Evusheld (cilgavimab/tixagevimab) / AstraZeneca - LARVOL DELTA

Safety, Pharmacokinetics, and Predicted Neutralizing Activity of the SARS-CoV-2 Monoclonal Antibody Sipavibart: Results from Little DIPPER and the SUPERNOVA Substudy. (PubMed, Infect Dis Ther) - P1, P2/3 | "These results demonstrate the feasibility and appropriateness of conducting phase 1 and 2 studies to support rapid immunobridging analyses, and accelerate the delivery of new SARS-CoV-2-neutralizing monoclonal antibodies to immunocompromised individuals."

Journal • PK/PD data • Immunology • 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

Pharmacokinetic Comparability Assessment of Tixagevimab and Cilgavimab Developed for COVID-19 Prevention and Treatment Using Standard Exposure Metrics and Partial Area Under the Curve. (PubMed, Clin Pharmacokinet) - P1 | "Pharmacokinetic comparability of tixagevimab, cilgavimab and AZD7442 was demonstrated between the different treatments based on analyses using traditional bioequivalence metrics or pAUCs. Partial AUC could serve as an exposure metric when evaluating PK comparability for extended half-life mAbs."

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

Pre-Exposure Prophylaxis With Pemivibart in Adults With Hematologic Malignancies: A Single-Center Cohort (NCCN 2026) - " We included 180 pemivibart recipients; 159 (88.3%) were vaccinated and 90 (50.0%) had prior tixagevimab–cilgavimab. In this real-world single-center cohort, pemivibart pre-exposure prophylaxis was well tolerated and associated with low breakthrough infection rates and no COVID-19–related hospitalizations. These findings support integration of pemivibart into preventive care for adults with blood cancers while variant surveillance and durability studies continue. View Full Size CLO26-086: FIGURE."

Clinical • Cough • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Preventive care • Respiratory Diseases • Septic Shock

REAl LIfe" Observational Study on the Effectiveness of Evusheld Prophylaxis Against SARS-CoV-2 Omicron Variants in Vaccine Non-responder Immunocompromised Patients (clinicaltrials.gov) - P=N/A | N=88 | Completed | Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

New trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Incidence of severe COVID-19 in patients with chronic lymphocytic leukaemia or indolent B-cell non-Hodgkin lymphoma who received vaccination and pre-exposure prophylaxis with tixagevimab and cilgavimab in Italy: An observational study by the GIMEMA working party on chronic lymphoproliferative disorders and by the Fondazione Italiana Linfomi. (PubMed, Br J Haematol) - No abstract available

Journal • Observational data • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology

Impact of COVID-19 Monoclonal Antibody Therapy on Subsequent Vaccine-elicited SARS-CoV-2 Immune Responses. (PubMed, J Infect Dis) - P4 | "Prior anti-SARS-CoV-2 mAb treatment limits endogenous RBD-focused B-cell responses to later mRNA vaccination without measurably affecting T-cell immunity. Timing of vaccination after mAb therapy may matter and warrants study."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4 • CD8

Clinical outcomes of immunocompromised patients administered tixagevimab-cilgavimab as pre-exposure prophylaxis for COVID-19: real-world experience in Taiwan. (PubMed, Int J Infect Dis) - "Tixagevimab/cilgavimab -treated immunocompromised patients had a low rate of subsequent severe or critical COVID-19. Our study provides insights into the role of future monoclonal antibodies as COVID-19 pre-exposure prophylaxis among immunocompromised patients and emphasizes the need for ongoing research."

Clinical data • Journal • Real-world evidence • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Organ Transplantation • Solid Tumor • Transplantation

Stochastic Gates for Covariate Selection in Population Pharmacokinetics Modeling. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "In real clinical data from a monalizumab study, the method successfully identified covariates that matched those found by experts. However, for tixagevimab/cilgavimab, it identified a superset of covariates, indicating a potential need for further pruning. This machine learning-based method enhances the covariate preselection process in population pharmacokinetics model development, offering significant time savings and improving efficiency even under challenging scenarios."

