etesevimab (JS016) / Chinese Academy of Sciences, Shanghai Junshi Biosci, Eli Lilly - LARVOL DELTA

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

CONDIVIDIAMO: COVID-19 and Disease Progression to the Severe Form: a Study on the Use of Monoclonal Antibodies Against SARS-CoV-2 (clinicaltrials.gov) - P=N/A | N=251 | Completed | Sponsor: University of Milano Bicocca | Recruiting ➔ Completed | N=1000 ➔ 251

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Comparison of bamlanivimab with or without etesevimab and casirivimab-imdevimab in clinical outcomes in patients with COVID-19: a systematic review and meta-analysis. (PubMed, J Chemother) - No abstract available

Clinical data • Journal • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease

Effects of N-glycan modifications on spike expression, virus infectivity, and neutralization sensitivity in ancestral compared to Omicron SARS-CoV-2 variants. (PubMed, PLoS Pathog) - "Finally, we found that loss of some N-glycans, including N343 and N234, increased the maximum percent neutralization by the class 3 S309 monoclonal antibody against D614G but not BA.1 variants, while these glycan deletions altered the neutralization potency of the class 1 COV2-2196 and Etesevimab monoclonal antibodies without affecting maximum percent neutralization. The maximum neutralization by some antibodies also varied with the glycan composition, with oligomannose-enriched pseudoviruses conferring the highest percent neutralization. These results highlight differences in the interactions between glycans and residues among SARS-CoV-2 variants that can affect spike expression, virus infectivity, and susceptibility of variants to antibody neutralization."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of JS026 and JS026 Together With JS016 for Treatment of COVID-19 (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Neutralizing anti-spike monoclonal antibodies for COVID-19 in vulnerable populations: lessons learned and future directions. (PubMed, Expert Opin Biol Ther) - "This article reviews the clinical trials that led to the emergency use authorization of bamlanivimab with or without etesevimab, casirivimab and imdevimab, sotrovimab, bebtelovimab, and tixagevimab and cilgavimab in the United States. Lessons learned from their clinical use should guide the future development of durable antibody-based therapies. A strategy that will preserve their therapeutic lifespan is needed."

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

BLAZE-1: A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (clinicaltrials.gov) - P2/3 | N=3307 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed | Trial completion date: Oct 2023 ➔ Feb 2023 | Trial primary completion date: Oct 2023 ➔ Feb 2023

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

Rational strategies for enhancing mAb binding to SARS-CoV-2 variants through CDR diversification and antibody-escape prediction. (PubMed, Front Immunol) - "Leveraging knowledge of the existing RBD-mAb interfaces and mutational space, we fine-tuned and redirected CT-p59 (Regdanvimab) and Etesevimab against the escaped variants through complementarity-determining regions (CDRs) diversification. We identified antibodies against the Omicron lineage BA.1 and BA.2 and Delta variants with comparable or better binding affinities to that of prototype Spike. This suggests that CDRs diversification by hotspot grafting, given an existing insight into the Ag-Abs interface, is an exquisite strategy to redirect antibodies against preselected epitopes and combat the neutralization escape of emerging SARS-CoV-2 variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Monoclonal Antibody Use for Coronavirus Disease 2019 in Pediatric Patients: A Multicenter Retrospective Study. (PubMed, J Pediatric Infect Dis Soc) - "Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died."

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

Insights on the interaction of SARS-CoV-2 variant B.1.617.2 with antibody CR3022 and analysis of antibody resistance. (PubMed, J Genet Eng Biotechnol) - "Characterization of antibody resistance for Delta variant with respect to the wild type gives understanding regarding why Delta variant endures the resistance boosted through several trademark vaccines. Several interactions with CR3022 have appeared compared to Wild for Delta variant, and hence, it is suggested that modification on the CR3022 antibody could further improve for the prevention of viral spread. Antibody resistance decreased significantly due to numerous hydrogen bond interactions which clearly indicate that these marketed/launched vaccines (etesevimab) will be effective for Delta variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Circulating microRNAs as emerging regulators of COVID-19. (PubMed, Theranostics) - "Currently, several drugs have been used in the clinical treatment of COVID-19, including antivirals (e.g., molnupiravir, baricitinib, and remdesivir), monoclonal antibodies (e.g., etesevimab and tocilizumab), protease inhibitors (e.g., paxlovid), and glucocorticoids (e.g., dexamethasone). Consequently, understanding the expression and mechanism of action of circulating miRNAs during SARS-CoV-2 infection will provide unexpected insights into circulating miRNA-based studies. In this review, we examined the recent progress of circulating miRNAs in the regulation of severe inflammatory response, immune dysfunction, and thrombosis caused by SARS-CoV-2 infection, discussed the mechanisms of action, and highlighted the therapeutic challenges involving miRNA and future research directions in the treatment of COVID-19."

Journal • Review • Cardiovascular • Hematological Disorders • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis • IL1B

A review of COVID-19 therapeutics in pregnancy and lactation. (PubMed, Obstet Med) - "Moving forward, diligent follow-up and documentation of outcomes in pregnant people treated with these agents will be essential to advance our understanding. Greater regulatory push and incentives are needed to ensure studies to obtain pregnancy data are expedited."

