AstraZeneca’s Covid-19 vaccine shows better-than-expected efficacy in U.S. trial

AstraZeneca said Monday that the Covid-19 vaccine it developed with the University of Oxford reduced both mild and serious forms of the disease, paving the way for a likely U.S. authorization of the vaccine.

Doctors, regulators, and government officials the world over are likely to breathe a sigh of relief at the results, which are better than expected and appear materially higher than those in previous studies. 

The two-dose vaccine reduced symptomatic disease by 79%, the company said in a press release, and reduced severe Covid-19 and hospitalization by 100%. AstraZeneca said that the vaccine was equally effective in people over 65, where it had 80% efficacy.

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Two volunteers in the study received vaccine for every one that received placebo. Across the study, 141 had symptomatic Covid-19 and five, all in the placebo group, had severe disease. Mene Pangalos, the executive vice president of biopharmaceutical R&D at AstraZeneca, said on a call with reporters those figures made the company very confident about the results, but that more data are being collected from the study.

The company said the study identified no new safety concerns. A specific review found no risk of blood clots, worries about which led many European nations to pause their vaccine rollouts last week. The European Medicines Agency said last week the vaccine’s benefits outweighed its risks. The study also did not see a specific type of clot in blood vessels near the brain that the EMA said might be associated with the vaccine. However, this type of clot, called a cerebral venous sinus thrombosis, is so rare it might not be expected to occur in even a large clinical trial.

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“This analysis validates the AstraZeneca COVID-19 vaccine as a much-needed additional vaccination option, offering confidence that adults of all ages can benefit from protection against the virus,” said Ann Falsey, a professor of medicine at the University of Rochester School of Medicine, in the press release.

AstraZeneca plans to request an emergency use authorization from the Food and Drug Administration, and said it is preparing for “the rollout of millions of doses across America.”

The results are from an interim analysis of a 32,000-volunteer study conducted in the U.S., France, Chile, and Peru with funding from the U.S. Biomedical Advanced Research and Development Authority and the National Institutes of Health. Details in the AstraZeneca press release are sparse, even compared to press releases made by other vaccine makers. Full results will likely be published in a medical journal, and released in even more detail as part of the public vetting process of the FDA.

AstraZeneca’s results are “surprisingly positive,” Peter Welford, a pharmaceuticals analyst at the investment bank Jefferies, wrote in a note to clients. A previous analysis of four large studies of the vaccine in the United Kingdom, South Africa, and Brazil, showed the vaccine had efficacy of about 60%. Welford argued that the efficacy compared favorably to previous vaccines, especially given the prevalence of new variants of the SARS-CoV-2 virus, which causes Covid-19, that may decrease efficacy. Previous studies have hinted, he noted, that the vaccine could be more effective if doses are given further apart. The current study, like previous studies, gave two doses one month apart.

Among volunteers in the study, 79% were white, 22% were hispanic or LatinX, 8% were Black, 4% were Native American, and 4% Asian. About 20% of participants were 65 years and over, and approximately 60% had other health problems that can worsen Covid-19 like diabetes, severe obesity, or heart disease.

Even before AstraZeneca’s involvement, researchers at Oxford University had an ambitious goal: to create a vaccine that could be available to large swaths of the global population. The shot they designed is less expensive than other vaccines, and easier to manufacture and distribute. Unlike the Pfizer and Moderna shots, which must be kept very cold, it can be stored for six months at between 2 to 8 degrees Celsius and administered without on-site preparation.

Steps have already been taken to enlist other manufactures, including the Serum Institute of India, to make large amounts of the vaccine. The vaccine has been broadly deployed in the United Kingdom, which has vaccinated half its population.

But studies of the vaccine have been plagued by mishaps. Early on, the U.S. study was stopped for a month-and-a-half because of a cerebral hemorrhage in one patient that was later determined to be unrelated to the vaccine. Later, early trial results in the U.K., South Africa, and Brazil left many experts scratching their heads, as the second dose of the vaccine seemed to decrease its efficacy.

South Africa halted its own rollout of the vaccine in February after a small study showed the two-shot vaccine might not be as effective against a new variant of the coronavirus that causes Covid-19 that is circulating there. 

The two-dose AstraZeneca vaccine, like the one-dose vaccine developed by Johnson & Johnson, uses a modified common cold virus, known as an adenovirus, to ferry genetic code for a key component of the SARS-CoV-2 virus known as the spike protein into recipients’ cells. The cells make this protein, which is then recognized as foreign by the immune system. The result is that the recipient becomes protected against the virus.

Earlier vaccines from the team of Moderna and Pfizer/BioNTech use a different technology, called mRNA, in which particles of messenger RNA are snuck into cells, and also make versions of the spike protein.

The new efficacy result compares favorably with the results seen in studies of other vaccines, although it is impossible to directly compare the vaccines because they used different criteria for deciding whether to give Covid-19 tests to patients and because they were conducted at different times when different variants of the SARS-CoV-2 virus may have been circulation.

Last November, Pfizer and BioNTech released data showing that its vaccine was 95% effective at preventing symptomatic disease. That clinical trial tested patients for SARS-CoV-2 whenever they had a symptom that might indicate they had the disease. There were only nine cases of severe disease in the study, all but one were in the placebo group.

Moderna and the NIH also released results in November showing the vaccine reduced symptomatic Covid-19 by 94%, but it required volunteers two symptoms to be tested. In its study, there were 30 cases of severe disease, all in the placebo group.

On Jan. 29, Johnson & Johnson and the NIH reported that J&J’s vaccine, the only one to require only one dose, prevented moderate Covid-19 by 66%, with results differing by geography due to different variants being in circulation. It reduced severe disease by 85% — there were 30 cases in the placebo group, but one in the vaccine group. The J&J vaccine also prevented death from Covid-19. There were seven deaths due to Covid in the placebo group, and none in the vaccine group. In other studies, not enough patients died of Covid to make that comparison.

All three of those vaccines were granted emergency authorization in the United States.

NovaVax has also released results showing 90% overall efficacy of its vaccine in a study in the U.K. In a separate trial in South Africa, where the B.1.351 strain is circulating, the efficacy was 49%. The vaccine still prevented severe disease in South Africa, with no cases in the vaccine group and five in the placebo group. All five of those patients were hospitalized, and two died, the company said on March 11.

One question for the AstraZeneca vaccine will be how new variants of the SARS-CoV-2 virus affect the vaccine’s efficacy. The data from South Africa, released in February and published in the New England Journal of Medicine last week, showed only limited vaccine efficacy. It’s not  clear how much the data from the current study can offer regarding those variants, which have been most common in South Africa and Brazil.

Still, the results are encouraging, meaning that one of the world’s most-used Covid-19 vaccines is also an effective choice.

Source: STAT