Evusheld (cilgavimab/tixagevimab) / AstraZeneca - LARVOL DELTA

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

Safety, Tolerability, and Pharmacokinetics of the Long-Acting SARS-CoV-2-Neutralizing Monoclonal Antibody Combination AZD7442 (Tixagevimab/Cilgavimab) in Healthy Chinese Adults. (PubMed, Clin Pharmacol Drug Dev) - "SARS-CoV-2-neutralizing antibody titers were more than 4-fold higher than baseline levels by Day 8, then decreased through Day 361 following AZD7442 administration. AZD7442 was well tolerated in healthy Chinese adults, demonstrating predictable pharmacokinetics and an extended half-life consistent with previous studies."

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

COVID-19 Vaccine Boosters in People With Multiple Sclerosis: Improved SARS-CoV-2 Cross-Variant Antibody Response and Prediction of Protection. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "Despite not eliciting adequate antibody response in pwMS on IMM-DMT, COVID-19 boosters improve the breadth of the humoral response against SARS-CoV-2 emerging variants. Vaccine protection can be predicted by statistical modeling."

Journal • Observational data • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Respiratory Diseases

Effectiveness of full mRNA vaccinations to prevent COVID-19 among immunocompromised patients receiving tixagevimab-cilgavimab as pre-exposure prophylaxis-authors' response. (PubMed, J Formos Med Assoc) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Clinical outcomes in kidney transplant recipients receiving tixagevimab/cilgavimab for outpatient treatment of COVID-19: a single-center retrospective study. (PubMed, Front Transplant) - "These real-world data further support that outpatient treatment with monoclonal antibodies such as tixagevimab/cilgavimab can prevent clinical deterioration in kidney transplant recipients during a period of Omicron dominance. Novel therapeutics are needed for variants for which tixagevimab/cilgavimab shows no neutralization."

Clinical data • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Transplantation

Unveiling protection: a meta-analysis of tixagevimab-cilgavimab prophylaxis in 28,950 transplant recipients and immunocompromised patients against COVID-19. (PubMed, Virol J) - "Tixagevimab-cilgavimab offers a significant protective effect against COVID-19, including Omicron variants, in immunocompromised patients, underscoring its role as an effective pre-exposure prophylaxis. Future studies should further explore its efficacy across different SARS-CoV-2 variants and potential synergies with vaccination efforts."

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

Dose-dependent impact of tixagevimab-cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals. (PubMed, Sci Rep) - "This was most evident in immunocompromised individuals when variants neutralized by tixagevimab-cilgavimab in vitro were circulating; effectiveness 74%. Supports a proof of concept for monoclonal antibodies in immunocompromised individuals as a prevention strategy against novel viruses."

Journal • Retrospective data • Bone Marrow Transplantation • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Transplantation

Expanded Analysis of in vivo-delivered SARS-CoV-2 Plasmid DNA-encoded Monoclonal Antibodies (DMAb) in a Phase 1 Clinical Trial in Healthy Adults (ASGCT 2025) - P1 | "In this study, we evaluated in vivo gene delivery of a DMAb cocktail encoding AZD5396 and AZD8076, modified versions of the SARS-CoV-2 neutralizing mAb cocktail Evusheld... In parallel with the durable in vivo expression profile, these data highlight the biologic activity of an in vivo-expressed synthetic DNA-delivered mAb cocktail and are supportive of further development as a strategy for delivery of antibody-based gene-encoded biologic drugs. Disease Focus of Abstract:Infectious Disease"

P1 data • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Evusheld Japan PMS_Japan Post-Marketing Surveillance (PMS) (clinicaltrials.gov) - P=N/A | N=366 | Completed | Sponsor: AstraZeneca | Trial completion date: Sep 2024 ➔ Jan 2025 | Trial primary completion date: Sep 2024 ➔ Jan 2025

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

A FIH dose-escalation trial of the safety and pharmacokinetics of anti-SARS-CoV-2 DNA-encoded monoclonal antibodies (DMAb) formulated for delivery by CELLECTRA in healthy adults (ASGCT 2025) - P1 | " This multi-group Phase 1 dose-escalation study (NCT05293249) investigates the intramuscular (IM) administration of a pDNA cocktail encoding AZD5396 and AZD8076, modified for in vivo delivery and expression of the SARS-CoV-2 neutralizing mAb cocktail Evusheld... This study provides the first clinical proof-of-concept for synthetic pDNA DMAb technology, demonstrating durable in vivo production of functional monoclonal antibodies. The findings underscore the importance of synthetic design, formulation, and delivery in achieving biologically relevant gene-encoded biologics expression. The DMAb platform may represent a valuable strategy for targeting a wide range of diseases treatable with monoclonal antibodies or their derivatives."

