bamlanivimab/etesevimab (LY-CoV555/LY-CoV016) / Eli Lilly - LARVOL DELTA

Effectiveness and Safety of Outpatient Monoclonal Antibody Use for the Treatment of COVID-19 in Children and Adolescents: Single Center Study. (PubMed, J Pediatr Pharmacol Ther) - "Monoclonal antibodies appear to be safe and effective in preventing hospitalizations in COVID-19-positive children."

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

Prevention of COVID-19 Complications in High-risk Subjects Infected by SARS-CoV-2 and Eligible for Treatment Under a Cohort ATU ('Autorisation Temporaire d'Utilisation') OR or Authorisation for Early Access (AAP). A Prospectvie Cohort. (clinicaltrials.gov) - P=N/A | N=756 | Completed | Sponsor: ANRS, Emerging Infectious Diseases | Recruiting ➔ Completed | N=2000 ➔ 756

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CCL3 • CXCL8 • IL15 • IL1R1 • IL7

Serum IL-6 and PTX3 predict severe outcome from COVID-19 in ambulatory subjects: Impact for future therapeutic decisions. (PubMed, PLoS One) - "To that end, we used samples from SARS-CoV-2-infected individuals from the placebo arm of the BLAZE-1 clinical trial who progressed to hospitalization or death compared to individuals in the same study who did not require medical intervention and investigated whether baseline serum cytokines and chemokines could predict severe outcome...Moreover, a two-marker model incorporating levels of both IL-6 and PTX3 further improved the prediction over the addition of a single protein marker to an AUC of ROC = 0.91. While the analytes identified in this study have been well-documented to be altered in SARS-CoV-2 infection, this analysis demonstrates the potential value of their use in predicting hospitalization or death in ambulatory participants infected with SARS-CoV-2 and could guide early treatment decisions."

Biomarker • Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CXCL10 • IL1R1 • IL6 • PTX3

Effectiveness of Anti-SARS-CoV-2 monoclonal antibodies in real-life: RNAemia and clinical outcomes in high-risk COVID-19 patients. (PubMed, PLoS One) - "Early administration of anti-SARS-CoV-2 mAbs in high-risk patients significantly reduced viral loads in NPS and plasma and improved clinical outcomes. Despite the presence of RNAemia, these tailored mAb therapies led to favorable recovery times and minimal adverse effects."

Clinical data • 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

Mutational Scanning and Binding Free Energy Computations of the SARS-CoV-2 Spike Complexes with Distinct Groups of Neutralizing Antibodies: Energetic Drivers of Convergent Evolution of Binding Affinity and Immune Escape Hotspots. (PubMed, Int J Mol Sci) - "In this study, we conducted a comprehensive structural and energetic analysis of SARS-CoV-2 spike receptor-binding domain (RBD) complexes with neutralizing antibodies from four distinct groups (A-D), including group A LY-CoV016, group B AZD8895 and REGN10933, group C LY-CoV555, and group D antibodies AZD1061, REGN10987, and LY-CoV1404...The results demonstrate excellent qualitative agreement between the predicted binding hotspots and the latest experiments on antibody escape. These findings provide valuable insights into the molecular determinants of antibody binding and viral escape, highlighting the importance of targeting conserved epitopes and leveraging combination therapies to mitigate the risk of immune evasion."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Innate and SARS-CoV-2 specific adaptive immune response kinetic in neutralizing monoclonal antibody successfully treated COVID-19 patients. (PubMed, Int Immunopharmacol) - "Aim of the study was to compare the kinetic of innate and adaptive immune response as well as the SARS-CoV-2 specific humoral and T cell response in two groups of SARS-CoV-2-infected patients treated with two different mAbs regimens: Bamlanivimab/Etesevimab (BAM/ETE) or Casirivimab/Imdevimab (CAS/IMD). In conclusion, these results show similar effects of both mAb regimens in restoring T and NK cell homeostasis and in reducing inflammation. In contrast, CAS/IMD allows a better humoral and cellular SARS-CoV2 specific immunization."

IO biomarker • Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CD4 • CD8 • IFNG • IL6 • KLRC1 • PRF1

Comparison of Dual Monoclonal Antibody Therapies for COVID-19 Evolution: A Multicentric Retrospective Study. (PubMed, Viruses) - "A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group."

