Cilgavimab 150mg/1.5ml solution for injection vials

Immunocompromised patients, such as those with a haematological malignancy, are at higher risk of SARS-CoV-2 infection, severe outcomes and mortality. Tixagevimab/cilgavimab is a monoclonal antibody combination which binds to the SARS-CoV-2 spike protein. The PROVENT phase III clinical trial reported that tixagevimab/cilgavimab prophylaxis significantly reduced the risk of COVID-19 infection in immunocompromised participants. However, the trial was conducted before the Omicron variant became prevalent. This systematic review and meta-analysis provide an up-to-date summary of the real-world effectiveness of tixagevimab/cilgavimab in immunocompromised patients, including patients with haematological malignancies. Clinical studies from 1 January 2021 to 1 October 2022, which reported breakthrough COVID-19 infections after tixagevimab/cilgavimab, were included. COVID-19-related hospitalisations, intensive care admissions and mortality were also assessed. A meta-analysis was performed to ascertain overall clinical effectiveness. Eighteen studies, with 25 345 immunocompromised participants, including 5438 patients with haematological pathologies, were included in the review. The overall clinical effectiveness of tixagevimab/cilgavimab against COVID-19 breakthrough infection, hospitalisation, intensive care admission and COVID-19-specific mortality was 40.54%, 66.19%, 82.13% and 92.39%, respectively. This review highlights the clinical effectiveness of tixagevimab/cilgavimab at reducing COVID-19 infection and severe outcomes for immunosuppressed individuals, including patients with a haematological malignancy, during the Omicron-predominant era. Real-world studies are important to provide ongoing certainty of the clinical benefit for immunocompromised patients against new SARS-CoV-2 variants.

Abstract licence: CC BY-NC-ND 4.0

BackgroundMonoclonal antibodies (mAbs) and antiviral drugs have emerged as additional tools for treatment of COVID-19.AimWe aimed to review data on susceptibility of 14 SARS-CoV-2 variants to mAbs and antiviral drugs authorised in the European Union/European Economic Area (EU/EEA) countries.MethodsWe constructed a literature review compiling 298 publications from four databases: PubMed, Science Direct, LitCovid and BioRxiv/MedRxiv preprint servers. We included publications on nirmatrelvir and ritonavir, remdesivir and tixagevimab and cilgavimab, regdanvimab, casirivimab and imdevimab, and sotrovimab approved by the European Medicines Agency (EMA) by 1 October 2024.ResultsThe mutations identified in the open reading frame (ORF)1ab, specifically nsp5:H172Y, nsp5:H172Y and Q189E, nsp5:L50F and E166V and nsp5:L50F, E166A and L167V, led to a decrease in susceptibility to nirmatrelvir and ritonavir, ranging from moderate (25-99) to high reductions (> 100). Casirivimab and imdevimab exhibited highly reduced neutralisation capacity across all Omicron sub-lineages. Sub-lineages BA.1, BA.2 and BA.5 had decreased susceptibility to regdanvimab, while sotrovimab showed decreased efficacy for BA.2, BA.4, BQ.1.1 and BA.2.86. Tixagevimab and cilgavimab exhibited highly reduced neutralisation activity against BQ.1, BQ.1.1, XBB, XBB.1.5 and BA.2.86 sub-lineages.ConclusionsThe emergence of new variants, some with altered antigenic characteristics, may lead to resistance against mAbs and/or antiviral drugs and evasion of immunity induced naturally or by vaccination. This summary of mutations, combination of mutations and SARS-CoV-2 variants linked to reduced susceptibility to mAbs and antiviral drugs, should aid the selection of appropriate treatment strategies and/or phasing out therapies that have lost their effectiveness.