Clinical • IO biomarker • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Immune Modulation and Efficacy of Tixagevimab/Cilgavimab Pre-Exposure Prophylaxis in Lung Transplant Recipients During the Omicron Wave. (PubMed, Int J Mol Sci) - "This finding aligns with IL-18's primary role in stimulating type-1 T helper (Th1) cell responses, necessary for the induction of virus-specific cytotoxic T lymphocytes (CTLs). These results suggest that tixagevimab/cilgavimab may induce a systemic immune signature that could contribute to priming the immune response against SARS-CoV-2, potentially mediated by interactions with immune cell subsets."

Journal • Immune Modulation • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Transplantation • IL18

Comparative Analysis of Early COVID-19 Treatment Efficacy in a Multicentric Regional Cohort in Italy: Emulation of a Series of Target Trials. (PubMed, J Med Virol) - "Participants received either nirmatrelvir/ritonavir (NMV/r), molnupiravir (MLP), remdesivir (RDV), sotrovimab (SOT), or tixagevimab/cilgavimab (TIX/CIL). Weighted analysis showed that NMV/r and MLP were superior to all other interventions. In our population of individuals at high risk of progression to severe disease, there was clinical benefit in using NMV/r or MLP instead of mAbs-based therapies or RDV."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease

Comment on "Effectiveness of full mRNA vaccinations to prevent COVID-19 among immunocompromised patients receiving tixagevimab-cilgavimab as pre-exposure prophylaxis". (PubMed, J Formos Med Assoc) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Effectiveness of early intervention and combination treatment with monoclonal antibodies and antivirals in oncohematological patients with SARS-CoV-2: a retrospective experience. (PubMed, Front Immunol) - "We focused on the impact in patients with COVID-19 related pneumonia of specific therapies, early treatment, and tixagevimab-cilgavimab prophylaxis on in-hospital mortality and viral clearance time...This group also showed a significant reduction in the time to viral clearance from the first day of the evaluated therapy (6 days [IQR 4;9]), compared to patients treated with only remdesivir (17 days [IQR 8;37]) (p=0.03)...These results, in line with recent studies, underscore the critical importance of prompt treatment and a multitargeted pharmacological approach for optimizing outcomes in oncohematological patients with SARS-CoV-2. Future research, involving larger cohorts, should delve deeper into COVID-19 treatment strategies for this vulnerable population, with a particular emphasis on the elderly, who continue to experience high mortality rates."

Journal • Retrospective data • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases

Effectiveness of full mRNA vaccinations to prevent COVID-19 among immunocompromised patients receiving tixagevimab-cilgavimab as pre-exposure prophylaxis. (PubMed, J Formos Med Assoc) - "The Kaplan-Meier estimate showed a lesser trend of breakthrough infections with those receiving full vaccinations (P = 0.08). Our study underscores the importance of full vaccinations among immunocompromised patients receiving pre-exposure prophylactic mAbs against COVID-19."

Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

De Novo DSA and Antibody-Mediated Rejection in Heart Transplant Patients After COVID-19 or Evusheld Administration: A Case Series (ISHLT 2025) - "Patient outcomes and responses to therapies such as plasmapheresis and rituximab were documented.Results Of the nine patients, six developed AMR within 1 year of transplantation following COVID-19 infection or Evusheld administration, while three developed late AMR. The findings underscore the need for vigilant monitoring and timely intervention in transplant recipients who experience COVID-19 or receive prophylactic monoclonal antibody therapies. These cases highlight the importance of managing viral infections aggressively to prevent immune activation and graft injury in this vulnerable population."

