AstraZeneca : Vaccine Trial Data Underscore Safety, Range of Efficacy -- 2nd Update

By Jenny Strasburg and Joseph Walker

LONDON -- Peer-reviewed data from late-stage human trials of a Covid-19 vaccine developed by the University of Oxford and AstraZeneca PLC reaffirmed the shot's strong safety results and provided some additional evidence that halving the first of two doses of the shot boosts its effectiveness.

AstraZeneca and Oxford said the data gave them confidence to ask the U.K. and other countries for emergency-use authorization of the vaccine, but said regulators will have to decide which dosing regimen to approve. Last month, AstraZeneca and Oxford said trial data showed the vaccine was between 62% and 90% effective, but that the higher results were observed in a small subset of the wider trial.

This subset received a half-sized initial dose followed by a full second dose. The group was also all under 55 years old, raising questions about whether the lower dosing would also be effective in older subjects.

AstraZeneca and Oxford on Tuesday declined to say whether they would ask regulators to approve the lower-dose regimen, leaving unclear whether an initial vaccine approval and rollout would be limited to the less-effective regimen. The 62% effectiveness shown in the majority of the trial participants is still better than what health experts deem necessary to protect people against severe Covid-19.

The publication of the data in the Lancet -- the first full peer-reviewed results from any of the late-stage human trials disclosed so far by the West's three leading vaccine makers -- comes on the day that a vaccine developed by Pfizer Inc. and Germany's BioNTech SE was being administered for the first time outside trials, in the U.K. The country authorized the vaccine for emergency use last week.

It also coincided with a preliminary assessment by the U.S. Food and Drug Administration on Tuesday showing the agency was satisfied with the Pfizer shot's effectiveness and safety, paving the way for a potential emergency-use authorization in the U.S. in coming days.

The FDA is also reviewing Moderna Inc.'s vaccine, with a verdict expected shortly.

While those two vaccines have raced ahead of AstraZeneca's in the U.S. regulatory process, much of the rest of the world is betting on latter. Oxford and AstraZeneca have promised to provide many more doses across a wider geographic footprint then either Pfizer or Moderna.

The partners also promised to provide the shot at cost, making it the vaccine of choice for much of the developing world.

Results from an ongoing U.S. study will likely be needed before a potential approval in the U.S., said Menelas Pangalos, AstraZeneca's head of biopharmaceutical research, citing conversations with regulators at the FDA.

The U.K. government already has asked its medicines regulator to review AstraZeneca's shot for emergency-use authorization. The published results push the vaccine closer to a potential rollout in Britain, while late-stage trials of the shot continue in the U.S.

"We hope to see regulatory approval in the coming weeks," Sarah Gilbert, an Oxford vaccinology professor and a lead scientist on the vaccine, said on a call with reporters.

The researchers continue to collect data from the studies and expect to have more answers in the future about differences in the effectiveness of the two regimens and between age groups, said Prof. Gilbert.

AstraZeneca has described the half-dose results as the product of a lucky error in calibrating dosage in the early stages of human trials, but that it is still trying to understand the surprising result. An Oxford scientist said Tuesday that the half-dose was unplanned but that the study design was amended to include the half-dose group in its analysis. Both said the half-dose regimen will be tested further.

The Lancet study authors said further analysis in recent weeks has been promising: They said they found that the change in dosage -- not age or another factor -- appears to cause the 90% effectiveness. That determination came after a deeper analysis of the data to isolate the effects of the half-dose from other differences between trial volunteers. The Lancet authors said more study was needed to make a determination. A standard schedule of two full doses was shown to be 62% effective, the same as the vaccine partners said two weeks ago.

The effectiveness results are based on late-stage trials involving more than 11,600 people in the U.K. and Brazil. Tuesday's data contained more information than previous results about the safety of the vaccine, including data from trials involving more than 23,700 participants in the U.K., Brazil and South Africa.

Of those, three participants experienced serious adverse events, including one person who received the vaccine and 14 days later developed what was reported to be a case of transverse myelitis, a neurological disorder. Independent investigators monitoring the study said it possibly was related to the vaccine but couldn't determine that for certain. Regulators allowed trials to resume following the independent evaluations.

The 62% effectiveness clears the 50% hurdle set earlier this year for emergency authorization of Covid-19 vaccines by regulators including the FDA. That hurdle is in addition to requirements for safety and manufacturing quality.

The peer-reviewed data showed the vaccine provides protection against severe Covid-19 disease, a promising result that could help ease the burden on hospitals. The Oxford-AstraZeneca vaccine appears to protect against transmission of the disease by people not showing symptoms, though scientists said they need more data to confirm the findings.

Scientists involved in the vaccine, including AstraZeneca executives, said that even at its lowest effectiveness, the vaccine can be a crucial tool in fighting the pandemic, along with other shots and treatments.

"Personally I think we need to be completely agnostic about which vaccine is being used, because we need multiple vaccines as soon as possible," Prof. Andrew Pollard of Oxford, a lead scientist on the vaccine study, said. "Otherwise we'll still be in this position in six months' time."

But some other researchers said they would like to see more data to know how effective the vaccine is in older adults and in nonwhite groups disproportionately affected by the disease. The trials started off in younger, lower-risk groups. Also, some researchers have concerns that the vaccine's baseline 62% effectiveness -- while helpful in keeping people out of the hospital -- could be insufficient to stop the virus from spreading.

The Oxford-AstraZeneca vaccine's 62% effectiveness reading fell short of results from Moderna, at 94.5%, and Pfizer, at 95%.

Write to Jenny Strasburg at [e-mail] and Joseph Walker at [e-mail]

(END) Dow Jones Newswires

12-08-20 1312ET