Threw away its shot

How AstraZeneca threw away its shot

AstraZeneca and the EU might have ruined Africa’s best chance out of the pandemic.

BY JILLIAN DEUTSCH AND ASHLEIGH FURLONG

Adam John Ritchie should be celebrating.

For years, as a project manager at the University of Oxford’s Jenner Institute, he worked to make vaccines for a dollar or two a dose for the globe. The pandemic was his big break, as the university teamed up with Anglo-Swedish pharma giant AstraZeneca to develop one of the world's first coronavirus vaccines.

But over a year and an extra 25 kilos later, Ritchie says, the jab's ill-fated rollout has taken its toll.

“I'm broken,” he said. “Colleagues are broken; we're all broken.” He had already cried once on the day he spoke with POLITICO earlier this month.

The Oxford/AstraZeneca jab, which was once going to save the world, is at risk of becoming a second-tier vaccine. It was supposed to be easy to use, without the need for special freezers — and cheap because its developers, hailed as U.K. national heroes, insisted it be sold at cost.

But after its early green light in the U.K. and the EU, the U.S. never approved it. Many European countries, as well as Canada and Australia, stopped using it in younger people due to blood-clot concerns. Only the U.K. is keen to sign a contract for more (albeit a retooled version). In effect, the world's vaccine has become the Marmite of vaccines.

The implications go far beyond the rich world and are especially devastating to low- and middle-income countries, which remain desperately under-served on vaccines. A toxic mix of developments — fighting between the EU and U.K., caution regarding its use, a botched communication strategy and an over-promising of doses — may have ruined Africa’s best chance out of the pandemic.

Wealthy Western countries, now rolling in mRNA vaccines, are able to write off the Oxford/AstraZeneca jab. But poorer countries are paying the price. One of the most damaging moments was when French President Emmanuel Macron openly disparaged the jab in January, calling it quasi-ineffective.

John Nkengasong, director of the Africa Centres for Disease Control and Prevention, summed up the profound effect of poor communication as it “impacts the confidence that people have in their vaccines, especially coming from authorities, like presidents of countries.”

"The fear factor is out there, the fear of the unknown, the fear of a new virus, the fear of new vaccines," he told POLITICO. "And if we do not spread facts, then it becomes extremely damaging."

Ritchie was even blunter: "Seeing mixed messaging and incorrect information from politicians ... has led to more vaccine hesitancy than there should have been."

Twists and turns

Everything went wrong for the vaccine trying to do right. Early on, a clinical trial mistake raised concerns about the integrity of its efficacy data, and the small number of older people in the trial caused some countries to initially limit its use among the elderly.

The company then failed to deliver on time to almost everyone, which outraged the EU in particular as it began massive vaccination campaigns. Brussels eventually took the company to court for prioritizing the U.K., an alleged breach of contract.

All the while, safety concerns grew over the vaccine's connection with a rare form of blood clots. While the European Medicines Agency took a nuanced approach and declined to prohibit its use, many EU capitals went the other way and blocked it wholesale for younger people.

Even German Chancellor Angela Merkel and Italian Prime Minister Mario Draghi — who made a public show of getting the Oxford/AstraZeneca jab as their first shot to boost confidence — opted for an mRNA vaccine as their second dose.

In the latest setback, many countries now fear the vaccine is less effective against variants, especially Beta, first identified in South Africa. While real-world data from the U.K. shows the vaccine is on par with the BioNTech/Pfizer vaccine at preventing hospitalizations caused by the Delta variant, Beta may be better at evading the effects of the Oxford/AstraZeneca vaccine, researchers warn.

South Africa itself decided not to use the vaccine and infamously sold its doses to other African nations.

These moves may have seriously dented its image just as Europe was starting to give away its unused shots to the developing world, say some experts. The Oxford/AstraZeneca is "a fantastic vaccine" but it's not seen that way, said Walter Ricciardi, a professor at Università Cattolica del Sacro Cuore in Rome.

Blame game

There's no shortage of blame to go around. EU officials and diplomats point out that AstraZeneca over-promised and poorly communicated its problems. One Commission official even suggested that people in the EU died due to AstraZeneca's supply shortages.

