There continues to be an unparalleled volume of news about COVID-19, but we are again this week focusing on one important story—Pfizer and BioNTech’s
announcement of preliminary data from their COVID-19 vaccine efficacy trial. The announcement that the independent data safety and monitoring board’s review of the data showed an efficacy of more than 90 percent was much-needed good news as the virus continues to ravage communities around the world. You can read TAG and AVAC’s statement on the announcement
here.
NIAID’s Anthony Fauci was optimistic about the finding as quoted by
Bloomberg: “Certainly it’s not going to be a pandemic for a lot longer, because I believe the vaccines are going to turn that around. Vaccines will help us. What we’ve got to do is just hang on and continue to double down on the public health measures…. Help is on the way, but it’s not here yet. To me, that’s more of an incentive of ‘Please don’t give up. Don’t despair. The end is in sight.’”
But what does this single data point shared in a press release mean and what are the next steps?
The Economist tweeted a picture of this week’s cover (a syringe lighted at the end of a tunnel) with this message: “The promise of the new COVID-19 vaccine is immense. But don’t underestimate the challenge of getting people vaccinated.” That is this week’s news in a nutshell, but read on for details and nuance.
Novel Platform
The vaccine, as Laurie Garrett writes in
Foreign Policy, “is unlike any vaccine ever used, for any disease. What is actually injected is messenger RNA (mRNA)—the genetic blueprint for protein production—triggering human cells to manufacture millions of copies of the spike protein that protrudes from the surface of SARS-CoV-2 viruses. As those spike proteins circulate in an immunized person’s body, they hopefully make antibodies and other immune system components to fight it off. Thus, the mRNA triggers production of decoys that train the immune system to ‘see’ the virus if it arrives in the body and destroy it.”
Regulatory Decisions
As
STAT reports, “In keeping with guidance from the Food and Drug Administration, the companies will not file for an emergency use authorization to distribute the vaccine until they reach another milestone: when half of the patients in their study have been observed for any safety issues for at least two months following their second dose. Pfizer expects to cross that threshold in the third week of November.”
STAT also notes, “Although it is a bright spot in the battle against the pandemic and a triumph for Pfizer and BioNTech, a German company, key information about the vaccine is not yet available. There is no information yet on whether the vaccine prevents severe cases, the type that can cause hospitalization and death. Nor is there any information yet on whether it prevents people from carrying the virus that causes COVID-19, SARS-CoV-2, without symptoms.”
The Economist reports, “If emergency authorisation is granted it is likely the agencies [in the US and Europe] will restrict the use of these vaccines, initially, to those at highest risk of death or serious disease. If after seeing the full data the regulators still have worries they may continue to limit the vaccines’ use. Whatever they decide they are very likely to insist on years of follow up.”
When Will We See More Data?
In
Science Jon Cohen writes that the answer to this question is not clear. “The companies say they won’t have more data, such as the breakdown of cases by groups, until the study ends. FDA has stated it will convene its vaccine advisory committee, an external group that has no conflicts of interest, if any company submits a request for a COVID-19 vaccine EUA, and those meetings are public. Advisory committee meetings typically include presentations from company scientists that involve detailed descriptions of their data, which are then discussed. The company may also post data to a preprint server or submit a paper to a peer-reviewed journal at any time.”
Outstanding Questions
As the world awaits additional data from the trial,
Nature identifies several key questions that still need to be answered, including “details about the nature of the infections the vaccine can protect against—whether they are mostly mild cases of COVID-19 or also include significant numbers of moderate and severe cases… whether the vaccine can prevent people who show no or only very mild symptoms of COVID-19 from spreading the coronavirus…. how well the vaccine works in different groups of trial participants [especially the elderly]… and how long the vaccine’s effectiveness will last.”
Access
NPR reports “The US, UK, EU, Canada and Japan have already claimed, through advanced purchase agreement, about 1.1 billion doses, or more than 80 percent of the supply” of an expected 1.3 billion doses Pfizer says it can manufacture in the first year. That leaves very few doses for the rest of the world.
The Economist reports “The British and American governments have said that vaccinations could start in December. The countries of the EU have also been told it will be distributed quickly.”
The Star (Kenya) reports, “Kenyans are likely to wait until late next year to receive the Pfizer-BioNTech vaccine.” Pfizer has expressed interest in the COVAX facility, which is how Kenya would have access to the vaccine, “however, the company must first fulfill pre-purchase orders signed with the United States, European Union and a few other rich countries running into millions of doses, to be supplied this year.”
Vanguard News (Nigeria) reports “President Muhammadu Buhari has welcomed the arrival of the first effective coronavirus vaccine…but warned that the world must unite in facilitating the equitable access and distribution of these vaccines to protect people in all countries.
Daily Maverick (SA) reports “Thus far, South Africa has not secured doses of candidate vaccines from Pfizer or any other manufacturer. The country also missed the first deadline to commit to COVAX—an initiative co-lead by the World Health Organisation that aims to ensure developing countries get access to COVID-19 vaccines. Spokesman for the Department of Health, Popo Maja, confirmed South Africa had not concluded any vaccine deal, but added negotiations with manufacturers and COVAX were underway.”
