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Covid-19: UK will not buy Evusheld owing to “insufficient data” on protection, government says

BMJ 2022; 378 doi: https://doi.org/10.1136/bmj.o2021 (Published 15 August 2022) Cite this as: BMJ 2022;378:o2021

Rapid Response:

Abandoning the Winter 2022 protection for the Immunocompromised - a highly irregular, uncomfortable decision for a vulnerable group that we are likely to regret.

Dear Editor

On the morning of Friday 12th of August, the Department of Health released a statement that it would shelve the Winter 2022 protection plan for the 500,000 immunocompromised patients in the UK.

This decision was made despite all major population-scale UK analyses commissioned by the Department of Health and Social Care and other public bodies continuing to show that whilst the majority of the population are protected from Covid-19, considerable risk exists for immunocompromised patients who are unable to respond to vaccines(1,2,3,4.). Immunocompromised individuals experience excess Covid-19 hospitalisation, intensive care admissions and COVID-19 death relative to the general population(5).

Evusheld is a long-acting monoclonal antibody given as Covid-19 pre-exposure therapy. The PROVENT study showed that Evusheld prevented 8 in 10 breakthrough infections, which led to regulatory approval in the UK in March 2022(6). It is the only drug with this indication and is now in routine clinical use in 32 countries. It resembles a viable alternative for protecting immunocompromised patients from Covid-19. In preparation for the Winter plan, an independent advisory group were asked to identify ten key groups who were likely to benefit from Evusheld(7).

In our National Clinical Expert Group consultation, commissioned by the All Party Parliamentary Group for clinically vulnerable groups, we asked over 125 doctors across 17 specialities and 4 nations to share their views regarding the utility of Evusheld. There was unanimous agreement of the clinical imperative and rationale to deliver the Winter 2022 plan for the immunocompromised to benefit patients, healthcare systems and communities(8).

Despite this, the government have announced that they will not purchase Evusheld as part of this plan due to “insufficient data on the duration of protection offered by Evusheld in relation to the Omicron variant” and “the decision is based on independent clinical advice by Rapid C-19, a multi-agency group”. The Antiviral and Therapeutic Taskforce has referred Evusheld for a prolonged but thorough cost-effectiveness appraisal by NICE. This is the first coronavirus drug to undergo this process prior to commissioning and a report is not expected until April 2023. This leaves immunocompromised individuals without any prophylactic antibody therapies over the winter period.

This decision may have been influenced by concerns regarding the effectiveness of Evusheld against newer omicron variants. Laboratory studies utilising a viral neutralisation assay against omicron subvariants (used as a surrogate marker for human effectiveness) suggest that a higher treatment dose is required to achieve IC50(9). However, neutralisation remains achievable with Evusheld(10,11,12). AstraZeneca has since increased the recommended dose and real-world human studies from France, Israel and the United States continue to show ongoing clinical effectiveness(13,14,15,16,17). Given the initial MHRA approval and international support for Evusheld, the discrepancy in judgement between the UK government and the rest of the world raises legitimate questions.

As immunocompromised patients are at higher risk of severe Covid-19, many have continued to shield, causing significant impact on their quality of life. The decision to strip a critical layer of protection for these individuals and the lack of communication and transparency of the decision-making process has exacerbated concerns and distress in patients.

Grassroot patient campaigns have now been established across every immunocompromised patient speciality group, with universal backing and support from their charities and doctors. These groups have started to publicise views on television and newspapers(18,19,20,21,22,23). We call on decision makers to consider plans to enable our most vulnerable and immunocompromised patients the ability to access prophylactic antibody treatments. For many, the prospect of another winter in isolation will be a tough pill to swallow and the accusation that this patient group has been abandoned by policy makers is difficult to dispute.