"[Oxford/AstraZeneca is] not a second class [vaccine] in terms of its efficacy, it has been a second class as a commercial partner," said Guido Rasi, the former director of the European Medicines Agency.

But the EU played its part. As a former adviser to the Italian government, Ricciardi faulted EU countries for making decisions based on "emotion" rather than science. Scientists and politicians quietly blamed Brexit.

Now, the EU has largely washed its hands of the vaccine. Many EU countries dramatically scaled back vaccination with the viral-vector vaccine, and Denmark and Spain are no longer using it at all. In seemingly altruistic announcements, countries are largely donating the doses. France, which only used the vaccine on over-55s, is now donating the rest of its doses.

But as these excess doses head toward developing countries, the cascading negative press of the past few months is exacerbating the reluctance to accept it. These nations are caught in a bind — highly dependent on the Oxford/AstraZeneca vaccine but increasingly looking to other options.

The think tank Chatham House recently dissected the vaccine's reputational collapse, pinning some blame "at the door of AstraZeneca (and the regulators) for the piecemeal nature of its first Phase 3 trials and its confusing, or even misleading, reporting of the results, as well as the shortfalls in its supplies to the EU."

But the report also noted pointedly that "the apparent politicization of the issue has contributed to public distrust."

Supply squeeze

Incoherent messaging from the West was just one headache for Africa's vaccination drive. It also was hammered in the spring by a supply crisis when the Serum Institute of India — slated to be the primary Oxford/AstraZeneca manufacturer for many low- and middle-income countries — blocked exports and diverted doses to address its home country's devastating surge.

Under COVAX's original scheme, Oxford/AstraZeneca vaccines would come from two separate streams: from SII and from the company directly. But SII was given the responsibility for supplying the vast majority of the poorest countries, explained a development official involved in COVAX. Most of these countries are in Africa.

SII's sudden diversion in the spring, however, left COVAX scrambling to find an alternative, according to the official. The fallback plan was predicated on AstraZeneca scaling up its own production and letting COVAX move doses purchased directly from the drugmaker to those countries without SII doses.

However, that didn't happen. "The AstraZeneca manufacturing network ... is not going to be able to supply in the quantities that would enable us to do that anymore in the short term," the official said. 

Altogether, the impact of delays and shortfalls in deliveries often leads to rumors and misunderstandings. In one country that the development official wouldn’t name, people were told Oxford/AstraZeneca doses were expected. But when supply issues stymied those shipments, the country turned to donations of a different vaccine, leading to confusion.

“That raised a series of questions that couldn't easily be answered at a local level,” said the official. “What lay behind it was constraint in supply, but ... at community level [people assumed] there was a problem with the [AstraZeneca] vaccine.” 

An 'inferior vaccine'?

Peter Waiswa, an associate professor of health policy planning at Uganda's Makerere University School of Public Health, advises the government on immunization. He has seen the pandemic's devastation first hand, with 10 family members contracting COVID-19 and his sister-in-law succumbing to the disease in June.

But even her death, he says, couldn’t convince his family to get vaccinated with the Oxford/AstraZeneca jab, the only one available.

Uganda is one of many African countries that got limited deliveries of the vaccine this spring. But by that point, the bad press had already done its damage. After getting an initial tranche of 864,000 doses in March via COVAX and another 100,000 as a donation from India, the country was able to administer only around 230,000 doses by the end of April.

One reason for such sluggish uptake was that the virus itself wasn't considered widespread at the time, Waiswa explained. But making matters worse was that the European controversy over vaccine safety was spilling over to Africa.

A further setback happened in late June, when news broke that some EU countries wouldn't recognize the version of the Oxford/AstraZeneca vaccine made by SII. That decision effectively cut off many vaccinated travelers from South Asia and Africa — while confusing the situation further on the ground.

"People have been asking whether this means we are getting an inferior vaccine," Waiswa said, pointing out that AstraZeneca gave its formula to SII, ostensibly to produce the same jab.

Still, the one silver lining to the skyrocketing cases in the past months is that they've made the decision easier for many, Waiswa says, pointing to a “mad rush” for the vaccine after cases began to increase in May. But many people with first doses are now left waiting anxiously for further deliveries, with Uganda having received only about a third of the total doses it had expected from SII through COVAX by the end of June.

