Xevudy (sotrovimab) / GSK, National Institutes of Health, Vir Biotech, National Institute of Allergy and Infectious Diseases, Xencor - LARVOL DELTA

Complex intra-host SARS-CoV-2 evolution following monoclonal antibody pre-exposure prophylaxis (IMMUNOLOGY 2026) - "Fixation of E340D abolished the surrogate defence provided by sotrovimab, eliminating neutralizing activity and exerting a positive epistatic effect on emerging mutations."

Hematological Malignancies • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The European Commission withdrew the marketing authorisation for Xevudy (sotrovimab) in the European Union (EU). (European Medicines Agency) - "The withdrawal was at the request of the marketing authorisation holder, GlaxoSmithKline Trading Services Limited, which notified the European Commission of its decision to permanently discontinue the marketing of the product for commercial reasons....The marketing authorisation was initially valid for a 5-year period."

European regulatory • Novel Coronavirus Disease

Outpatient Treatment of Confirmed COVID-19 in Symptomatic Adults: Living, Rapid Practice Points From the American College of Physicians (Version 3). (PubMed, Ann Intern Med) - "Consider nirmatrelvir-ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. Consider molnupiravir to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease...Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. The PHMSC is retiring this topic from living status considering that this update and previous surveillance have not yielded important changes to the practice points."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Value of Emerging and Existing Pre-prophylaxis and Therapeutic Options for COVID-19 in Transplant Recipients: A Systematic Review of Economic Evaluations. (PubMed, Pharmacoecon Open) - "Cost 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."

HEOR • Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Transplantation

AGILE (Early Phase Platform Trial for COVID-19) (clinicaltrials.gov) - P1/2 | N=600 | Recruiting | Sponsor: University of Liverpool | Trial completion date: Oct 2026 ➔ Jul 2026 | Trial primary completion date: Oct 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Viral clearance and escape during therapy of COVID-19 outpatients: A prospective cohort study. (PubMed, iScience) - "The emergence of mutations within Spike was observed in 21.9% of patients, all being immunocompromised treated by Sotrovimab or Tixagevimab/Cilgavimab after Omicron emergence, and was independently associated with higher viral load and serum neutralization at day 7. Our data show that suboptimal neutralizing antibodies should be avoided in immunocompromised individuals, given the risk of emergence of viral escape mutations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Clinical outcomes of sotrovimab in seronegative patients with severe COVID-19: A multicenter retrospective study. (PubMed, Medicine (Baltimore)) - "The high mortality in this cohort underscores the extreme vulnerability of severely immunocompromised patients with COVID-19. These findings support further research into early and prolonged antiviral strategies, potentially combining agents, given the limitations of sotrovimab in the advanced disease stages."

Clinical data • Journal • Observational data • Retrospective data • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Organ Transplantation • Transplantation

TURN-COVID Biobank: The Dutch Cohort Study for the Evaluation of the Use of Neutralizing Monoclonal Antibodies and Other Antiviral Agents Against SARS-CoV-2 (clinicaltrials.gov) - P=N/A | N=1178 | Completed | Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Sep 2025 | Trial primary completion date: Jun 2024 ➔ Sep 2025

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Antibody escape of SARS-CoV-2 variants of concern on receptor-binding domain: A computational approach. (PubMed, J Theor Biol) - "Etesevimab exhibited strong binding with Delta but displayed a weaker connection with Omicron. Therefore, Sotrovimab and Etesevimab remain promising candidates for in vivo and in vivo testing against SARS-CoV-2 variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The Impact of Cognate Antigen Binding on the FcRn-mediated Transcytosis and Recycling of Monoclonal Antibodies. (PubMed, AAPS J) - "This study investigates how cognate antigen binding influences FcRn-mediated transport of two SARS-CoV-2-specific (SCoV-2) monoclonal antibodies: Sotrovimab, an Fc-engineered antibody with enhanced FcRn affinity, and B38, a non-engineered comparator...These data suggest that cognate antigen binding and interaction of immune complexes (ICs) with FcRn, play a major role in influencing transcytosis and recycling of mAb. These findings emphasize the complex interplay between antigen binding and FcRn function, with implications for antibody dosing strategies during infection to optimize tissue distribution and efficacy."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety, Tolerability and Pharmacokinetics of a High-Dose, Rapid-Infusion Monoclonal Antibody: Phase I Results for Intravenous Sotrovimab 3000 mg. (PubMed, Drugs R D) - P1 | "Intravenous sotrovimab 3000 mg, administered over 60 min, was generally well tolerated by healthy volunteers, with a low incidence of adverse events and adverse events of special interest, no documented serious adverse events and no adverse events leading to discontinuation. Pharmacokinetic results were in line with expectations for a 3000-mg dose, assuming linear dose-proportional pharmacokinetics."