References
1 Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA.
2 Kuderer NM, Choueiri TK, Shah DP, et al.. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020; 395:1907–18.
3 Yi SG, Rogers AW, Saharia A, et al.. Early experience with COVID-19 and solid organ transplantation at a US high-volume transplant center. Transplantation. 2020. doi: 10.1097/TP.0000000000003339.
4 Akalin E, Azzi Y, Bartash R, et al.. Covid-19 and kidney transplantation. N Engl J Med. Published online April 2020; 382:2475–7. doi: 10.1056/NEJMc2011117.
5 Turtle, L. et al. Outcome of COVID-19 in hospitalised immunocompromised patients: an analysis of the WHO ISARIC CCP-UK prospective cohort study. medRxiv 2022.08.08.22278576; https://doi.org/10.1101/2022.08.08.22278576
6 Levin MJ, Ustianowski A, De Wit S, Launay O, Avila M, Templeton A, Yuan Y, Seegobin S, Ellery A, Levinson DJ, Ambery P, Arends RH, Beavon R, Dey K, Garbes P, Kelly EJ, Koh GCKW, Near KA, Padilla KW, Psachoulia K, Sharbaugh A, Streicher K, Pangalos MN, Esser MT; PROVENT Study Group. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022 Jun 9;386(23):2188-2200. doi: 10.1056/NEJMoa2116620. Epub 2022 Apr 20. PMID: 35443106; PMCID: PMC9069994.
7 https://www.gov.uk/government/publications/higher-risk-patients-eligible...)
8 https://appg-vulnerablegroups.org/news/post/leading-charities-and-clinic...
9 National Institutes of Health. National Center for Advancing Translational Sciences Open Data Portal. SARS-CoV-2 Variants & Therapeutics. AZD7442 (AZD8895 and AZD1061; mAbs for SARS-CoV-2) Omicron Antiviral Resistance Information. Available at: https://opendata.ncats.nih.gov/variant/datasets?id=160
10 VanBlargan, L.A., Errico, J.M., Halfmann, P.J. et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med 28, 490–495 (2022). https://doi.org/10.1038/s41591-021-01678-y
11 Case JB, Mackin S, Errico JM, Chong Z, Madden EA, Whitener B, Guarino B, Schmid MA, Rosenthal K, Ren K, Dang HV, Snell G, Jung A, Droit L, Handley SA, Halfmann PJ, Kawaoka Y, Crowe JE Jr, Fremont DH, Virgin HW, Loo YM, Esser MT, Purcell LA, Corti D, Diamond MS. Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains. Nat Commun. 2022 Jul 2;13(1):3824.
12 Bruel, T., Hadjadj, J., Maes, P. et al. Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies. Nat Med 28, 1297–1302 (2022). https://doi.org/10.1038/s41591-022-01792-5
13 Young-Xu et al. Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data. Preprint. MedRxiv. doi: https://doi.org/10.1101/2022.05.28.22275716
14 Al Jurdi A, Morena L, Cote M, Bethea E, Azzi J, Riella LV. Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave. Am J Transplant. 2022 Jun 21. doi: 10.1111/ajt.17128. Epub ahead of print. PMID: 35727916.
15 Bertrand D., Laurent C., Lemée V., et al. Efficacy of anti-SARS-CoV-2 monoclonal antibody prophylaxis and vaccination on the Omicron variant of COVID-19 in kidney transplant recipients. Kidney Int. 2022;102:440–442.
16 Kaminski H, Gigan M, Vermorel A, Charrier M, Guirle L, Jambon F, Lacapère A, Ménard C, Moreau K, Neau-Cransac M, Novion M, Pribat F, Taton B, Borde S, Burguet L, Martinez C, Jasiek M, D'Halluin P, Lafon ME, Merville P, Couzi L. COVID-19 morbidity decreases with tixagevimab-cilgavimab preexposure prophylaxis in kidney transplant recipient nonresponders/low-vaccine responders. Kidney Int. 2022 Jul 20:S0085-2538(22)00550-6.
17 Jennifer Kertes, Shirley Shapiro Ben David, Noya Engel-Zohar, Keren Rosen, Beatriz Hemo, Avner Kantor, Limor Adler, Naama Shamir Stein, Miri Mizrahi Reuveni, Arnon Shahar, Association between AZD7442 (tixagevimab-cilgavimab) administration and SARS-CoV-2 infection, hospitalization and mortality, Clinical Infectious Diseases, 2022;, ciac625, https://doi.org/10.1093/cid/ciac625
18 https://inews.co.uk/opinion/the-governments-decision-not-to-provide-evus...
19 https://www.theguardian.com/world/2022/aug/12/uk-decision-not-to-buy-cov...
20 https://www.dailymail.co.uk/health/article-11108725/Covid-19-Outrage-NHS...
21 https://www.dailymail.co.uk/health/article-11064929/Doctors-demand-NHS-f...
22 https://www.dailymail.co.uk/news/article-11109393/Ministers-accused-fail...
23 https://bloodcancer.org.uk/news/whats-the-latest-on-evusheld/

Competing interests: No competing interests

19 August 2022
Lennard YW Lee
Academic Medical Oncologist
Keeley Bernhardt, Professor Antonio Pagliuca, Professor Alex Richter
University of Oxford, King's College London, University of Birmingham
lennard.lee@nhs.net