The Covid-19 vaccine being produced by AstraZeneca is effective, the company said Monday, bringing closer to approval a vaccine that may be easier to distribute and less expensive compared to rival candidates.
The vaccine was 70% effective on average—and up to 90% effective under its most favorable dosing regime—across clinical trials conducted in both the U.K. and Brazil, the company said.
The trials used two different dosing regimes, which seems to have generated markedly different effectiveness rates. The vaccine was 90% effective if people received a half-dose followed by a full-dose one month later—and 62% effective if people were given two full doses one month apart, the company said.
Regulators in the U.S. have set a threshold of 50% effectiveness for any vaccine they approve. AstraZeneca said it would seek approval for its vaccine from a variety of global medical regulators, including in the U.K. and European Union.
Mene Pangalos, AstraZeneca’s executive vice president of biopharmaceuticals research and development, said the company would be in contact with the U.S. Food and Drug Administration this week to see if they might consider granting emergency use authorization for the vaccine based on this data, or if the agency will say it wants further information from late stage clinical trials the company is conducting in the U.S.
A dose and a half
There were no serious safety events related to the vaccine in the clinical trials, which included more than 23,000 people, the company said.
The company also said that both dosing regimes seemed to prevent serious cases of Covid-19 in which people wind up hospitalized. There were no cases of people sick enough to be hospitalized among those inoculated, AstraZeneca said.
Sarah Gilbert, a researcher at the University of Oxford’s Jenner Institute, which developed the vaccine in conjunction with AstraZeneca, said there was some evidence from those who received a half-dose followed by a full dose that it could also prevent mild and even asymptomatic disease.
Investors were apparently unhappy AstraZeneca was reporting a lower overall efficacy figure than those reported in recent weeks by pharmaceutical company Pfizer and biotech firm Moderna, both of which said their Covid-19 vaccines had been found to close to 95% effective in clinical trials. AstraZeneca’s shares on the London Stock Exchange were down 1.75% in early morning trading following the announcement.
Refrigeration, expense, and dosage
But the vaccine being produced by AstraZeneca has some significant practical advantages over Pfizer and Moderna’s vaccines. For one, it can be stored between two and eight degrees Celsius (35.6 to 46.8 degrees Fahrenheit), which is within the range of normal refrigerators.
The rival vaccines have different underlying technology and must be kept at super-freezing temperatures: Pfizer has said its vaccine needs to be kept at negative 70 Celsius (-94 Fahrenheit), while Moderna has said its vaccine can be kept at negative 20 Celsisus (-4 Fahrenheit.) That means they will be more difficult and expensive to transport and store.
The AstraZeneca vaccine is also expected to be far less expensive than either Pfizer’s or Moderna’s. The company, which has pledged to make no profit on the vaccine during the period of the pandemic, has priced the vaccine, according to some reports, at less than $5 per dose. In contrast, Moderna has priced its vaccine above $35 per dose; Pfizer has set an initial price just below $20 per dose.
Because the most effective dosing regime was found to be one in which people received just one-and-a-half doses of the vaccine in two separate injections, the company also said this would allow more people to be immunized using its vaccine than it had initially thought might be the case if people had required two full doses.
300 million doses globally
Pascal Soriot, AstraZeneca’s chief executive officer, called the announcement of the efficacy results for his company’s Covid-19 jab “an important milestone in our fight against the pandemic.”
The company has made arrangements to manufacture up to 3 billion doses of its vaccine in 2021. The U.S. has contracted to receive up to 300 million of these, the U.K. 100 million, and the European Union up to 400 million. It has also committed to providing 300 million doses to low- and mid-income countries through an agreement with the Coalition for Epidemic Preparedness Innovations (CEPI) and the vaccine funding body Gavi, and has signed other agreements to supply doses to several other nations.
Pam Cheng, AstraZeneca’s executive vice president for global operations and information technology, said that the company would have 4 million finished doses of the vaccine ready for use in the U.K. by the end of the year and 40 million by the end of the first quarter. She said that AstraZeneca would have 300 million finished doses ready to be used globally in that same time frame.
Priming the immune system
The AstraZeneca vaccine uses a genetically-modified chimpanzee virus that has been rendered harmless to prompt the body’s immune system to produce antibodies and T-cells that can target SARS-Cov-2, the virus the causes Covid-19. This is in contrast to the vaccines from Pfizer and Moderna, which both used genetically-modified messenger RNA (or mRNA), to directly instruct the body’s cells to produce a protein found on the surface of the coronavirus.
Andrew Pollard, a researcher at the Oxford Vaccine Group, which collaborated with Oxford’s Jenner Institute on running the clinical trials of the vaccine in the U.K., Brazil and South Africa, said it was not clear yet why a half-dose injection followed by a full dose inoculation seemed to be more effective than two full doses. “We think the smaller first dose primes the immune system differently,” he said, noting that this was often the case in vaccines given to infants, where a smaller initial doses made a subsequent booster much more effective.
But he added that the researchers were not yet sure in the case of the Covid-19 vaccination if this is a case of the initial half dose prodding the body to produce more antibodies and T-cells or, if instead, the difference was one of “quality”—where various parts of the immune system were better configured to target the virus after the initial half-dose shot.
Scientists not affiliated with the vaccine project hailed the results, while sounding a note of caution about the difference in the efficacy figures between the two dosing regimens. Stephen Griffin, a professor of medicine at the University of Leeds, said the news was “tremendously exciting.” He said that “while it may seem confusing that a higher initial dose gives a less favorable response,” this might be because some people had a strong immune response to the initial dose of the disabled chimpanzee virus that is used to deliver the vaccine, and that this strong response made the booster less effective.
Ian Jones, a professor of virology at the University of Reading, also speculated that the reduced effectiveness of the two full doses was the result of an immune response to the modified chimpanzee virus technology that AstraZeneca is using. He said this may be an indication that mRNA vaccines, which directly provide instructions to cells to make a protein that then prompts the immune response, may have an advantage over those that use a different virus to deliver those instructions.
“There is no vector in either the BioNtech/Pfizer or Moderna vaccines so the issue of immunity to the vector does not arise,” he said. But he also noted that the AstraZeneca vaccine had advantages in terms of storage and AstraZeneca’s commitment to not making a profit from the vaccine initially.
Potential changes to U.S. Stage III trial
There were about 3,000 people in the clinical trial arm that used the half-dose followed by the full dose booster, Pollard, from the Oxford Vaccine Group, said. He said this was enough people to make the results from this group statistically significant. He said Oxford would be publishing figures for exactly how many of the 131 Covid-19 cases recorded across both clinical trial groups were in that particular arm of the study.
AstraZeneca’s Pangalos said the company would discuss with the FDA whether to switch its large Phase III U.S. clinical trial over to a half-dose and then full dose regimen too. Currently that trial, which is expected to ultimately enroll 40,000 people, is set up using two full doses. He said about 10,500 people have already received an initial full dose in that trial so far.
He said it was possible that other regulators around the world will wind up approving the vaccine for use based on these trial results while the U.S. withholds approval until the vaccine can be proven in the U.S. trial.