Journal • P1 data • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety, Tolerability, Pharmacokinetics, and Viral Pharmacodynamics of the Monoclonal Antibody Sotrovimab Administered via Intramuscular Injection in Participants with Early, Mild-to-Moderate COVID-19: A Randomized Clinical Trial. (PubMed, Drugs R D) - P2 | "Both sotrovimab IM doses were equivalent to 500 mg IV with respect to SARS-CoV-2 VL change. IM administration was safe and well tolerated. The validity of VL as a biomarker for COVID-19 progression warrants further study."

Clinical • Journal • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A cocktail of SARS-CoV-2 spike stem helix domain and receptor binding domain human monoclonal antibodies prevent the emerge of viral escape mutants. (PubMed, bioRxiv) - "The clinical efficacy of early SARS-CoV-2 NAbs has been challenged by the emergence of escape viral variants, highlighting an urgent need to anticipate resistance. Using a luminescent attenuated SARS-CoV-2 platform, we profiled resistant mutations against two broadly protective SARS-CoV-2 NAbs. Passage of Δ3a7b-Nluc in the presence of a NAb targeting the RBD S1 domain (1301B7) readily selected for an ARM, whereas passage in the presence of an SH S2 domain NAb (1249A8) did not. Notably, a cocktail of 1301B7 and 1249A8 created a high barrier of selecting SARS-CoV-2 ARM, preventing the emergence of resistant variants. We identified an S371F mutation in the S1 RBD of ARM-B7 that confers resistance to 1301B7 and other S1 RBD-targeting NAbs. These results highlight the importance of combination therapies targeting both variable RBD S1 and conserved SH S2 domain for the efficient treatment of SARS-CoV-2 and to prevent the emerge of NAb-induced escape mutations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Epic: A Second Interim Analysis of the Non-Interventional, Observational Multi-Centre Cohort Study of Patients with Chronic Lymphocytic Leukaemia Treated with First-Line Acalabrutinib through the UK Early Access Programme (ASH 2023) - P | "Sotrovimab was the most common treatment received for COVID-19 (20% of patients, n=8/40). This IA reports 12 and 24-month real-world acalabrutinib continuation rates of 81. 0% (95% CI, 73. 7%-89."

Clinical • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Nephrology • Oncology • Respiratory Diseases • Thrombocytopenia • ATM • IGH • TP53

Low Mortality from COVID-19 Infection in Patients with B-Cell Lymphoma after Bispecific CD20xCD3 Therapy (ASH 2023) - " A total of 130 patients who received bispecific CD20xCD3 antibodies (glofitamab or epcoritamab) as part of clinical trials in Denmark were assessed...Twelve patients (35%) received no specific treatment for COVID-19, while the most commonly prescribed treatments were sotrovimab in 13 patients (42%) and remdesivir in 9 patients (29%)... To our knowledge, this study presents the first data on COVID-19 incidence and severity in patients with relapsed/refractory lymphoma who have received CD3xCD20 bispecific antibodies. The COVID-19 attributable mortality after bispecific CD20xCD3 antibody therapy, when compared to CAR-T cell therapy, was much lower and comparable to the mortality reported in other cohorts of less heavily treated hematological malignancies infected with omicron variants. However, these patients present with considerable number of COVID-19 reactivations."

