Controversy for AstraZeneca as they release positive US trial data for the COVID-19 vaccine, AZD1222

AstraZeneca's COVID-19 vaccine is safe in over 65 years olds

Date: 23rd March 2021

AstraZeneca have announced the interim results of their US Phase III trial of their COVID-19 vaccine, AZD1222.  The trial, called D8110C00001, showed the vaccine was 79% effective at preventing symptomatic COVID-19, and had 100% efficacy against severe or critical disease and hospitalisation.  The vaccine was 80% efficacious in the 65 years and over age group, and showed no increased risk of thrombosis.

AZD1222, has been granted a conditional marketing authorisation or emergency use in more than 70 countries across the globe, and with the World Health Organisation (WHO) also granting Emergency Use Listing it is included in COVAX, COVID-19 Vaccines Global Access, a global initiative aimed at equitable access to COVID-19 vaccines – making it available to 142 countries through this facility.

AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech, and is made from a replication-deficient chimpanzee viral vector – adenovirus – which contains the genetic code to the SARS-CoV-2 viral spike protein.

One huge advantage of this type of vaccine is that it is stable at fridge temperature (2-8oC).  Whilst, this means that transportation is done in a refrigerated van or cool box, this method of transport and subsequent storage in a domestic fridge is already how most vaccine are distributed, meaning it can be easily administered in existing healthcare systems using current infrastructures.  As such, this vaccine has the potential to be a critical strategic tool in the fight to stop the current pandemic, and will play a crucial role in easing strict lockdown rules that many countries are currently facing.

However, current questions surrounding its use in participants 65 years and over, and a possible link to rare blood clots, has caused a halt in vaccine programmes in several countries, many of whom are now experiencing new waves of infections, despite the WHO urging its continued rollout.

Phase III clinical trial

The large-scale D8110C00001 trial involved 32,449 participants across 88 trial centres in the US, Peru and Chile, and accrued 141 symptomatic cases of COVID-19. Overall, the data demonstrated statistically significant vaccine efficacy of 79% at preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and hospitalisation.

Vaccine efficacy was consistent across ethnicity and age – 79% were white/Caucasian, 8% black/African American, 4% native American and 4% Asian, and 22% of participants were Hispanic.  In participants aged 65 years and over the vaccine was 80% efficacious – ~20% of the particpants fell into this age group, with around 60% having co-morbidities associated with an increased risk for progression of severe COVID-19, such as diabetes, severe obesity or cardiac disease.

The vaccine data was examined by the independent data safety monitoring board (DSMB) and an independent neurologist, who conducted a specific review of thrombotic events and cerebral venous sinus thrombosis (CVST). There was found to be no increased risk of thrombosis or related events amongst the 21,583 participants who had received at least one dose of AZD1222.   The vaccine was overall well tolerated and there were no safety concerns identified related to the vaccine.

Conclusions and future applications

This is an important milestone for AZD1222, its safe use in older participants, and no increased risk of thrombosis will add confidence for its more widespread use. As it is not currently approved for use in the US, AstraZeneca are preparing to submit the finding to the US Food and Drug Administration (FDA) for Emergency Use Authorisation (EUA).

AZD1222, it given in two doses, here a month apart, however, recent data provided evidence that a 12-week prime-boost interval is an optimal approach for the vaccine roll out.  This extended dose interval, and ease of storage will play an important role in protecting millions of people worldwide against this lethal virus.

If approved for use in the US, how its production and supply chains are managed will be an interesting matter.  With production issues already creating tensions between the UK government and European commission, vaccine control and export is becoming a battlefield.

Furthermore, a statement released late yesterday by the National Institute of Allergy and Infectious Diseases (NIAID),US, announced that they had be notified by the DSMB that they were concerned by information released by AstraZeneca on initial data from its COVID-19 vaccine clinical trial. The DSMB expressed concerns that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.  This is yet another unwelcome hurdle for AstraZeneca, who quickly responded that they would immediately engage with the DSMB to share the primary analysis with the most up to date efficacy data, and would issue the results within 48 hours.


For more information please see the Phase III press release from AstraZeneca