No vaccination against politics

Doing drugs may be a lifestyle choice for many people but for pharmaceutical companies there is little choice – if they are not in the drugs business, they are not in business at all. But the drugs business is not quite like any other. Although pharma companies are similar to other private sector companies in trying to make a profit from their work, they are also very different in that much of their input yields very little return. The industry also runs into a host of ethical problems. One of the trickiest issues is whether it is right that they should generate abnormal profit at the expense of the sick? Yet over the last 12 months we have been very glad of their efforts as the industry has produced a number of vaccines against Covid-19. But even these heroic efforts have not prevented companies from being drawn into major controversies as the politics of vaccination starts to kick in.

Four vaccines have been authorised for use in the EU: Comirnaty (aka the Pfizer-BioNTech vaccine); the Moderna vaccine; the Janssen vaccine and Vaxzevria (known until yesterday as the AstraZeneca vaccine). It is the latter of these which has fallen foul of vaccine politics to a far greater degree than the others.

The (drug) trials and tribulations of AstraZeneca

Since the start Vaxzevria (known hereafter as the AZ vaccine) has suffered from the perception that it is less effective than its competitors. Back in November Pfizer was the first producer to announce the results of its clinical trials, suggesting that its vaccine had an efficacy rate around 94% whilst Moderna made a similar claim. Initial trials of the AZ vaccine suggested an efficacy rate of just 62%. But AZ subsequently announced that the efficacy rate amongst participants who received a lower amount of the vaccine in the first dose and then the full amount in the second dose rose to 90%. For the layperson, the suspicion was sown that AZ had somehow tried to “fix” its results to bring them into line with those from other producers. The waters were further muddied when it subsequently came to light that the low dose trial did not include anyone over the age of 55, raising concerns that the higher efficacy was merely a by-product of excluding an age group that is particularly vulnerable to Covid. This led to a situation whereby many EU countries initially refused to licence the AZ vaccine for older age groups. Bizarrely, Germany has now licensed it only for the over-60s. 

Although the EU and UK did grant a form of authorisation to the AZ vaccine, it had until recently still not received a licence for distribution in the US which is critical to global acceptance. The US Food and Drug Administration (FDA) had asked AZ to conduct a larger trial in order to get clearer data than they obtained in their first rounds of testing. In late March, AZ thus released data showing that its vaccine is 79% percent effective at preventing symptomatic disease. But in an unprecedented move the National Institute of Allergy and Infectious Diseases (NIAID) released a letter stating that the AZ results were based on outdated data. Within 48 hours AZ released an updated set of results stating that the vaccine has 76% percent efficacy in reducing symptomatic Covid-19 overall, and 85% in people 65 years old and older.  

To make matters worse a number of countries suspended the use of the AZ vaccine altogether on reports that a number of patients suffered blood clots (thromboembolic events) as a reaction. Although the European Medicines Agency subsequently stated that “the number of thromboembolic events in vaccinated people is no higher than the number seen in the general population” this is just another example of the reputational damage which has been inflicted on the AZ vaccine.  

Was it worth it?

AstraZeneca’s management can be forgiven for wondering whether their efforts to develop a vaccine which is significantly cheaper than its competitors and which will be sold at cost to developing countries were worthwhile. There is considerable evidence that people in many countries much prefer to be injected with the Pfizer vaccine rather than the AZ version with Germans and Canadians showing a clear preference for the former. As a result AstraZeneca’s share price has underperformed that of Pfizer in recent weeks.

Under normal circumstances AZ’s efforts to deliver a vaccine to combat a new disease at such a rapid pace and at a low cost would be lauded as a miracle of science. Yet it has dominated the headlines for all the wrong reasons. In some ways it is hard to refute the claim made by Anthony Fauci, the US President’s chief medical advisor, that AZ has made “unforced errors” in its handling of the process. Communication of the drug trial results has been very confusing and the issues with NIAID could perhaps have better been handled had both sides liaised better before announcing the results.

Some of the issues may also stem in part from the fact that AZ does not have a lot of experience in vaccine production. According to the experts, the productivity of identical plants can differ for no apparent reason with the result that there can be considerable variation in quality across batches. The international supply chain dimension further adds to the complexities of vaccine production. As a consequence AZ may have underestimated its ability to produce the volume of vaccine which it promised. This became a convenient stick with which to beat the company, thus diverting attention away from the failures of the vaccine rollout programme in parts of the EU.

For all this, the work of AstraZeneca deserves a lot more praise than it has so far attracted from large parts of the international press. The vaccine is far easier to store than those developed by Pfizer and Moderna, making it much more useful in those countries which may not have the capacity to store it at the low temperatures which they require. Moreover it is being used and saving lives which is more than can be said for all those companies which are engaged in vaccine research and whose products have yet to see the light of day – not because they are not good at their work but because vaccine development is a difficult process.

AstraZeneca has unfortunately fallen victim to vaccine politics

Indeed, not all the blame attributed to AZ is of its own making. Whilst it is true that the EU countries have exported the AZ vaccine to the UK whereas there has been no flow in the other direction, this is partly to do with the details of the respective contracts drawn up between AstraZeneca and the UK/EU. This article, quoting a Belgian contract law specialist, explains why the UK’s legal position with regard to supply is stronger than that of the EU. Interested readers are referred to the article for the detail but the key points are:

1. The UK contract is written in English law which is quite specific about assessing whether both parties delivered the goods. By contrast the EU contract is written in Belgian law, which puts a lot of emphasis on the concept of good faith in determining whether both parties tried their best to deliver the goods; 
2. The UK contract made it clear that the whole supply chain process was taken into account whereas the EU focused only on delivery;
3. The UK contract has stricter enforcement penalties than that drawn up by the Commission which left it somewhat toothless.       
   

The influential MEP Guy Verhofstadt is quoted as saying “since the outcome of this particular contract has led to an enormous amount of public distrust, both the Commission and AstraZeneca have a lot of explaining to do.” But it rather looks as if it is the former, rather than the latter, where the problems lie since the contract drawn up by the Commission appears to be less watertight than the one AZ signed with the UK. That said, AZ has under-delivered and if it has learned anything from this debacle, it is that it needs to manage expectations more effectively.  

But we should not rush to judgement. Only once the recent teething troubles have been sorted can we can really assess whether the EU’s vaccine rollout has really been so bad (it is likely to catch up quickly) and whether AZ has lived up to its promise to deliver a low-cost vaccine that has saved the world.