, while the world is left with a big light at the end of a dark and deadly tunnel, it’s not yet sure how far away that light really is.
“I'm personally optimistic, but we have yet to see vaccine experts go through the data from Phase 3 trials,” said virologist Ian M. Mackay, an associate professor at the School of Medicine at the University of Queensland in Australia, in an email to TheStreet late last week. “We all have to wait for a wide range of expert scrutiny to understand how much of the picture has been released in competing media proclamations thus far. We all want these vaccines to work and we all want the pandemic to be over, but on vaccines, we need those safety and effectiveness data to be intensely scrutinized, because wishful thinking isn't enough.”
Over this past week, TheStreet asked Mackay and several other experts – in virology, epidemiology, microbiology, biotechnology and infectious diseases – about various aspects of the vaccine news released this month. Most of them have been closely following the coronavirus pandemic since its start. All were similarly optimistic about the progress shown by Pfizer and Moderna, but some were more guarded on whether the numbers and proclamations in the press releases will meet up to the great expectations. None saw immediate concerns for the safety of the shots, which appear so far to be well tolerated.
Pfizer and BioNTech’s candidate, called “BNT162b2,” showed an efficacy rate of 95%, according to a press release. In their study, which includes around 44,000 total participants from around the world – most of whom were vaccinated – 170 people developed Covid-19. Of those, 162 were in the placebo group and eight were in the vaccine group. Ten of the cases were severe – and one of those patients who developed severe Covid-19 actually had the vaccine.
Pfizer and BioNTech promise that if they get their vaccine OK’d by federal regulators soon, tens of millions of doses could distributed to Americans by Christmastime -- or earlier. The FDA would not comment directly on the application to TheStreet.
Moderna said just last week that the Phase 3 study of its candidate, called “mRNA-1273,” has shown similar results, with an efficacy of 94.5%. Of the 30,000 adult participants, some of whom got the placebo and many of whom got the two-dose vaccine, 95 people tested positive for Covid-19. The vast majority of them, 90, got the placebo. The rest, five, were in the group who got two jabs of mRNA-1273.
Of the 11 people who developed “severe” cases of Covid, all were in the placebo group. No significant safety concerns were reported among the vaccinated.
“I think science by press release is tricky,” said Dr. David N. Fisman, a professor of epidemiology at the University of Toronto, in an email to TheStreet. “But these trial results are consistent with what one would have expected based on very promising Phase 2 data earlier in the summer. So I believe it.”
But at the same time, there are lingering questions. How safe will this new technology prove over a longer time, after given to millions or billions of people? How good will the vaccines prove at preventing the vaccinated – who might still develop very mild disease – from passing the virus on to the unvaccinated? How long will protection last? The world is dealing with an elusive virus it’s studied for less than a year, and now potentially vaccines that have been even less studied.
New Technology Is on 'Trial'
If the vaccines work as well as we’re told they do, they could be a big game-changer in the pandemic, and in medicine in general. Both vaccine candidates under study rely on similar “messenger RNA” technology, that would get further validation if the vaccines get approved for use. Moderna explains the complicated science behind mRNA medicines as sets of instructions that “direct cells in the body to make proteins to prevent or fight disease.”
Studied for use in other vaccines such as for the Zika virus and for types of cancer, mRNA technology shows great potential for vaccine development, according to a 2018 article in the journal Nature Reviews Drug Discovery, which said it appears a “promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration.”
Indeed, the results of the clinical trials so far, “vindicate proponents of mRNA-based vaccines,” said Richard H. Ebright, the laboratory director at the Waksman Institute of Microbiology and a professor of chemistry and chemical biology at Rutgers University, in an email to TheStreet, adding that the trial results should “set to rest doubts that many, including me, had about prospects this new vaccine technology would be successful.”
The new technology could be widely applicable to creating other medicines, said Dr. Otto O. Yang, a veteran infectious disease expert and medical doctor at the David Geffen School of Medicine at UCLA.
Big Promises, Potential Risks?
On the other hand, there’s the rare possibility that the technology could bring unexpected risks.
“That's certainly a concern, which is why the subjects in the trials will be followed for a long time,” said Dr. Henry I. Miller, who for many years worked at the Food and Drug Administration and who was the founding director of the agency's Office of Biotechnology. Eventually, he said, over several more months, concern about new side effects emerging should begin to diminish – and he did not say he was concerned specifically about the vaccines.
But there have been problems with past vaccines, even traditional ones. A swine flu vaccine in the 1970s led to hundreds of cases Guillain-Barre, a potentially deadly syndrome. A vaccine attempt for respiratory syncytial virus in 1966 killed two children and ended up making others after infection than had they never had gotten the shot. In 2009, hundreds of people also developed with Guillain-Barre after taking an H1N1 vaccine.