Abstract licence: CC BY

BackgroundKidney transplant recipients (KTRs) are most vulnerable to infection in the first year after transplantation. Tixagevimab and cilgavimab are neutralizing monoclonal antibodies directed against different epitopes of the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein. The purpose of this study is to report experience with tixagevimab/cilgavimab administered to KTRs who were within 1 year of transplantation.AimTo describe outcomes of KTRs who received tixagevimab/cilgavimab early posttransplant to prevent coronavirus disease 2019 (COVID-19).MethodsThis is a single-center retrospective cohort study of adult KTRs who underwent kidney transplantation from January 1, 2022 to September 30, 2022 and received tixagevimab/cilgavimab 300 mg/300 mg for prevention of COVID-19. Outcomes of interest were adverse events associated with tixagevimab/cilgavimab, COVID-19 breakthrough infection and COVID-19-associated hospitalization and complications. We also conducted a systematic review of the literature for the use of tixagevimab/cilgavimab as pre-exposure prophylaxis for COVID-19 in solid organ transplant recipients (SOTRs) from inception to December 31, 2023.ResultsThere were 104 patients included with median age of 50 years (range 21-72 years). Omicron strain of the COVID-19 virus was the predominantly circulating variant at the time of current study. Patients testing positive for COVID-19 were given tixagevimab/cilgavimab for prophylaxis of complications during the median of 3 days (range 0-201 days) after kidney transplant, of whom 97 (93.3%) received the antibodies prior to discharge. No discernable adverse effects attributable to the medication were observed during the time they received prophylaxis. The efficacy of the drug assessed through the absence of breakthrough infections were observed in 91 patients. 13 (12.5%) patients developed COVID-19 breakthrough infections during an overall median follow-up period of 125 days (range 10-257 days) after tixagevimab/cilgavimab. These infections were observed at median 105 days (range 6-211 days) after receiving the prophylactic medication. 5 (4.8%) of overall patients required hospitalization and there were no reported deaths in the cohort. Findings of the systematic review were consistent with our findings wherein tixagevimab/cilgavimab was well tolerated by SOTRs.ConclusionTixagevimab/cilgavimab has a favorable safety profile when administered in newly transplanted kidney recipients. Although breakthrough infections were not uncommon, there was a low rate of hospitalization and no deaths. This study highlights the need to examine the efficacy of novel monoclonal antibodies administered for COVID-19 prophylaxis in newly transplanted recipients.

Abstract licence: CC BY-NC

BackgroundHigh-risk populations, including transplant recipients, are at increased risk of severe Coronavirus disease 2019 (COVID-19) outcomes. Certain treatments and pre-exposure prophylaxis (PrEP) have been approved to reduce the risk of severe illness. However, data on the cost effectiveness of currently approved COVID-19 therapeutics and preventative treatments are limited for those at high-risk of severe disease.ObjectiveThe aim of this study was to systematically review the cost effectiveness of COVID-19 treatments and PrEP in high-risk, immunocompromised, and transplant populations.MethodsElectronic databases were searched from inception to September 2025 for studies comparing costs and effectiveness of monoclonal antibodies PrEP or COVID-19 therapeutics in high-risk, immunocompromised or transplant populations. Two reviewers independently screened studies, extracted data, and critically appraised them using the Joanna Briggs Institute checklist for economic evaluations. Cost data are presented in 2025 US dollars.ResultsOf 8905 studies identified, 60 met inclusion criteria, with seven focused on or including transplant populations. Most studies were cost-utility analyses published between 2020 and 2025. Nirmatrelvir-ritonavir, tixagevimab-cilgavimab, casirivimab-imdevimab, sotrovimab, remdesivir, molnupiravir, and fluvoxamine were compared with no prophylaxis or standard of care. Among transplant populations, the incremental cost-effectiveness ratio (ICER) for tixagevimab-cilgavimab PrEP following vaccination was US$76,024 per quality-adjusted life year (QALY), while ICERs for COVID-19 therapeutics ranged from US$440 to US$126,676 per QALY.ConclusionCost effectiveness varied widely across studies due to differences in variant periods, population risk profiles, model assumptions, and healthcare systems. Future research should integrate variant-specific effectiveness, real-world vaccine responsiveness, long-term COVID-19 outcomes, and adverse events to better inform resource allocation for transplant and other high-risk populations.

Abstract licence: CC BY-NC