For more on access check out AVAC’s
Advocates Guide to COVID-19 Vaccine Access.
Distribution
Vaccine efficacy is only the first hurdle. Once a vaccine has a government approval, getting to the people who most need it is complicated.
The
New York Times reports, “If Pfizer receives authorization for its vaccine from the Food and Drug Administration in the coming weeks, as expected, the company in theory could vaccinate millions of Americans by the end of the year, taking advantage of months of planning and decades of experience…. The effort will hinge on collaboration among a network of companies, federal and state agencies, and on-the-ground health workers in the midst of a pandemic that is spreading faster than ever through the United States…. If an analysis planned for next week confirms the vaccine’s safety, the company is likely to ask the FDA this month for emergency authorization to distribute its vaccine. In that case, limited doses will most likely be shipped to large hospitals and pharmacies to be provided to health care workers and other vulnerable groups.”
Garrett writes in
Foreign Policy that “mRNA is very unstable. To prevent breakdown, it must be stored right up until the time of injection at a temperature of
at least -103 degrees Fahrenheit—well below anything a standard freezer unit can manage. Few health departments, hospitals, or doctors’ offices currently have stockpiles of dry ice or ultrafreezers that can manage to consistently hold temperatures that low, and none have piles of portable units that can do the job. Dry ice in coolers could do the job, but the world is facing a
shortage in pure carbon dioxide, which becomes dry ice when frozen.”
The Economist notes, “If vaccines are approved for widespread use, the world will face what some have called the largest supply-chain challenge in history. There is normally little spare vaccine-manufacturing capacity to repurpose. And production is not the only limiting factor. Analysts at UBS, a bank, warn that “fill and finish”, where the vaccine is put into vials and packaged, could be one of the most significant bottlenecks.
Reuters quotes “public health expert Evelyn Castle, executive director of the Nigeria-based non-profit organisation eHealth Africa, which in 2016 helped distribute an Ebola vaccine in Sierra Leone at similar temperatures” to what the Pfizer vaccine requires: “’We would need all new infrastructure… (In Sierra Leone), we had to do full renovations of some of the facilities we worked in.’ In Nigeria, many rural health centres have solar-powered fridges, but Castle said they lack the power to hit -70°C. Generators would be needed, along with someone to ensure they were serviced, fuelled, and monitored constantly so they didn’t drop below the temperature threshold, she said….’If we have a limited number of vaccines, who are we going to target? Are we really just going to be giving this to the rich people living in cities?’”
Unblinding and Access for Placebo Recipients
In many clinical trials it’s common for placebo recipients to get an effective vaccine or drug before approvals are granted from regulatory officials. But for COVID vaccines that decision is complicated. As
STAT reports “the timing of the decision is complicated in the case of COVID-19, with potential consequences for clinical trials. The FDA has indicated it wants vaccine manufacturers to keep their trials blinded for as long as possible; early unblinding could mean that safety and efficacy results would be less reliable after that point. That’s because volunteers who received the vaccine could no longer be compared to an untreated placebo group…. In an interview earlier this week, William Gruber, a senior vice president of vaccine clinical research and development at Pfizer, said that the company planned to switch people from placebo to a vaccine if there was a regulatory approval and, perhaps, clearance from an expert panel organized by the Centers for Disease Control and Prevention.”
The Inevitable Politics
The Atlantic reports “If authorized, the initial rollout of this vaccine will likely begin in the fractious period before the inauguration, under a lame-duck president who claims that the election he lost was stolen. There will be a path to ending the pandemic, but it will be fraught. Joe Biden will have to restore trust in a vaccine that his predecessor has fervently politicized, and Americans will have to be willing to take the vaccine regardless of whom they voted for—if they voted at all. If not, the coronavirus will simply rage on…. Politicians won’t be the best messengers to encourage people to get vaccinated, by very dint of the fact they are polarizing figures. Biden will have to turn to other groups to boost confidence in a vaccine. Health-care workers will play a crucial role—both as the likely first recipients of a COVID-19 vaccine under CDC recommendations and as trusted sources of information in their communities.”
The Guardian quotes BioNTech’s chief executive, Prof Uğur Şahin in response to accusations from the US President that the results had been delayed until after the US election: “Pharmaceutical research should never be politicised. It’s a question of integrity. Withholding information would have been unethical. What’s important for us is that we are developing a vaccine and we don’t play politics.”
Moderna Data Coming Soon
CNBC reports Moderna expects to soon release data from its study, which is studying a similar vaccine candidiate. “Moderna said it expects at least 53 people in the study contracted the virus, the minimum number required for an independent data safety monitoring board to review and measure how well the vaccine works in those who received it. “It’s unknown how many infections will be evaluated in Moderna’s interim analysis. And while Moderna may announce the vaccine’s overall effectiveness, the public will likely still have to wait for other key details, like how effective the vaccine is in the elderly or people with preexisting conditions, said Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia.”
