LONDON – A third COVID-19 vaccine has turned in positive results in the phase III interim analysis, with Astrazeneca plc/Oxford University reporting an average of 70.4% efficacy across two dose regimens for AZD-1222.
Significantly, efficacy increased to 90% in the prime-boost arm of the trial, in which volunteers received half a dose, followed by a full dose. In addition to greater protection, that will make supplies go further.
Adding to the positive findings, there were no cases of severe disease or need for hospitalization in vaccinated people who did contract COVID-19, and there are early indications that AZD-1222 reduces transmission of the virus, as seen in the fact that there were fewer asymptomatic infections in the vaccinated arm.
“The results mean we’ve got a vaccine for the world,” said Andrew Pollard, director of the Oxford Vaccine group and chief investigator for the phase III. “It’s highly effective and prevents severe disease and hospitalization.”
Researchers at Oxford University are stressing that they designed AZD-1222 from the ground up to fit existing global vaccines infrastructure, and the vaccine can be stored at fridge temperatures of between 2 and 8 degrees centigrade and distributed using existing logistics.
“The vaccine can be stored at fridge temperatures and so can be distributed around the world. The goal was to have a vaccine that is accessible everywhere,” Pollard said.
The safety and efficacy data are due to be submitted immediately to the EMA and the U.K. Medicines and Healthcare products Agency, which have been conducting a rolling review. Astrazeneca also will seek emergency use listing from the World Health Organization to accelerate availability in low income countries. “The job now is to work with regulators around the world as rapidly as possible,” said Mene Pangalos, executive vice president of biopharmaceuticals R&D at Astrazeneca.
The 131 positive cases of COVID-19 infection in the study population that triggered the interim analysis, are up to Nov. 4. Pollard said there is much more data to follow, but the existing file that will be submitted already is equivalent to 6,000 years of follow up. “That is a huge amount of data, usually it is 3,000 to 5,000 [years] that is required for vaccines in Europe,” Pollard said.
And that is before adding in the findings of separate trials Astrazeneca is running in the U.S., Kenya, Japan and Russia, and which one of the manufacturing partners, Serum Institute of India, is running in India.
“The size of the safety database is going to be very large. The key point is what the regulators will do as they go through it in detail,” said Pollard.
Preventing mild disease, too
Manufacturing of commercial supplies is in progress in 10 countries, with Pam Cheng, executive vice president of operations and information technology at Astrazeneca, saying 3 billion doses will be available next year. How far that goes depends on the dosing regimen, but Cheng said the supply chains are set up to cope with either, or both schedules.
Sarah Gilbert, professor of vaccinology at Oxford University, on whose research the chimpanzee adenovirus vector technology is based, said, “This didn’t just come out of nowhere; it’s something we’ve been doing for some years, working on a way of making vaccines efficient, and [the vector] is very adaptable. For some years, we’ve been using it to make vaccines against other infections [….] and had already done clinical trials with a human coronavirus [MERS], so we knew we could get a good immune response against spike protein.”
“The vaccine’s simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available, supplying hundreds of millions of doses on approval,” said Pascal Soriot, CEO of Astrazeneca. “No cases resulted in hospitalization; it’s a really exciting result.”
It is unclear as yet why the prime-boost regimen elicited a greater immune reaction. “All of us expected two full doses would give a better response,” said Pollard. He speculated that the greater effect seen when initially administering half a dose was a result of SARS-C0V-2 being a new virus that no human immune system had seen before. A similar phenomenon is seen in babies, he noted.
At this stage, it also is uncertain if the greater response is more of the same as occurs with two full doses, or if the prime-boost regimen induces a broader spectrum response. “We think by giving a smaller first dose, it is priming the immune system better. We’re going to be digging into this. We’ve already started some work this morning, having only just seen the results,” said Pollard.
The U.S. trial that is being run by Astrazeneca has recruited 10,000 to 11,000 volunteers on the two full-dose regimens. Pangalos said the company will now talk to the FDA about starting an arm with half dose/full dose.
Pollard was not able to say why AZD-1222 shows a lower response than Moderna Inc.’s and Pfizer Inc/Biontech SE’s mRNA vaccines, which have shown 95% efficacy. However, he noted, “We know from the protocols, they are measuring different things.” If the primary endpoint of the AZD-1222 phase III had been to reduce severe disease and hospitalizations, the result would have been higher. “We are trying to [prevent] mild disease as well, which is difficult,” said Pollard.
It should become clearer once full data are published. Pollard said the AZD-1222 interim phase III results will be submitted to a peer review journal “within the next 24 hours.”