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

Wastewater-Based Genomic Surveillance of SARS-CoV-2 Antiviral Resistance Determinants in Ontario: Towards a Scalable Framework for Population-Level Antiviral Resistance Monitoring. (PubMed, Viruses) - "These findings demonstrate that wastewater surveillance enables population-scale monitoring of antiviral resistance and immune escape-associated mutations and offers a scalable model for broader surveillance."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

EPIC: A NON-INTERVENTIONAL, OBSERVATIONAL STUDY OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS TREATED WITH FIRST-LINE ACALABRUTINIB THROUGH THE UK EARLY ACCESS PROGRAMME. INTERIM ANALYSIS UP TO 24 MONTHS (EHA 2023) - P=N/A | "The most common treatment received for COVID-19 (for 32% of patients; 6/19) was sotrovimab. This first IA shows an 81.1% (95% CI, 71.3%–92.4%; n=53) acalabrutinib real-world continuation rate at 12 months in treatment-naïve patients with CLL. Future analyses are aiming at including retrospective data from around 40 clinical sites with approximately 350 eligible patients. Chronic lymphocytic leukemia, Real world data"

Clinical • Observational data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • ATM • IGH • TP53

Immunobridging Analysis of Pemivibart for the Treatment of COVID-19: A Therapeutic Gap for the Immune-Compromised Population Remains. (PubMed, Open Forum Infect Dis) - "Complementary 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...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...Following 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."

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

Prolonged SARS-CoV-2 infection in hematologic malignancies: clinical impact, risk factors and intra-host viral evolution. (PubMed, Front Immunol) - "Viral intra-host mutations across the entire viral genome, predominantly within the spike were detected in most patients with prolonged COVID-19, especially in those who received anti-SARS-CoV-2 mAb as sotrovimab (E340, R346, K356) and tixagevimab/cilgavimab (R346, K444 and G446). Prolonged SARS-CoV-2 infection in hematologic patients is frequent and leads to persistent viral replication, significant morbidity and the emergence of intra-host viral mutations. Optimizing treatments and monitoring viral clearance are medical needs for high-risk patients."

Journal • Observational data • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases

Challenges and Opportunities for Signal Detection During Public Health Emergencies: An Historical Re-evaluation of the Disproportionality Analysis of the ADR Reporting of Anti-COVID-19 Monoclonal Antibodies in Vigibase. (PubMed, Drug Saf) - "This analysis identified potential cardiovascular and neurological safety signals, which will remain unexplored by longitudinal pharmacoepidemiologic studies due to the withdrawal of these agents from clinical use. Overall, this case study supported the full implementation of near real-time multimodal approaches to efficiently perform actionable signal management during public health emergencies."

Journal • Atrial Fibrillation • Cardiovascular • CNS Disorders • Infectious Disease • Myocardial Infarction • Novel Coronavirus Disease • Respiratory Diseases

Optimizing drug combinations to resurrect the potency of failed antibody therapy against emerging COVID-19 variants using IDentif.AI. (PubMed, Front Digit Health) - "For instance, multiple therapeutics like Evusheld are no longer effective against current variants and therefore have their emergency use authorizations (EUA), a regulatory mechanism allowing emergency use of medical products, revoked until further notice. Similarly, sotrovimab (STV), a human neutralizing monoclonal antibody (MAB), received EUA in May 2021 and was later granted authorization for COVID-19 treatment in Singapore...IDentif.AI-pinpointed STV/EIDD-1931 and STV/GS-441524 combinations were able to interact synergistically to enhance efficacy against XBB and importantly, substantially reduce STV's in vitro EC50 (half maximal effective concentration) by up to 7-fold. This optimization platform represents a strategic approach to rapidly repurpose existing or previously failed therapeutics and subsequently restore their efficacy against a disease indication by pairing them with the correct drugs in combinations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

AGILE (Early Phase Platform Trial for COVID-19) (clinicaltrials.gov) - P1/2 | N=600 | Recruiting | Sponsor: University of Liverpool | Trial completion date: Jul 2026 ➔ Mar 2027 | Trial primary completion date: Jul 2026 ➔ Mar 2027

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

Glycan shielding and epitope reorganization drive sotrovimab resistance in SARS-CoV-2 Omicron variants. (PubMed, Arch Biochem Biophys) - "Notably, mutation-induced reorientation and increased mobility of the conserved N343-linked glycan enhances steric shielding of the sotrovimab epitope and perturbs key glycan-mediated stabilizing interactions, amplifying sotrovimab-escape despite limited direct epitope mutation. Together, these results establish that sotrovimab resistance in Omicron BA.1 and BA.2 arises from a synergistic interplay of RBD conformational destabilization, weakened interfacial energetics, disrupted dynamic coupling, and glycan-mediated epitope shielding."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A cocktail of SARS-CoV-2 S stem helix domain and receptor binding domain human monoclonal antibodies prevents the emergence of viral escape mutants. (PubMed, Microbiol Spectr) - "Serial passaging of Δ3a7b-Nluc under selective pressure identified a 1301B7 antibody-resistant mutant (ARM-B7) harboring an RBD mutation (S371F) that conferred resistance to 1301B7 and other RBD-directed NAbs (casirivimab, SC27, and sotrovimab)...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 emergence of NAb-induced escape mutations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

RECOVERY: Randomised Evaluation of COVID-19 Therapy (clinicaltrials.gov) - P3 | N=70000 | Recruiting | Sponsor: University of Oxford | Trial completion date: Jun 2036 ➔ Sep 2038 | Trial primary completion date: Jun 2026 ➔ Sep 2028

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

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

Fc-engineered antibodies enhance protection against SARS-CoV-2 lung infection and inflammation. (PubMed, mBio) - "Modified versions of S309, the parent of the clinically used sotrovimab antibody, more effectively reduce viral burden and inflammation in the lung and shape protective transcriptional responses, which, together, result in improved lung ventilatory function and outcome after SARS-CoV-2 infection. Thus, antibody engineering can serve as a strategy to enhance therapeutic activity against rapidly evolving viruses with the potential to escape neutralization."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CCR2

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