“That's why post-marketing surveillance is so important,” said Fisman. “If I were these companies and/or the Wold Health Organization, I'd be working really hard on innovation in that vaccine safety surveillance space. I think it's possible that we will see rare and unexpected adverse effects with vaccines used on this scale.”
Ebright, however, said he sees nothing in mRNA vaccine technology that suggests the possibility of new safety risks. Especially, he said, when compared with the risk profile of getting Covid-19 naturally.
What Kind of Vaccine Effectiveness?
But there are other questions about the data currently available.
What the press releases fail to reveal at this point, said Fisman, is whether the vaccines work against all infection or just “clinical” disease. If it’s effective against infection, he said, “we'll get more indirect protection out of these vaccines.”
A recent post in Brief 19, a digest of coronavirus news, made a similar point, saying that “if a vaccinated person can still be infected, they might very well be able to pass along the disease to others who in turn may develop life-threatening covid-19, even if they themselves are at far lower risk of developing symptoms, let alone a bad or life-threatening case.” The post, was written by Brief 19 editor, Dr. Jeremy Samuel Faust, an emergency physician at Brigham and Women’s Hospital in Boston, following Pfizer’s initial Nov. 9 press release about its vaccine candidate.
But Yang, at David Geffen School of Medicine at UCLA, told TheStreet he’s not particularly worried about these vaccines or others failing to prevent spread of the disease between the vaccinated and non-vaccinated. "It’s a theoretical concern," he told TheStreet earlier, "but not something that I would be that worried about.”
A Numbers Game
Assuming the vaccines work as well as believed and they get emergency approvals, when will enough of them be distributed to quash the pandemic?
Despite hopes of a quick end to the outbreak, it appears that won’t come from either of these shots alone, at least not very soon. Pfizer and BioNTech say they expect to produce as many as 50 million doses in 2020 and up to 1.3 billion by a year from now. But those big numbers must be divided by two – the number of shots each person must get to fend off Covid-19. And they must be compared with the world’s population of around 7.7 billion.
“It's a small number, compared to the totality of the population,” acknowledged Pfizer CEO Albert Bourla in an interview on PBS’ “News Hour” program earlier in the month. "To put things into perspective, 50 million doses means 25 million people."
Moderna says by the end of 2020, it expects to have around 20 million doses of mRNA-1273 “ready to ship in the U.S.” It says it’s on track to manufacture 500 million to a billion doses globally by 2021. Again, two doses are needed for each patient.
And there’s one group that might not get vaccinated any time soon: Kids.
This group has so far largely been left out of clinical trial testing for vaccines, says the American Academy of Pediatrics. Pfizer in September, did expand enrollment of its Phase 3 trial to allow for enrollment of teens as young as 16 and soon after got FDA permission to enroll kids as young as 12. Still, those groups and younger will take time to study for the vaccines’ safety and effectiveness.
“We know that children can be infected with Covid-19 and can transmit it to others. To reduce the spread of this virus and control the pandemic as well as for their own safety, it’s crucial that children be included in the national vaccination program, and that vaccines are made available to children as soon as possible,” said Dr. Yvonne Maldonado, chair of the American Academy of Pediatrics committee on infectious diseases, in a press statement last week.
More than a million kids have been infected so far by the novel coronavirus, according to the academy. A small number have died or become severely sickened.
“Young children missing out to this point shouldn't be a hindrance to the main goal of the first generation of vaccines; to prevent disease and death and to protect our most vulnerable groups,” said Mackay. That said, the virologist does believe it would have been ideal for “everyone” to be part of the trials, including pregnant women. Mackay’s virology work includes researching viruses that infect the respiratory tracts of children, such as influenza viruses, coronaviruses and the picornaviruses.
Also, because the infection rate is likely going to be on the way down in reaction to the current surge, once these vaccines arrive, they could help make a big “dent” in the pandemic, said Fisman, despite their limited availability.
But there may be yet another uphill battle for how well these – or any vaccines – will help end the outbreak in the U.S.: A large portion of Americans don’t like the idea of getting a relatively safe substance they know little about injected into their arm. It’s more frightening, perhaps, than their increasing likelihood of breathing in invisible droplets containing a coronavirus that is known to kill, put people in the hospital for weeks and potentially leave them with lasting heart or neurological problems.
Around two in five Americans, in fact, say they would not get a Covid-19 vaccine once one is available, according to a recent Gallup Poll.
One thing the data released from the two vaccine projects make clear, however, is that getting the shots appears far safer than getting the virus.
“We all need to keep in mind they are aiming to prevent serious disease and death, and we don't yet know if they prevent transmission, ‘long Covid’ or things we don’t yet know are associated with SAR-CoV-2 infection,” said Mackay.
But we do know that getting the disease naturally will put patients at great risk for those, and possibly worse, outcomes.
“From all that we know right now -- and it isn't the full picture -- the leading candidates appear safe,” said Mackay. "There's no clear reason not to get vaccinated.”
The writer of this story can be reached here.