Sotrovimab 500mg/8ml solution for infusion vials

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

AimSince the first cases of the COVID-19 pandemic, caused by the SARS-CoV-2 virus, described in 2019, numerous drugs have been proposed for the treatment of the disease. However, studies have given contradictory or inconclusive results, making it difficult to determine which treatments are truly effective. The objective was to carry out a systematic review of the literature analyzing the effectiveness (mortality, hospitalization and clinical improvement) of COVID-19 treatments initially proposed and finally authorized in the European Union.MethodsPubMed and other electronic databases were systematically searched for meta-analyses published between January 2020 and December 2022, as well as two additional searches: one of individual clinical studies published until October 2023 and another of those drugs that were considered at the beginning and that were discarded early because the clinical results were unfavorable.ResultsIn the synthesis, 85 meta-analyses and 19 additional clinical studies were included (base case). All medications indicated in the treatment of COVID-19 have favorable efficacy results (mortality, hospitalization rate, clinical improvement) but these results were not confirmed in all studies carried out, being frequently contradictory (confirming or not confirming the impact of treatment on mortality). According to meta-analysis with the largest sample size, the drugs with the greatest evidence of effectiveness in reducing mortality are remdesivir (HR= 0.79; 95% CI 0.73-0.85) and tocilizumab (OR= 0.73; 95% CI 0.56-0.93). Regarding the composite of Covid-19-related hospitalization or death from any cause, the drugs with the greatest evidence of efficacy are remdesivir, nirmatrelvir/ritonavir and sotrovimab (although, currently the effectiveness of monoclonal antibodies against the new variants of the virus has not been demonstrated).ConclusionAccording to this systematic review, the treatments with the greatest evidence of reducing mortality in patients with COVID-19 are remdesivir and tocilizumab.

Abstract licence: CC BY

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

Introduction SARS-CoV-2 virus inflicts a major ongoing medical toll via acute infection with substantial morbid and mortal outcomes, as well as post-acute sequelae. Multiple SARS-CoV-2 RBD-directed mAbs, which emulate native human immunobiology following infection, have been developed, authorized, and demonstrated substantial efficacy for treatment of COVID-19. However, rapid virus evolution challenges traditional development pathways, as non-susceptible variants can emerge faster than development and regulatory review can be completed. Fortunately, mAb antiviral activity across viral variants can be measured via clinical serum virus neutralizing antibody titers that correlate to demonstrated clinical outcomes from historical mAbs and serve as surrogate biomarkers for efficacy. This analytic immunobridging approach is useful for rapid assessment of novel mAb efficacy, especially for mAbs engineered from a clinically established molecular ancestor. Immunobridging is commonly used in vaccine development and supported the Emergency Use Authorization (EUA) of pemivibart, a mAb targeted to the spike protein of SARS-CoV-2 for prevention of COVID-19 in immunocompromised patients. We therefore applied a similar framework to evaluate pemivibart for the treatment of acute COVID-19, aiming to address the urgent unmet needs of immunocompromised patients who remain vulnerable despite vaccination and antiviral therapies, but failed to secure FDA authorization. Methods Three complementary methods were used to evaluate immunobridging of pemivibart against 4 dominant variants (JN.1, KP.3.1.1, XEC, and LP.8.1) for the treatment of COVID-19: 1) strict immunobridging of neutralizing antibody titers of pemivibart to its parent molecule adintrevimab, 2) benchmarking comparison of neutralizing antibody titers of pemivibart to other historical mAbs with prior demonstrated efficacy in the treatment of COVID-19, and 3) dose-response analysis of pemivibart to comparator mAbs based on a published meta-analysis. Results Pemivibart demonstrated strict immunobridging to adintrevimab from 4 to >14 days, depending on variant analyzed. Neutralizing titers of pemivibart across variants were 4-12-fold higher than titers demonstrated for sotrovimab and less than titers for other historical IV-administered mAbs throughout a 14-day analysis period. The dose-response analysis predicted pemivibart to have equivalent efficacy to all other comparator mAbs. Conclusion Following a similar approach to prevention, immunobridging was demonstrated for pemivibart for the treatment of COVID-19 using multiple complementary methods and suggesting substantial antiviral activity that would accelerate and amplify the native human antibody response. This development methodology, which draws on quantitative virology, biological mechanism, and the U.S. regulatory response to our initial approach provides a road map for accelerating novel COVID-19 treatment options in the face of a changing variant landscape. Competing Interest Statement Authors were employees of Invivyd, Inc. (A.H., K.N., I.Y., M.W.) or contractors of Invivyd, Inc. (L.H.) at the time this research was conducted and may hold stock or shares in Invivyd, Inc. Funding Statement This work was supported by Invivyd, Inc. Ethics and Reporting The authors declare that all relevant ethical guidelines have been followed, all necessary IRB and/or ethics committee approvals have been obtained, all necessary patient/participant consent has been obtained and the appropriate institutional forms archived for referenced trials supported by Invivyd, Inc.

Abstract licence: CC BY-ND

BackgroundMultiple SARS-CoV-2 receptor-binding domain-directed monoclonal antibodies (mAbs) have demonstrated substantial efficacy for the treatment of COVID-19. However, rapid virus evolution challenges traditional development pathways, as nonsusceptible variants can outpace development and regulatory review. Fortunately, mAb antiviral activity across variants can be measured via clinical serum virus-neutralizing antibody titers that correlate to clinical outcomes from historical mAbs and serve as surrogate biomarkers for efficacy. Analytic immunobridging facilitates rapid assessment of novel mAb efficacy. Immunobridging supported the Emergency Use Authorization of pemivibart, a mAb targeted to the spike protein of SARS-CoV-2 for the prevention of COVID-19 in certain patients with immune compromise. We applied a similar framework to evaluate pemivibart for the treatment of acute COVID-19.MethodsComplementary methods included the following: (1) strict immunobridging of neutralizing antibody titers of pemivibart to its parent molecule adintrevimab, (2) benchmarking comparison of pemivibart to historical mAbs with demonstrated efficacy in COVID-19 treatment, and (3) dose-response analysis of pemivibart vs comparator mAbs based on a meta-analysis.ResultsPemivibart demonstrated strict immunobridging to adintrevimab from 4 to >14 days across the variants analyzed. Neutralizing titers of pemivibart were 4- to 12-fold higher than titers for sotrovimab and less than titers for other historical intravenously administered mAbs throughout a 14-day analysis period. Dose-response analysis predicted pemivibart to have equivalent efficacy to all comparators.ConclusionsFollowing a similar approach to prevention, immunobridging was demonstrated for pemivibart for the treatment of COVID-19, suggesting substantial antiviral activity. This development methodology provides a roadmap for accelerating novel COVID-19 treatment options amid a changing variant landscape.

Abstract licence: CC BY