Journal • PK/PD data

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

Safety and Pharmacokinetics of Repeat Dosing of Long-Acting SARS-CoV-2 Antibodies Tixagevimab/Cilgavimab (AZD7442): Results from the PROVENT Sub-study. (PubMed, Clin Drug Investig) - P3 | "AZD7442 safety, pharmacokinetic, and ADA response profiles were similar regardless of repeat dosing schedule, and consistent with single-dose study data. These results may support future use of long-acting antibodies."

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

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

Efficacy, safety, pharmacokinetics, immunogenicity, and serum neutralizing activity of AZD7442 (tixagevimab-cilgavimab) in hospitalized COVID-19 patients: long-term results from the DisCoVeRy trial. (PubMed, Clin Microbiol Infect) - "AZD7442 did not demonstrate any clinical benefit and was safe up to 15 months. This study also provides valuable data on the pharmacokinetics, immunogenicity, and neutralizing activity of AZD7442 in hospitalized COVID-19 patients."

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

Prophylactic role of tixagevimab/cilgavimab for COVID-19 in newly transplanted kidney recipients: Single-center experience and review of literature. (PubMed, World J Transplant) - "Tixagevimab/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."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Solid Organ Transplantation • Transplantation

Real World Evaluation of Evusheld in Prevention of COVID-19 in Immunocompromised Patients: An Observational Cohort Study. (PubMed, Am J Med Sci) - "Within six months of Evusheld administration, immunocompromised patients showed no episodes of rehospitalization, mechanical ventilation, or death, and experienced low rates of severe COVID-19."

HEOR • Journal • Observational data • Real-world evidence • Hematological Disorders • Hematological Malignancies • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor

Impact of COVID-19 in Patients with Chronic Lymphocytic Leukemia Treated with Venetoclax: A Possible Role of the Association to Anti-CD20 Antibody? a Multicentre Seifem Study (ASH 2023) - "The retrospective multicenter study included CLL patients treated since 2017 with venetoclax single agent until progression or toxicity or venetoclax plus anti-CD20 antibody (mainly rituximab as part of VR protocol for 24 months in relapsed/refractory patients or obinutuzumab as part of VO protocol for 12 months in untreated patients)...Prophylaxis with tixagevimab/cilgavimab was administered in less than 20% of the patients...Remdesivir was chosen as treatment in 48.9%, nirmatrelvir/ritonavir in 21.3%...The analysis found over a third of patients infected by SARS-CoV-2, in 57% of the cases the infection was grade 1-2 with a mortality rate of almost 10%, but higher if COVID-19 was of grade 3-4 (18.2%). We confirmed the association of anti-CD20 antibody to venetoclax as a risk factor for SARS-CoV-2 infection and mortality rate in patients with CLL and severe COVID-19."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Severe COVID-19 Infection in Patients with Chronic Lymphocytic Leukemia or Indolent B-Cell Non-Hodgkin Lymphoma Who Received Pre-Exposure Prophylaxis with Tixagevimab and Cilgavimab in Italy: Preliminary Results of the Observational Study By the Gimema Working Party on Chronic Lymphoproliferative Disorders and By the Fondazione Italiana Linfomi (ASH 2024) - P | "These patients respond poorly to vaccination, especially those receiving anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhibitors (BTKi) or the BCL2 inhibitor venetoclax...At 6 months from PrEP, 159/513 patients (31%) had a COVID-19 infection and 39% of these patients received an anti-viral treatment with nirmatrelvir/ritonavir or remdesivir...Noteworthy, 17/18 cases of severe COVID infection occurred in a period (August 2022-January 2023) in which the Omicron sub-variants BA.5 and BQ.1 were prevalent in Italy. In conclusion, in this population of CLL and iB-NHL at high risk for poor response to vaccination, the modern management strategy that included PrEP with tixagevimab and cilgavimab and treatment with antiviral drugs resulted in low rates of severe COVID infection and death."

