Please Sir, may I have some...Evusheld

Pat is one of our many solid organ transplant patients whose life depends on ongoing immunosuppression. An unfortunate side effect of this treatment can be failure to generate antibodies after vaccination, data shows that around 1 in 10 immunocompromised patients developed no antibodies to covid vaccination and 4 in 10 only a very weak response, leaving them at high risk. 

 While the new antiviral and monoclonal antibody therapies are reported highly effective and very welcome, they may also have significant interactions with some immunosuppressants meaning that for Pat, this may be problematic. Pre- rather than post-exposure prophylaxis would be extremely welcome.

Luckily for Pat, in March 2022, the MHRA granted authorisation of Evusheld in the UK for pre-exposure prophylaxis to prevent COVID-19. This is not a substitute for vaccination, instead, Evusheld is for patients who are “unlikely to mount an immune response from vaccination or in patients where vaccination is not recommended.”

Evusheld is a combination of two long-acting monoclonal antibodies [tixagevimab and cilgavimab] administered via intramuscular injections. The monoclonal antibodies mimic and enhance the immune systems response to COVID-19 and work with almost immediate effect by binding to the SARS-CoV-2 spike protein, preventing the virus from attaching to and from entering cells. 

The main evidence for Evusheld came from the PROVENT trial where 75% of patients had comorbidities putting them at high risk of developing severe COVID-19. They conclude the data supports the use of Evusheld for the prevention of symptomatic and severe COVID-19. They found a relative risk reduction in developing symptomatic COVID-19 with Evusheld compared to placebo of 77% at the primary analysis, and 83% at the six-month analysis, as antibody levels were found to be elevated for 6 months after administration of Evusheld.

In the United States, one of the many countries who have already procured and rolled out Evusheld, the FDA recommended an increase in the Evusheld dose from 300mg to 600mg due to the Omicron subvariants. Recent data from Washington University has shown Evusheld neutralised the BA.2 Omicron subvariant and the following pre-print paper concluded Evusheld is associated with a lower risk of breakthrough SARS-CoV-2 infection, hospitalisation and death from COVID-19 in vaccinated transplant recipients during the Omicron wave.  

Pat asks the million-dollar question, when can I have Evusheld? This decision currently lies with the government who have requested the Department’s Antivirals and Therapeutics Taskforce to evaluate the use of pre-exposure prophylaxis and how this could be deployed in the UK, let’s hope they make the right decision…