Clinical • Antibody-mediated Rejection • Infectious Disease • Novel Coronavirus Disease • Transplantation • NPPB

AstraZeneca showcases innovation in infectious disease protection at ESCMID Global 2025 (AstraZeneca Press Release) - "AstraZeneca will share new data across its Vaccines & Immune Therapies portfolio at the 2025 Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global 2025) in Vienna, Austria, from 11-15 April 2025. With 13 abstracts, including two oral presentations and two late-breaking poster presentations, the Company will highlight progress in advancing novel immunisations against bacterial and viral infectious diseases and share real-world evidence showing the burden of respiratory viral infections and the continued need for protection."

Clinical data • Preclinical • Bronchiectasis • Infectious Disease • Influenza • Respiratory Diseases

ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA AND NONSPECIFIC INTERSTITIAL PNEUMONIA ASSOCIATED WITH ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANTATION. CASES REPORT (EBMT 2025) - "A 36-year-old man with AML underwent allo-HSCT on 08.06.23 from a matched unrelated donor after RIC (fludarabine/busulfan) and prophylaxis of GVHD with Cy 100 mg/kg, MMF, CSА...Second allo-HSCT was on 19.07.23 from a haploidentical father with a treosulfan-based regimen...BAL was pathogen-negative, and empirical ceftaroline therapy was initiated.Despite treatment, respiratory failure progressed, requiring high-flow oxygen...Antimicrobial therapy was adjusted (trimethoprim/sulfamethoxazole, piperacillin/tazobactam, moxifloxacin, and "Evusheld"). Prednisolone (1 mg/kg/day) and FAM were started on 01.12.2023 with partial improvement.SARS-CoV-2 was detected, and molnupiravir was administered...Ruxolitinib (20 mg/day) was started on 22.01.2024, leading to improvement observed on subsequent CT scans...Antimicrobial therapy (voriconazole, meropenem, levofloxacin, polymyxin) stabilized her condition... We report two cases of rare ILDs: AFOP and NSIP. Currently, there..."

Case report • Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Cough • Graft versus Host Disease • Immunology • Infectious Disease • Interstitial Lung Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Transplantation

New Function for Safety Signal Monitoring in MID-NET®: The Case of an Anti-COVID-19 Drug. (PubMed, Clin Transl Sci) - "We monitored the safety signals of an anti-COVID-19 drug (combination of tixagevimab and cilgavimab) and compared them with those of two controls (peramivir and the combination of casirivimab and imdevimab) to examine the practical utility of this new tool. Our study provided helpful information (e.g., new safety signals) on many outcomes at multiple time points, which could enhance the understanding of drug safety profiles soon after approval. Our function can be used to rapidly and continuously monitor drug safety signals and contribute to strengthening drug safety monitoring in Japan."

Journal • Infectious Disease • Novel Coronavirus Disease

Clinical outcomes of immunocompromised patients using tixagevimab-cilgavimab as pre-exposure prophylaxis for COVID-19: real-world experience in Taiwan (ESCMID Global 2025) - No abstract available

Clinical • Clinical data • Real-world • Real-world evidence • Infectious Disease • Novel Coronavirus Disease

Pharmacokinetics and immunogenicity of AZD7442 (Tixagevimab/Cilgavimab) in hospitalised COVID-19 patients: results from the DisCoVeRy trial (ESCMID Global 2025) - No abstract available

Clinical • PK/PD data • Infectious Disease • Novel Coronavirus Disease

Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies. (PubMed, iScience) - "SARS-CoV-2 neutralizing antibodies increased 157-fold at 7 days and 127-fold at 1 month (IM-treated) but were less robust in IV participants. These data can inform future development of monoclonal antibodies against SARS-CoV-2 and other viruses, even if this intervention is of low utility for contemporary SARS-CoV-2 variants."

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

Effectiveness of pharmacological treatments for COVID-19 due to SARS-CoV-2: a systematic literature review. (PubMed, Front Pharmacol) - "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). According to this systematic review, the treatments with the greatest evidence of reducing mortality in patients with COVID-19 are remdesivir and tocilizumab."

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

Impact of SARS-CoV-2 variant mutations on susceptibility to monoclonal antibodies and antiviral drugs: a non-systematic review, April 2022 to October 2024. (PubMed, Euro Surveill) - "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). 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..."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • SPECC1

Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study: Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study (clinicaltrials.gov) - P2/3 | N=3882 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4