Where Did it All Go Wrong for AstraZeneca?

It was supposed to be pharma’s crowning glory. The industry did what many thought was impossible: developed and approved an effective vaccine against COVID-19 in a matter of months. Perhaps even more remarkably, AstraZeneca did it all while pledging not to make a profit. While organizations such as Médecins Sans Frontières have requested transparency regarding the pledge (1), and the Financial Times reported that AstraZeneca has defined the pandemic period as ending on 1 July 2021 – potentially opening the door to future price hikes (2) – the AstraZeneca vaccine is currently considerably cheaper than alternative vaccines (3). But events over the past six months have dented the reputation of the company – and its vaccine. And public trust is waning. 

Communication problems arose in the development stages of the AstraZeneca vaccine. First, there were contradictions in how neurological symptoms in a patient in the vaccine clinical trial were described in the company’s press statements, comments to investors, and internal documents. For example, CNN obtained an internal safety report that detailed how the participant “experienced confirmed transverse myelitis.” The company's CEO, Pascal Soriot, then told investors in a conference call that the trial was stopped because a woman volunteering in the trial had symptoms consistent with transverse myelitis. But later that day, AstraZeneca released a statement saying that “there is no final diagnosis and that there will not be one until more tests are carried out” (4). The incident led to trials being put on hold. Then in November last year, AstraZeneca reported a 90 percent efficacy from their initial trial results, but it became clear that 2741 subjects in the trial had inexplicably received half the intended dosage. Contrary to best practice, the results of full-dose trial and the results of the half-dose trial were combined to give the headline figure (5), leading to bad press and erosion of confidence in the company. 

And this was only the beginning of AstraZeneca’s woes. In January 2021, AstraZeneca found itself in a very public spat with the EU after informing the block that it would be supplying considerably fewer doses of the vaccine than previously agreed. Soriot blamed “yield issues” at one of its manufacturing sites in Europe and cited a “best effort” clause in the contract, but the EU contended the company was contractually obliged to meet the scheduled doses. In the end, both parties published the contract online, with certain parts redacted. The row culminated with the EU publishing its Export Authorization Regulation – giving member states the power to block vaccine exports (6). Italy later exercised the new powers to block a shipment of the vaccine bound for Australia (7). AstraZeneca was also accused of stockpiling vaccines in the EU to export to the UK – and the company’s CDMO partners were caught in the crossfire. Italian inspectors said they had found 29 million vaccine doses at a CDMO factory in Anagni. It was later revealed that 16 million doses were for the EU and the remaining doses were to be supplied to the COVAX program. At the time of the inspection, the vaccines doses had not even been through quality control. AstraZeneca released a statement to clarify the problem, stating: “It is incorrect to describe this as a stockpile. The process of manufacturing vaccines is very complex and time consuming. In particular, vaccine doses must wait for quality control clearance after the filling of vials is completed (8).”

“Quasi-ineffective”

AstraZeneca’s vaccine has also faced criticism about its efficacy. French President Emmanuel Macron said – without evidence – that the vaccine was “quasi-ineffective” in people older than 65, despite the jab having just been approved by the EMA for all adults (9). And a German economic newspaper, Handelsblatt, reported that the vaccine was “apparently hardly effective in seniors.” At the time, German regulators questioned whether there was enough data about how well the vaccine works in those over 65 and advised against approving the vaccine for older adults – although this decision was later reversed (9). In the US, the National Institute of Allergy and Infectious Disease (NIAID) warned that AstraZeneca may have used “outdated” data that provided an “incomplete” picture of its effectiveness. The company then released updated results from its US clinical trial, including more up-to-date data, showing that its vaccine is 76 percent effective (10). However, there are questions about whether this efficacy is maintained against variants (and the same questions are being asked of the other COVID-19 vaccines too).

More recently, the vaccine has faced another PR storm because of blood clots. But AstraZeneca is not alone in this issue; Janssen’s COVID-19 vaccine is facing similar concerns. In March, a number of European countries suspended distribution of the AstraZeneca vaccine and the EMA subsequently determined that unusual blood clots with low blood platelets should be listed as very rare side effects of the vaccine; however, they also noted that the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects (11). Despite this, Denmark has banned the use of the vaccine completely and other EU countries have introduced age limits for the vaccine. Italy, for example, has suggested that it will only use the AstraZeneca vaccine for those over the age of 60 and the UK will only use it in those over the age of 30. At the time of writing, AstraZeneca has yet to release a public statement regarding the blood clotting issue.

Disharmony among different national regulators and laxity on the part of politicians and journalists (whose comments were surely influenced by the politics of the situation) have only added to the confusion caused by AstraZeneca’s communication issues – with regulators, governments and the public. Even before the issues with blood clotting came to light, there were problems with the uptake of the AstraZeneca vaccine in the EU. An investigation by a UK newspaper found that four in five doses delivered to the EU were not being used, as Angea Merkel admitted to an “acceptance problem” (12). It seems inevitable that the recent blood-clotting debacle will further dent the public’s confidence in the vaccine. Indeed, a recent report found that up to 80 percent of people offered the AstraZeneca vaccine in Sicily refused it due to safety fears (13). 

What can the industry learn from the debacle? The fact remains that the AstraZeneca vaccine is the most sought-after vaccine in the world, with over three-billion doses having been purchased worldwide – partly because it can be stored at normal refrigerator temperatures. It is also proven to be safe and effective, and it is already playing a pivotal role in the pandemic, with millions of people across the world already having been vaccinated. Yet, as Moderna expects to make $18 billion in revenue this year from their vaccine and Pfizer/BioNTech $15 billion, AstraZeneca’s share price is down (14). Is AstraZeneca getting the credit it deserves for turning down huge profits and saving healthcare systems billions in the process? 

Once the dust settles, let’s hope that the lesson learned is about the importance of clear communication rather than questioning whether not-for-profit development is worth the hassle.