By Jenny Strasburg
LONDON -- AstraZeneca PLC and the University of Oxford added their vaccine candidate to a growing list of shots showing promising effectiveness against Covid-19 -- setting in motion disparate regulatory and distribution tracks that executives and researchers hope will result in the start of widespread vaccinations by the end of the year.
AstraZeneca and Oxford said their vaccine was as much as 90% effective in preventing the infection without serious side effects in large clinical trials, though they said the vaccine's efficacy varied widely based on dosage.
At the lower end, the vaccine's 62% efficacy trailed the trial results issued by rival drugmakers so far. The limited results at the top end of the range, however, came close to matching those of two other Western-developed vaccine candidates, one from Moderna Inc. and one from Pfizer Inc. and Germany's BioNtech SE. Each of those showed efficacy of more than 90% in early results disclosed recently.
These preliminary findings, all from so-called Phase 3 human trials, represent the first look at the effectiveness of experimental Covid-19 vaccines and open the way for the companies to seek regulatory authorization and gear up their distribution plans. That process is now under way for all three of the West's front-runner vaccine candidates, though at different speeds in different parts of the world.
"If there is anyone out there who still doubts that a Covid-19 vaccine can help us out of this pandemic, the announcement today...should surely dispel that doubt," said Prof. Eleanor Riley, an immunology and infectious-disease expert at Scotland's University of Edinburgh.
China and Russia have both deployed their own vaccines at home and overseas. Chinese authorities have inoculated nearly one million Chinese people with a vaccine from one state company, though it has yet to provide solid clinical evidence of its efficacy. Russia has said its own homegrown vaccine has an efficacy rate of above 90%.
Pfizer said last week it had submitted its vaccine to the U.S. Food and Drug Administration for approval for emergency use, a route that has expedited approval for several Covid-19 treatments. That puts Pfizer and partner BioNtech in the pole position for winning authorization in the U.S. first. The FDA hasn't specified a timeline for approval, but it could come within weeks, followed by the start of vaccinations shortly thereafter.
Moderna is right behind Pfizer and could make a submission as early as next month. It has said it could start rolling out its vaccine the same month.
AstraZeneca is further behind in the U.S. since the large-scale trials disclosed Monday were conducted in the U.K. and Brazil, not in the U.S. AstraZeneca's trials in the U.S. were temporarily halted after a British trial subject fell ill.
The company, which is based in Cambridge, U.K., said Monday it would seek permission to modify its U.S. trials, to provide for more testing of the dosage regimen that proved the most effective in its U.K. and Brazil trials. That could take several weeks, setting back possible FDA approval.
The AstraZeneca-Oxford vaccine has some advantages that experts say could make for a faster rollout outside the U.S., after regulatory approval, particularly in the developing world. The partners committed to selling it without profit during the pandemic and promised to distribute it across a much wider geographic footprint, including in large parts of the developing world. The shot is expected to cost $3 to $5 a dose globally during the pandemic, and AstraZeneca has committed to supplying some three billion doses by 2022.
The shot was created from a more traditional vaccine methodology compared with the gene-based technology used by Moderna and Pfizer. The Oxford-AstraZeneca shot doesn't need to be stored in subzero temperatures, making its rollout easier, researchers and logistics experts say.
"A particular strength of this vaccine is that it can be stored in a fridge," said Prof. Azra Ghani, chair in infectious disease epidemiology at Imperial College London. "This means that it can be distributed around the world using existing delivery mechanisms."
AstraZeneca said it would seek emergency-use authorization from the World Health Organization to distribute the vaccine in low-income countries and prepare regulatory submissions to authorities in countries that have early-approval programs.
Pending regulatory authorization, the shot could be available in limited volumes by year-end, with hundreds of millions more doses available in the first few months of next year, AstraZeneca executives said. The level of output depends on manufacturers across the world that are working with AstraZeneca to produce the vaccine.
The European Medicines Agency, which authorizes new medicines for sale in the European Union, said in early October that it had begun a rolling review of the Oxford vaccine to speed up a potential approval. A rolling review allows regulators to evaluate preliminary data such as those from lab experiments before final-stage clinical trials are completed.
Officials in the U.K., which is transitioning out of the EU, say they have the power to authorize use of a Covid-19 vaccine in the country before year-end, if they choose. The U.K. also has been reviewing Oxford and AstraZeneca data on a rolling basis since early November. Canada has also begun a rolling review of the vaccine.
Monday's results from AstraZeneca and Oxford left big questions about how the vaccine will ultimately stack up against the shots from Moderna and Pfizer. The higher efficacy result of 90% applied to a subset of trial participants -- somewhere above 3,000 out of about 23,000 -- that received half a dose of the vaccine followed by a full, standard dose. The remaining bulk of trial volunteers received two full doses and produced the lower efficacy result of 62%.
Prof. Sarah Gilbert, one of Oxford's lead scientists on the vaccine, said researchers are digging into why the half-dose regimen was shown to be more effective. She said it could be that the lower first dose better mimics the natural human immune system, coaxing the body to be ready for an eventual fight against the virus in a way that makes the second, standard dose more effective.
Two-dose vaccines often behave differently from single-dose vaccines, Oxford scientists said. With the latter, a stronger dose is usually closely matched with higher efficacy. With two doses, the first dose acts as a primer for the second dose.
In an interview last week about broader vaccine concerns, Jeremy Farrar, director of the Wellcome Trust, a U.K.-based global health foundation and backer of Oxford's vaccine research, said his biggest worry overall about access to vaccines is that the highest-quality shots will be narrowly available.
Of possible scenarios, Dr. Farrar said, "the one that worries me the most, I suppose, is this sense that there'll be poor vaccines for poor people, either in country or between countries."
He and others point out massive efforts to fund vaccine purchases for low- and middle-income countries. However, volume limits could still constrain global access.
The Wellcome Trust's head of vaccines, Dr. Charlie Weller, called the Oxford-AstraZeneca results "hugely encouraging." The preliminary efficacy results suggest the vaccine is "highly effective in protecting serious illness and it may reduce transmission," Dr. Weller said.
Some Wall Street analysts said the results would likely mean the Oxford-AstraZeneca vaccine finds global use, but possibly with adoption focused in poorer countries.
The vaccine's ease of storage "and very low price still likely assures significant global use, especially in less developed countries," Citigroup Inc. healthcare analyst Andrew Baum said in a research note that called the results "underwhelming."
The dosage that resulted in 90% efficacy wasn't convincing given its small sample size and the lack of a clear explanation by Oxford and AstraZeneca of the "biologic rationale" of pairing a half-dose with a full dose, Mr. Baum wrote in his note. Furthermore, he said the early results could hurt AstraZeneca's ability to finish recruiting participants for ongoing U.S. late-stage trials.
Some researchers said it will be important to compare the effectiveness and safety of the leading vaccine candidates. Oxford and AstraZeneca officials said such comparisons are difficult at this stage, but added that different shots are likely to be effective in different people -- a result that scientists expect to be a positive for fending off serious Covid-19 symptoms and halting the virus's spread.
Like with other Covid-19 vaccines in development, researchers don't yet know how long the positive effects of the shot last, which is key to understanding the required frequency of vaccination. It will also affect overall effectiveness in preventing the spread of the disease and helping jump-start stricken economies.
Write to Jenny Strasburg at firstname.lastname@example.org
(END) Dow Jones Newswires