It was billed as the vaccine to deliver the world from Covid. But over the last six months, AstraZeneca – whose jab was designed to save thousands of lives for no profit – has found itself stumbling along an extraordinarily rocky road, facing accusations over the efficacy, supply and side-effects of its vaccine from all quarters, and being kicked about like a political football.
This week, AstraZeneca faced unprecedented public criticism in the US from a high-level scientific body claiming the British-Swedish company massaged the data from its long-awaited trial there. And in Italy, military police entered a factory on behalf of the European commission investigating allegations of 29m hidden doses, said to be intended for shipment to the UK. The commission, which is demanding AstraZeneca supplies more jabs to Europe, meanwhile drew up regulations which could block vaccine exports to the UK.
Alleged politicisation of the Oxford/AstraZeneca vaccine is particularly evident in Europe where the distribution of jabs has trailed well behind progress in the UK. One UK government source suggested the raid on the Italian factory – which turned out to hold doses for Belgium and the developing world awaiting quality checks – was embarrassing for those “who tried to whip up an anti-AZ mob because it gives them political cover”.
At the start of this year, it looked as though post-Brexit animosity might lie behind the sniping. On 25 January, the German newspaper Handelsblatt caused a storm with a front-page story claiming the vaccine had only 8% efficacy in the elderly. On 29 January, France’s president Emmanuel Macron claimed it was “quasi-ineffective” in the over-65s. Germany and France refused its use in that age group. Although those restrictions have been lifted, many in those countries are reluctant to have the vaccine.
Now, facing a third wave in Europe, low uptake and criticism from French doctors who accused him of encouraging vaccine hesitancy, Macron has done a volte-face, saying he would be happy to be inoculated with it himself, while the prime minister, Jean Castex, had the AstraZeneca jab live on TV.
Yet still the flak flies. Belgian MEP Philippe Lamberts has this week accused the company of dishonesty and arrogance. It had “over-promised and under-delivered”, he said, and hinted there were still issues with safety even though the European Medicines Agency has given it a clean bill of health.
Embattled scientists at AstraZeneca feel they have been unfairly targeted for trying to do something that goes against the profit-driven grain in the pharmaceutical industry – produce a low-cost, easy to use vaccine that will work well for low and middle-income countries but will not make them money in the short-term.
Sir John Bell, the Oxford University professor who helped drive the vaccine’s development, suggested morale at AstraZeneca is plummeting and that it had never received due credit for its decision to take no profit. Others are making fortunes – Moderna expects $18bn in revenue this year from the vaccine and Pfizer/BioNTech $15bn.
Citing the attack from Macron and unfounded accusations over safety and efficacy, Bell said the company could re-think its philanthropic stance. “There’s a point at which AstraZeneca could just say, ‘you’ve got to be joking, we’re going to stop [charging cost price] now because we’re not getting any credit for what we’re doing. The share price has gone down, not up. We’re making more vaccines than everybody else. This is a safe and effective vaccine, but nobody seems to care,” he said this week.
It’s hard to point to one single reason why AstraZeneca should be constantly on the back foot, but their woes date back to September last year when their trials were halted because of a reported adverse reaction in the UK, which turned out to be transverse myelitis – inflammation of the spinal cord.
If there is a common thread, say critics and some friends alike, it is a failure to communicate well. The UK regulator gave the go-ahead to restart trials within days, but the Food and Drug Administration, which approves drugs in the US, maintained the suspension for a full six weeks. They were unhappy not to have been told of the problem promptly enough, it emerged, and dissatisfied with the company’s explanations.
But the Oxford/AstraZeneca team also failed to keep things simple. Drug regulators dealing with profit-making pharma companies are used to seeing data from one big trial which ticks all the boxes for age, ethnicity, state of health and other factors that could skew results. Pfizer/BioNTech and Moderna did just that and came up with one big impressive number for efficacy – around 95%.
Oxford/AstraZeneca did not. Oxford University’s scientists who initiated the early trials were academics, investigating the best way to prevent this disease.
“I think that some of the difficulties were that the trials were being set up by Oxford to answer public health questions, whereas very clearly Pfizer/BioNTech and Moderna’s trials in the US were set up to get FDA approval,” Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, told the Guardian.
Oxford/AstraZeneca came up with two numbers, not one: 62% efficacy overall and 78% in people who had originally received a half dose because of a supply issue. Industry analyst Dr Adam Barker of Shore Capital said people forgot the hope was for a 50% effective vaccine and compared the results to Pfizer’s. It didn’t help that the reason for the higher number was later reinterpreted as a longer gap between the two doses. Nor that older people were late to be recruited into the trials because of Oxford’s ethical concerns. Infections dropped in the UK over the summer so fewer died, which meant there was not much data on how well it worked in the over-65s.
“There’s no doubt that setbacks and confusion over data interpretation and and all the noise that we’ve seen impacts trust in vaccines,” said Barker.
Communication seems to be key to the spat with the data safety and monitoring board (DSMB) in the US – the independent scientists who watch over trials. Usually, said Evans, “the DSMB is a very private group. You don’t let on who is on it, so they can’t be pressured”. It’s highly unusual for them to go public. Yet on Monday night, less than 24 hours after AstraZeneca had reported the success of the vaccine in the US trials, the DSMB said the company had presented “outdated and potentially misleading” data to the world.
Once again, it seems to have been a pointless row. The company says the agreed cut-off point for data was 17 February, by which time there had been 141 cases and efficacy was 79%. Within 48 hours, AstraZeneca had added more recent data. On a total of 190 cases, there was 76% efficacy (and as always 100% against severe illness and death). It’s not much of a difference.
No other Covid vaccine manufacturer has had the bad publicity AstraZeneca has suffered. Its vaccine was suspended in some European countries over blood clots, even though there have been similar reports with all of the vaccines and one death is being investigated, linked to Moderna’s jab, in the US. Nor has supply been straightforward for other vaccines. Pfizer has had dips in production and Johnson&Johnson and Novavax have warned that supply may be lower than they originally thought.
But AstraZeneca is under extreme scrutiny all the time. It may be because of its professed desire to save the world. It may be because one or two missteps make everybody look for others. It may be because it attracts political flak as a proxy for the UK, especially in a post-Brexit world. Whatever, Oxford University and the company will now be hoping that the accumulating evidence of how well the vaccine works in the real world causes the heat to die down – although they may have to solve the supply issues first.