With SII still not exporting, the country has relied on donated doses from France. It's also waiting on a shipment of 688,800 doses from COVAX that consists of Oxford/AstraZeneca doses not produced in India to cover second doses.

Overstretched

Massive delivery shortfalls continue to stymie Africa's vaccination drive. According to the latest Africa CDC’s data, just over 1 percent of the population in Africa is fully vaccinated. The continent is tens of millions of doses behind other regions and has relied largely on COVAX, which has delivered just 40 percent of the doses it was expected to have distributed around the world by the end of June. 

The stretched supply and distribution problems are exacerbating vaccine hesitancy, as Malawi's experience shows. 

In May, media reported a jarring scene as health officials publicly burnt 20,000 Oxford/AstraZeneca doses that were three weeks away from expiration — even though less than 2 percent of the population had gotten one dose at that point. It had used just 80 percent of its stockpile, and authorities wanted to make the point that expired doses wouldn't be distributed, the country’s health secretary told the BBC. 

This episode also pointed to a broader problem: Inconsistent and sporadic deliveries of vaccines will undermine confidence if governments grapple with questions like when to send out new communication materials, when to train health care workers and when to plan for an expansion of the vaccine program, explained the development official involved in COVAX. 

But a looming virus surge in Africa has meant that countries have had to take what they can get — and in most cases, that’s small quantities of the Oxford/AstraZeneca vaccine. 

On their own

Left with few good options, Africa is looking elsewhere for new vaccines. One of those could be the single-shot Johnson & Johnson jab, which also has the advantage of simpler storage requirements. The African Union’s African Vaccine Acquisition Task Team has already secured an agreement for up to 220 million doses of the one-shot jab.

“When things pick up ... [the Johnson & Johnson vaccine] will become the predominant vaccine on the continent because of the ease of use," said Africa CDC’s Nkengasong. "It's the most suitable programmatic vaccine."

There's also hope that just as EU countries have largely relied on mRNA vaccines, Africa could also pivot in that direction.

"A key driver to accelerate vaccine uptake in Africa is to upgrade the cold chain capacity to be able to store and handle messenger RNA vaccines," said Phionah Atuhebwe, who serves as vaccines introduction medical officer in the WHO's Africa office. Fifteen countries already have these facilities, including Rwanda, Uganda and South Sudan.

Where those cold chains aren’t in place, countries are looking at another scheme in which multiple small shipments are distributed on the ground within the 31-day-period that the BioNTech/Pfizer vaccine can be kept at refrigerator temperature. 

For their part, Oxford scientists have not given up hope on their vaccine. They are testing a retooled version that targets variants, as well as booster shots in case either are soon needed. Oxford's Ritchie also is looking at making a version of the vaccine that could be inhaled, which could require less drug substance and possibly be used to stretch vaccine supply around the world. 

It's projects like this that motivate Ritchie to get out of bed every morning.

"I’m never in my life going to have an opportunity to save thousands or millions of lives," Ritchie said. "This is my one shot, and my colleagues’ one shot of doing that.

“But we're tired,” he admitted. 

Ritchie is also upset. He believes AstraZeneca was used as a “scapegoat” at a time when the EU was struggling to ramp up vaccinations. Macron calling the vaccine quasi-ineffective will "stick forever," he adds. And he calls the EU’s lawsuit against the drugmaker "morally untenable" given that the company is producing the most vaccines for the globe.

But there's still the hardest pill for Ritchie to swallow: What do all these setbacks mean for his life-long goal of making vaccines affordable and accessible around the world?

"The thing that terrifies me more than anything else is that the one vaccine that's not-for-profit is the one that has been dumped on over and over and over again," he said. He points out that no other drugmaker offered to produce at such a low cost — even Pfizer got the U.S. government to offset its costs to supply COVAX.

He made clear he doesn't represent AstraZeneca or make decisions for the company, but if he did, "I would not sign up for a deal like this ever again."

“Who is going to sign up to do nonprofit supply ever again?" he asked.