Clinical • Observational data • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Waldenstrom Macroglobulinemia

Incidence and Management of COVID-19 Infections in Vaccinated Patients with CLL (ASH 2023) - P | "The incidence of COVID-19 was comparable amongst men and women in the initial cohort (4%, 2%) and booster cohort (25%, 24%) as well as those who received mRNA-1273 and BNT162b2 vaccines (2%, 4%) and (24%, 26%). There were no infections in the 6 pts who received Ad26.COV2.S in the initial cohort nor 4 in booster cohort. Infections by treatment in initial cohort: 1% of treatment-native, 4% BTKi, 7% CD20 mAb + venetoclax, 9% BTKi + venetoclax...All infections (8/8) occurred in the initial cohort prior to the receipt of tixagevimab/cilgavimab or in those who did not receive prophylaxis; 84% (27/32) in the booster cohort... There were 243 pts enrolled in the initial vaccine cohort from 03/21-09/21 and 129 in the booster cohort from 08/21-02/22; 73 pts from initial cohort enrolled into the booster cohort. Patient characteristics are in Table 1. Eight pts (3.3%) reported COVID-19 in the initial cohort within 1 year of receiving the initial vaccine or prior to receipt of a..."

Clinical • Chronic Lymphocytic Leukemia • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD20

The Efficacy and Safety of Tixagevimab/Cilgavimab (AZD7442) Against Sars-Cov-2 Omicron BA.5 for Patients with Hematologic Malignancies (ASH 2023) - "6%) received Rituximab-based therapy. Figure. Anti-SARS-CoV-2 spike protein antibody (Anti-S) titers after admistration of tixagevimab/cilgavimab (AZD7442/Evusheld)"

Clinical • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Respiratory Diseases

Efficacy and Safety of Tixagevimab-Cilgavimab (Evusheld or AZD7442) As Pre-Exposure Prophylaxis for COVID-19 Among Allogeneic Hematopoietic Stem Cell Transplant Recipients (ASH 2023) - "Our study found no evidence of efficacy of Evusheld against COVID-19 after Allo-HSCT transplant. This lack of efficacy may be attributed to the emergence of the XBB. 1."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cardiovascular • Chronic Myeloid Leukemia • Cytomegalovirus Infection • Diabetes • Dyslipidemia • Epstein-Barr Virus Infections • Graft versus Host Disease • Hematological Malignancies • Hypertension • Immunology • Infectious Disease • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome • Novel Coronavirus Disease • Oncology • Transplantation

Efficacy of Monoclonal Antibody Tixagevimab/Cilgavimab for Prevention of Sars-Cov-2 Infection Among Cancer Patients: Double Blined Randomized Placebo Controlled Trail (ProvMAB trial) (ASH 2023) - "DiscussionIn this study, we present our findings comparing Tixagevimab/Cilgavimab in immunocompromised patients who received over three doses of vaccination for the prevention of SARS-CoV-2 infection in patients with hematologic malignancies and Oncologic malignancies undergoing chemotherapy during the SARS-CoV-2 omicron surge. Our results suggest that booster vaccinations, beyond the standard three doses, were sufficient to protect against SARS-CoV-2 infection in this particular patient population, considering their ongoing standard of care during the pandemic variant in the future."

Clinical • Hematological Malignancies • Infectious Disease • Oncology • Respiratory Diseases

Pre-Graft Vaccination or Infection Do Not Provide More Protection Against COVID-19 Infections in Post-Graft Vaccinated Recipients of Allogeneic Stem Cell Transplantation (ASH 2023) - "Some pts also received tixagevimab and cilgavimab (Tix/cil) as preventive treatment after Allo-HSCT during the Delta wave...Conclusion : In this study, post-Allo-SCT vaccination appears to be of crucial importance to protect recipients against COVID-19 infections. Pre-graft vaccine or infection are not associated with less COVID-19 infections nor severe forms of the disease in pts vaccinated after transplant, suggesting that post-graft vaccination is sufficient to ensure good protection in these pts."

Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Novel Coronavirus Disease • Transplantation

Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation Agents (ASH 2023) - "Tixagevimab/cilgavimab lost its emergency use authorization as prevention for immunocompromised patients because of its lack of efficacy against newer variants. However, next-generation prevention agents are in development, including a new monoclonal antibody, AZD3152...PeerView's expert faculty will discuss strategies to engage patients with elevated risk of serious COVID-19 infection in the development of customized prevention plans. In addition, they will explore approaches to overcoming real-time barriers to access and use of available options for prevention of serious COVID-19 illness."

Clinical • Hematological Malignancies • Infectious Disease • Novel Coronavirus Disease • Oncology