Clinical • B Cell Lymphoma • Cough • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pulmonary Disease • Respiratory Diseases

Activity of sotrovimab in early clearance of SARS CoV-2 infection in severe immunocompromised patients: results of a prospective, monocentric study. (PubMed, Infect Dis (Lond)) - "We enrolled considered 98 patients treated with nirmatrelvir/ritonavir or remdesivir...At the multivariate Cox regression analysis, therapy administration within 3 days from symptoms' onset (aHR 1.68; p = 0.031) and presumed sotrovimab effectiveness (aHR 1.75; p = 0.02) were found to be independent factors associated with for shorter time to viral clearance. The timing of administration of early antiviral therapy is crucial to reduce SARS-CoV-2 infection duration in immunocompromised patients and the combination with a mAb is associated with earlier viral clearance, as long asmAb is chosen among those effective against circulating variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Risk Factors for Persisting SARS-CoV-2 Infection in Patients with B-Cell Malignancies in the Omicron Era: A Multicenter Cohort Study. (PubMed, Int J Infect Dis) - "Our findings help define risk factors for persisting SARS-CoV-2 infection and support early treatment in patients with B-cell malignancies."

Journal • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases

AGILE (Early Phase Platform Trial for COVID-19) (clinicaltrials.gov) - P1/2 | N=600 | Recruiting | Sponsor: University of Liverpool | Active, not recruiting ➔ Recruiting | Trial completion date: Jul 2025 ➔ Oct 2026 | Trial primary completion date: Jul 2025 ➔ Oct 2026

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

An open-label phase II trial of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity. (PubMed, New Microbes New Infect) - "Sotrovimab pre-exposure prophylaxis had a favorable safety profile and was well tolerated at both doses, with low immunogenicity. These findings support mAbs' safety as COVID-19 pre-exposure prophylaxis in this population."

Journal • P2 data • Allergy • Immunology • Infectious Disease • Novel Coronavirus Disease • Pain • Respiratory Diseases

Reassessing sotrovimab's role in COVID-19: insights and implications. (PubMed, Lancet Infect Dis) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Sotrovimab versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. (PubMed, Lancet Infect Dis) - P3 | "In patients admitted to hospital with COVID-19 pneumonia, sotrovimab was associated with reduced mortality in the primary analysis population who had a high serum SARS-CoV-2 antigen concentration at baseline, but not in the overall population. Treatment options for patients admitted to hospital are limited, and mortality in those receiving current standard of care was high. The emergence of high-level resistance to sotrovimab among subsequent SARS-CoV-2 variants restricts its current usefulness, but these results indicate that targeted neutralising antibody therapy could potentially still benefit some patients admitted to hospital who are at high risk of death in an era of widespread vaccination and omicron infection."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Sotrovimab for Pre-exposure Prophylaxis against SARS-CoV2 in a Vulnerable Patient Population: Results from the PROTECT-V trial (IDWeek 2025) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Organoid-based neutralization assays reveal a distinctive profile of SARS-CoV-2 antibodies and recapitulate the real-world efficacy. (PubMed, Proc Natl Acad Sci U S A) - "The efficacy of VIR-7831, a class 3 anti-SARS-CoV-2 monoclonal antibody (mAb), was demonstrated repeatedly in clinical trials; yet, reduced neutralization against Omicron variants in cell-line-based neutralization assays led to its withdrawal from clinical use...Collectively, the robust organoid culture system and biologically relevant expression profiles of ACE2 and TMPRSS2 make nasal organoids present a correlate of in vivo protection of neutralizing mAbs exclusively. The organoid-based neutralization assays, superior to conventional cell-line-based assays, can recapitulate and predict the real-world efficacy of mAbs."

Journal • Real-world evidence • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • ACE2 • TMPRSS2

Pharmacological and Adjunctive Management of Non-Hospitalized COVID-19 Patients During the Omicron Era: A Systematic Review and Meta-Analysis. (PubMed, Viruses) - "Nirmatrelvir/ritonavir and remdesivir remain important for reducing severe outcomes, while sotrovimab retains partial efficacy. Rapid access to antivirals remains an important factor in mitigating SARS-CoV-2's burden."

Journal • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease. (PubMed, Sci Rep) - P4 | "MONET (EudraCT: 2021-004188-28) was multi-centric phase 4 open-label parallel randomized clinical trial, conducted in Italy over 2022-2023, to assess the efficacy of sotrovimab (SOT), tixagevimab/cilgavimab (TIX/CIL) and Nirmatrelvir/ritonavir (NMV/r), in outpatients at high risk for severe COVID-19. We found no evidence that viral variant was an effect measure modifier for the contrasts of interest (p = 0.14). Our analysis provides strong evidence that NMV/r exerts a greater in vivo antiviral effect than anti-Spike mAbs against Omicron sub lineages, confirming previous in vitro data."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases