Drugmaker AstraZeneca announced today that early analysis of its late-stage clinical trials demonstrated that its coronavirus vaccine was 90% effective when given in one dosing regimen. However, the company said, it was only 62% effective in a different regimen. This is a complicated — albeit encouraging — result for a vaccine that the world will rely upon heavily.
While the virus has killed more than 1.3 million people worldwide so far, the vaccine was tested in British and Brazilian conditions. Its efficacy in other places of the world may vary.
AstraZeneca vs Pfizer vs Moderna
The data released today came from AstraZeneca’s Phase II and III clinical trials in Britain and its Phase III clinical trial in Brazil. The participants were randomly assigned to receive either the coronavirus vaccine or a meningitis vaccine as a control, followed by a booster shot about a month later.
AstraZeneca said it made the early analysis on the basis of 131 coronavirus cases among participants at least two weeks after they had received their second shot.
By early November, AstraZeneca had a total of 23,000 participants in mid- to late-stage trials in Britain, Brazil, South Africa and the US. The American results will not be made public until next year. That trial, which aims to enroll 30,000 participants, was slowed by the safety pause that lasted over a month.
Differences in methodology
In the trial in Britain, researchers swabbed subjects weekly to count the number of infections. The detection method was likely to have turned up more infections than the trials run by Moderna and Pfizer.
Moderna and Pfizer had previously tested people who developed symptoms and may have failed to find any asymptomatic cases.
The different approaches to counting infections could make it harder to compare how well the different vaccines work.
Oxford and AstraZeneca said that none of the vaccinated people who developed the disease required hospitalisation. Scientists had seen a reduction in asymptomatic infections. This suggested that the vaccine could reduce transmission.
The vaccine is proven 70% effective on an average across two dosing plans.
The AstraZeneca scientists gave study participants a half-dose of the vaccine. A month later, a full dose was administered. This produced better results.
The vaccine was less potent when the subjects were given a standard full dose upfront, followed a month later by another full dose.
If regulators finally authorise the more effective regimen across the globe, it could make the vaccine reach more people at a time of short vaccine supply.
The British-Swedish company, which has been developing the vaccine with the University of Oxford, became the third major vaccine developer in November to announce encouraging early results. Comparable to the product of AstraZeneca-Oxford, the vaccines of Pfizer and Moderna were about 95% effective in late-stage studies.
The results of the AstraZeneca vaccine could significantly strengthen the global effort to produce enough vaccine to create population immunity: The price of the shot, at $ 3 to $ 4 (less than Rs 300 in India), is a fraction of that of other vaccines in the competition. AstraZeneca has pledged to make it available at an affordable cost worldwide until at least July 2021 — in poorer countries in perpetuity.
The company says the vaccine can also be manufactured in mass quantities in a relatively easier manner. AstraZeneca expects to begin supplying the vaccine by the end of this year. It will make up to 3 billion doses next year.
The scientists said that they had not identified any “serious safety events related to the vaccine,” a reassuring sign. After AstraZeneca temporarily paused its trials in September to investigate potential safety issues after a participant in Britain developed a neurological illness — the vaccine had come under global scrutiny.
Oxford and AstraZeneca said they would submit the data to regulators in Britain, Europe and Brazil and seek emergency authorization to start distributing the vaccine there, and begin discussions about its data with regulators in the US.
Storage of AstraZeneca-Oxford vaccine easiest
The company said its vaccine could be stored for at least six months in a standard refrigerator. The vaccine does not demand intense chilly storage, unlike other leading coronavirus vaccines. This would ease its distribution while the AstaZenaca product is also cheaper and easier to produce.
Moderna’s vaccine can be kept for up to a month at the temperature of an ordinary refrigerator. Pfizer’s can be kept for up to five days in conventional refrigerators, or in special coolers for up to 15 days, but otherwise needs ultracold storage.
“Our goal is to make sure we can have a vaccine that was accessible everywhere,” Professor Pollard said. “I think we’ve managed to do that.”
Confusion and review
The Oxford scientists said they were still trying to understand why the vaccine was more effective at a smaller first dose. The first dose is supposed to trigger the immune system while the second is supposed to boost its response. “While it seemed counterintuitive for a smaller first dose to be more effective, they said that strategy may more closely mimic what happens with a real infection,” The New York Times has reported.
AstraZeneca is not testing the six regimens currently as part of the company’s late-stage trial in the US. However, it said it would work with the US Food and Drug Administration (FDA) to add it as quickly as possible. It said it would share its data with the FDA this week. Further, it would begin discussions about whether it would formally submit the findings for review and authorisation.
British regulators have already been conducting a rolling review, as they call it, of the vaccine. “Today marks an important milestone in our fight against the pandemic,”Chief Executive of AstraZeneca Pascal Soriot said. “This vaccine’s efficacy and safety confirm that it will be highly effective against Covid-19 and will have an immediate impact on this public health emergency.”
Chief Investigator of Oxford Vaccine Trial Prof Andrew Pollard said that “these findings show that we have an effective vaccine that will save many lives”.
Pam Cheng, an executive vice president at AstraZeneca, said today if the company were to receive regulatory approval, it would plan to have 4 million doses available in the UK by the end of the year. Globally, by the end of March 2021, the firm said it would have at least 300 million doses of finished vaccine ready for distribution.
Even if not delayed, though, the vaccine is as yet a long way from attaining wide availability. Regulators must assess the study data and decide whether to authorise the vaccine. AstraZeneca must ramp up production and work with government officials to roll out doses.
Besides, in the first weeks and months after regulators authorise the vaccine, it would be available only to the highest-priority groups — doctors, nurses and other health workers first, followed by the most vulnerable groups like the aged people.
Cheng said the first regimen would not significantly complicate the supply chain.
The FDA said it expected a Covid-19 vaccine to prevent disease or reduce its intensity in at least half of the vaccinated people. That is comparable to the effectiveness of seasonal flu vaccines for most years. More interim findings from other leading vaccine makers, including Johnson & Johnson, will be out soon.
AstraZeneca’s vaccine is designed to genetically alter an adenovirus found in chimps so that it harmlessly mimics the coronavirus and provokes an immune response. A vaccine deploying that technology has never won approval. But the approach has been studied before, notably in a small 2018 study of an experimental vaccine against the virus that causes Middle East respiratory syndrome, or MERS. That virus is related to SARS-CoV-2, the novel coronavirus that causes Covid-19.
So when Covid-19 surfaced, Oxford’s Jenner Institute scientists, who had been leading the work on similar coronaviruses, got a head start. Once the genetic code of SARS-CoV-2 was published in early January, the Oxford team sped to adapt their platform to the new coronavirus and begin animal testing.
They also needed a development and manufacturing partner and found one in April in AstraZeneca. Safety testing in Britain began that same month.
In May, the US Department of Health and Human Services pledged up to $ 1.2 billion to help fund AstraZeneca’s development and manufacturing of the vaccine and secure at least 300 million doses if it proved to work.
Alex Secretary of the Department of Health and Human Services M Azar II called the deal “a major milestone” in the work of Operation Warp Speed, the U.S. government’s program to fast-track Covid-19 vaccines.
AstraZeneca has struck deals to supply doses of its vaccine, once authorised, to other wealthy nations, including Britain and other nations in Europe, as well as to lower- and middle- income countries.
AstraZeneca has pledged not to profit from the vaccine during the pandemic, but it has suggested in one of its contracts that it may move to declare the pandemic over by as early as July 2021, The Financial Times reported.
Impact on market
Shares rose on European markets after the announcement. Wall Street futures turned upward. But AstraZeneca’s shares slipped 1.5%.