AstraZeneca’s Evusheld (tixagevimab co-packaged with cilgavimab) has been authorised by the Medicines and Healthcare products Regulatory Agency (MHRA) and is the first antibody combination for pre-exposure prophylaxis (PrEP) against Covid-19 licensed in Great Britain.
The use of this medicine is for adults who are not currently infected with (or know exposure to) the Covid-19 virus and are unlikely to mount an adequate response to Covid-19 vaccination – including those for whom vaccination is not recommended.1
The decision to grant approval for this treatment was endorsed by the UK government’s independent expert scientific advisory body, the Commission on Human Medicines, after carefully reviewing the evidence.
The evidence
The primary data from the ongoing PROVENT Phase III trial (which met its primary endpoint) showed a statistically significant reduction in the risk of developing symptomatic Covid-19 with AZD7442 compared to placebo. The trial has shown protection from the virus continuing for at least six months. The antibody was tolerated and follow-up is needed to establish the full duration of protection.1
Based on the primary analysis of 5,172 participants (AZD7442 n = 3,441 and saline placebo n = 1,731), the antibody combination demonstrated a 77% relative risk reduction (RRR) in incidence of symptomatic Covid-19 [95% Confidence Interval (CI) 46-90; p <0.001; 8/3,441 (0.2%) AZD7442 and 17/1,731 (1.0%) placebo], and 0.8% Absolute Risk Reduction (ARR) compared to placebo, with median follow-up time post-administration of 83 days.1,4
In a subsequent analysis, the antibody combination demonstrated an 83% RRR in the incidence of symptomatic Covid-19 [95% CI: 66-91; 11/3,441 (0.3%) AZD7442 and 31/1,731 (1.8%) placebo] and 1.5% ARR compared to placebo, after a median 6.5-month follow-up.1
No hospitalisation or deaths were seen in the treatment arm. In the placebo arm, there were five cases of severe Covid-19 and two Covid-19 related deaths. Adverse events were reported in 35% (1,221/3,461) of participants receiving AZD7442 and 34% (593/1,736) receiving placebo, with the vast majority being mild to moderate in nature. The most frequently reported adverse reaction in the pooled analysis was injection site reaction.4,5
Context
About 500,000 people in the UK are immunocompromised and may benefit from this medicine for pre-exposure prophylaxis of Covid-19.2 Nearly 40% of people with immunocompromised or immunosuppressed conditions mount a low or undetectable immune response after vaccination and approximately 11% fail to generate any antibodies.3 This includes people with blood cancers, those taking immunosuppressive drugs after an organ transplant or for conditions including multiple sclerosis and rheumatoid arthritis.3
Official comments
Tom Keith Roach, President of AstraZeneca UK, said: “Evusheld fills an urgent gap in the UK’s fight against Covid-19, providing protection for people for whom vaccination may not be effective and who are often amongst the most clinically vulnerable in society. We hope to see this critical medicine made available to UK patients as quickly as possible, in line with other countries.”
Hugh Montgomery, Professor of Intensive Care Medicine at University College London, said: “This announcement is really good news. Sensible public health actions with vaccination are the mainstay of protection for most individuals in the UK. However, for a considerable number in society with existing health problems, protection against the virus through vaccination is limited. Availability of this antibody medicine now offers an increased likelihood of pre-exposure protection, and all from a single, effective immunisation that can last for months.”
Dr June Raine, MHRA Chief Executive, said: “After a careful review of the data, I am pleased to confirm that we have authorised another medicine to help protect against the effects of Covid-19. Evusheld is a “pre-exposure prophylaxis” treatment, meaning it is taken to prevent Covid-19 before the risk of acquiring infection. One dose has been found to provide long-lasting protection against this disease for up to 6 months.
“While the Covid-19 vaccines continue to be the first-line defence against Covid-19, we know that some people may not respond adequately to these vaccines and for a small number of individuals Covid-19 vaccines may not be recommended for other reasons, such as a previous allergic reaction to one of the vaccine ingredients. For these people, Evusheld could provide effective protection against Covid-19.”
Professor Munir Pirmohamed, Chair of the Commission on Human Medicines, said: “The Commission on Human Medicines and its Covid-19 Therapeutics Expert Working Group has independently reviewed the data and endorses the MHRA’s regulatory approval of Evusheld. We have carefully reviewed data on the medicine’s safety, quality and effectiveness and are satisfied it meets the expected standards. The recommended dosage is 300 mg of Evusheld but a higher dose of 600 mg may be more appropriate for some Covid-19 variants. All this is outlined in the Summary of Product Characteristics. Pre-exposure prophylaxis with Evusheld is not a substitute for vaccination in individuals for whom Covid-19 vaccination is recommended.”
References
- Summary of Product Charecterics, Evusheld (on file): To be available at www.medicines.org.uk/emc
- Blood Cancer UK https://bloodcancer.org.uk/news/were-calling-on-the-government-to-postpone-lifting-restrictions-on-june-21/ [Last accessed: March 2022].
- NIHR, OCTAVE TRIAL https://www.nihr.ac.uk/news/octave-trial-initial-data-on-vaccine-responses-in-patients-with-impaired-immune-systems/28529 [Last accessed: March 2022]
- FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELD™ (tixagevimab co-packaged with cilgavimab) https://www.fda.gov/media/154701/download [Last accessed: March 2022]
- Levin et al. LB5. PROVENT: Phase 3 Study of Efficacy and Safety of AZD7442 (Tixagevimab/Cilgavimab) for Pre-exposure Prophylaxis of COVID-19 in Adults. ID Week. 2021