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

Cross-reaction of current available SARS-CoV-2 MAbs against the pangolin-origin coronavirus GX/P2V/2017. (PubMed, Cell Rep) - "Here, we find that CB6 (commercial name etesevimab), a COVID-19 therapeutic monoclonal antibody (MAb) developed by our group, efficiently inhibits GD/1/2019 but not GX/P2V/2017...Furthermore, we solve two complex structures of the GX/P2V/2017 RBD with MAbs belonging to RBD-1 and RBD-5, providing a structural basis for their different antigenicity. These results highlight the necessity for broad anti-coronavirus countermeasures and shed light on potential therapeutic targets."

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

"I got covid in January. I received monoclonal antibodies & had my scan. I had "considerable" shrinkage!! My doctor & Lilly won't do trial. This MUST be investigated! Etesevimab 700mg 20ml 2 vials Bamianivimab 700mg 20ml 1 vial PLEASE HELP" (@heatherrae106)

Novel Coronavirus Disease

SARS-CoV-2 evolves to reduce but not abolish neutralizing action. (PubMed, J Med Virol) - "Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants...Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Dual Monoclonal Antibodies on Sars-Cov-2 Alpha and Delta Variants: Clinical and Virological Efficacy. (PubMed, Microbiol Spectr) - "From 14 days following treatment initiation, we observed a slower viral load decay for patients treated with the bitherapy Bamlanivimab/Etsevimab compared to the Casirivimab/Imdevimab association therapy (P = 0.045)...Rapidly after initiation of the treatments, resistance mutations emerged in the interface between the MAbs and the target Spike glycoprotein, demonstrating the importance to continuously screen the viral genome during treatment course. Taken together, the results highlight that viral mutations may emerge under selective pressure, conferring a putative competitive advantage, and could rapidly spread, as observed for the Omicron variant."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Evolution of Anti-SARS-CoV-2 Therapeutic Antibodies. (PubMed, Int J Mol Sci) - "One of the conclusions of the review is that the EUA therapeutic antibodies that still retain efficacy against new VOCs bind an epitope formed by conserved residues that seem to be evolutionarily conserved as thus, critical for the RBD:hACE-2 interaction. The information reviewed here should help to design new and more efficacious antibodies to prevent and/or treat COVID-19, as well as other infectious diseases."

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

BLAZE-1: A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (clinicaltrials.gov) - P2/3 | N=3360 | Recruiting | Sponsor: Eli Lilly and Company | Completed ➔ Recruiting | Trial completion date: Dec 2021 ➔ Oct 2023 | Trial primary completion date: Feb 2021 ➔ Oct 2023

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

Characterization of Casirivimab Plus Imdevimab, Sotrovimab, and Bamlanivimab Plus Etesevimab-Derived Interference in Serum Protein Electrophoresis and Immunofixation Electrophoresis. (PubMed, J Appl Lab Med) - "Imdevimab can be added to the growing list of therapeutic monoclonal antibodies that produce sustained interference in SPEP/IFE. Although casirivimab and sotrovimab also produce assay interference in vitro, these antibodies are not reliably detected in serum from recently infused patients. The value of relative band position in recognizing bands that may represent therapeutic monoclonal antibodies is also emphasized. Clinicians and laboratorians should consider therapeutic monoclonal antibody interference in diagnostic SPEP/IFE and review a patient's medication list when new or transient monoclonal bands are identified."

Journal • Hematological Malignancies • Infectious Disease • Monoclonal Gammopathy • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Plasmacytoma

JS016 (Anti-SARS-CoV-2 Monoclonal Antibody)With Mild and Moderate COVID-19 or SARS-CoV-2 Asymptomatic Infection Subects (clinicaltrials.gov) - P1/2 | N=62 | Completed | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | Recruiting ➔ Completed | N=90 ➔ 62 | Trial completion date: Mar 2022 ➔ Aug 2021 | Trial primary completion date: Mar 2022 ➔ Aug 2021

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

Biophysical fitness landscape of the SARS-CoV-2 Delta variant receptor binding domain. (PubMed, J Mol Biol) - "All mutants showed similar binding affinity to ACE2 and to Class 1 antibodies (CC12.1 and LY-CoV016) as that of the wild-type. Delta double mutant L452R/T478K showed no binding to Class 2 antibodies (P2B-2F6 and LY-CoV555) and a hundred-fold weaker binding to a Class 3 antibody (REGN10987), and the decreased antibody binding is determined by the L452R mutation. These results indicate that the immune escape from neutralizing antibodies, rather than receptor binding, is the main biophysical parameter that determined the fitness landscape of the Delta variant RBD."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Pharmacological treatment of COVID-19: an opinion paper. (PubMed, Rev Esp Quimioter) - "The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation."

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

An EUA for bebtelovimab for treatment of COVID-19. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

CONDIVIDIAMO: COVID-19 and Disease Progression to the Severe Form: A Study on the Use of Monoclonal Antibodies Against SARS-CoV-2 (clinicaltrials.gov) - P=N/A | N=1000 | Recruiting | Sponsor: University of Milano Bicocca

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

BLAZE-1: A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (clinicaltrials.gov) - P2/3 | N=3290 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease