Tuesday, March 21, 2023

US Agency Questions AstraZeneca COVID-19 Vaccine Trial

AstraZeneca might have included outdated information from a clinical trial of the Covid-19 vaccine it has developed with Oxford University, a US federal health agency said on Tuesday, throwing previously published positive results into doubt.

In a rare move, the National Institute of Allergy and Infectious Diseases said it had been notified by the trial’s data and safety monitoring board that “it was concerned by information released by AstraZeneca on initial data from its Covid-19 vaccine clinical trial”.

“The DSMB expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data,” the NIAID said. The group is led by Anthony Fauci, an adviser on coronavirus to the US president.

The NIAID said it had urged AstraZeneca “to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible”.

AstraZeneca and Oxford university did not immediately respond to requests for comment early on Tuesday.

Shares in AstraZeneca fell at least 1.2 percent shortly after the London stock exchange opened on Tuesday morning.

London-listed shares in the Anglo-Swedish drugmaker had closed 3.3 percent higher on Monday after the results from the long-awaited American trial of the Oxford/AstraZeneca vaccine were released. More than 32,000 volunteers took part, mostly in the US, but also in Chile and Peru. A fifth of the participants were over 65.

The trial showed the vaccine was 79 percent effective at stopping symptomatic Covid-19 and 100 percent effective at preventing people from falling seriously ill.

The company said there were no safety issues regarding blood clots. Earlier reports of side effects from taking the vaccine, including a rare combination of clots in the brain, bleeding and low platelets, had prompted at least 16 European countries to suspend the use of the jab.

Most have now resumed its use after the European Medicines Agency said it found no link between clotting and the vaccine. The drug watchdog left the door open to a link between the vaccine and the rarer combination of side effects but has said throughout the crisis that the vaccine’s benefits far outweigh its risks. The combination is so infrequent that the US trial would have been unlikely to be able to detect any such events with its sample size.

It is not the first time data on the AstraZeneca Covid-19 vaccine have been questioned. The company and the university also faced criticism in November for the way they handled the disclosure of the first phase-3 results for the vaccine.

Most of the controversy hinged on the results of two different dosing regimens that yielded a pooled efficacy figure of 70 percent — 62 percent for patients taking two full doses, and 90 percent for those taking a half-dose and a full dose.

But the half-dose, the full-dose regimen was eventually abandoned after the UK drugs regulator approved the vaccine in December, saying it was not borne out by full analysis.

Experts also said the higher-efficacy cohort only included people aged 55 or below, a fact that was not immediately disclosed. Analysts had said it was unlikely the US Food and Drug Administration would grant approval based on that data set.

Monday’s American trial had been seen as a significant opportunity for the drugmaker to reverse its fortunes in the US, though the NIAID warning has damped those hopes.

Stephen Evans, a pharmacoepidemiology professor at the London School of Hygiene and Tropical Medicine, noted DSMBs sometimes disagreed with investigators over the interpretation of trial results. But he said: “It is usually done in private, so this is unprecedented in my opinion.”

The AstraZeneca shot — easy to store and transport, and currently sold at cost — forms the backbone of many vaccination strategies globally, with the EU, the US, and the World Health Organization-led procurement effort Covax having placed large orders of the jab.

The UK has also given it to millions of people, with real-world evidence suggesting a significant effect in cutting deaths and hospitalizations related to Covid-19.