Clinical • Journal • Retrospective data • CNS Disorders • Depression • Infectious Disease • Novel Coronavirus Disease • Psychiatry • Respiratory Diseases

Adverse events associated with SARS-CoV-2 neutralizing monoclonal antibodies using the FDA adverse event reporting system database. (PubMed, Toxicol Res) - "In this study, data from the FAERS from January 2020 to December 2022 were used to investigate signals associated with five monoclonal antibody products (bamlanivimab, bamlanivimab/etesevimab, bebtelovimab, casirivimab/imdevimab, sotrovimab) in coronavirus disease 2019 (COVID-19) patients and one monoclonal antibody product (tixagevimab/cilgavimab) in patients wherein COVID-19 vaccination was not recommended. Even though the purposes of use were different, the types of signals between drugs were similar. Careful monitoring of these AEs should be considered for certain COVID-19 patients, at risk, when they are treated with monoclonal antibody products."

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

Impact analysis of SARS-CoV-2 vaccination in patients treated with monoclonal antibodies: A monocentric experience. (PubMed, Int Immunopharmacol) - "Key findings include a shorter duration of virological clearance in vaccinated outpatients but no significant differences in worsening or mortality rates between vaccinated and unvaccinated patients treated with mAbs. The study suggests a potential synergistic role of mAbs in accelerating virological clearance in vaccinated patients with mild to moderate COVID-19, with differing effects in hospitalized patients. Therefore, it is essential to implement health surveillance in high-risk patients with comorbidities in order to identify early any variants that might otherwise escape neutralizing antibodies."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Monoclonal antibodies against SARS-CoV-2 to prevent COVID-19 worsening in a large multicenter cohort. (PubMed, Heliyon) - "Among 1534 subjects (median [interquartile range, IQR] age 66.5 [52.4-74.9] years, 693 [45.2 %] women), 632 (41.2 %) received bamlanivimab ± etesevimab, 209 (13.6 %) casirivimab/imdevimab, 586 (38.2 %) sotrovimab, 107 (7.0 %) tixagevimab/cilgavimab...MAbs real-world data over a 2-year changing pandemic landscape showed the feasibility of the intervention, although the hospitalization rate was not negligible. Immunosuppressed subjects remain more at risk of clinical worsening."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy and Safety of Low-Dose, Rapidly Infused Bamlanivimab and Etesevimab: Phase 3 BLAZE-1 Trial for Mild-to-Moderate COVID-19. (PubMed, Infect Dis Ther) - P2/3 | "Consistent with previous studies, patients treated with BAM + ETE (350/700 mg) had a significantly lower proportion of PHVL and greater reduction in viral load compared with placebo. The overall safety profile is consistent with higher doses of BAM + ETE. Infusions of over ~ 8 min did not result in meaningful increase in incidence of TEAEs compared to higher doses of BAM + ETE administered over 30-60 min."

Journal • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Clinical outcomes in patients with mild to moderate coronavirus disease 2019 treated with monoclonal antibody therapy versus an untreated control cohort. (PubMed, Antivir Ther) - "Individuals treated with MAT had lower rates of 30-day COVID-19-related ED visits and hospital admissions compared to those not receiving MAT. Early MAT resulted in lower 30-day mortality compared to receipt >2 days post COVID-19 diagnosis."

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

Sotrovimab in the treatment of coronavirus disease-2019 (COVID-19): a systematic review and meta-analysis of randomized clinical trials. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The total population consisted of 5470 patients with COVID-19, 1921 (35%) in the sotrovimab group and 3549 (65%) in the control group (placebo or BRII-196 + BRII-198 or casirivimab + imdevimab or bamlanivimab + etesevimab, administered in a similar way to sotrovimab, in a single dose with a 60-min intravenous infusion)...The use of sotrovimab in the treatment of patients with COVID-19 had no significant impact on mortality and need for mechanical ventilation and did not appear to be safer compared to controls. However, there was evidence of effectiveness in reducing the rate of hospitalization, although the certainty of the evidence is moderate and the risk of bias is high."

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

Biophysical principles predict fitness of SARS-CoV-2 variants. (PubMed, Proc Natl Acad Sci U S A) - "We developed a biophysical model that uses statistical mechanics to map the molecular phenotype space, characterized by dissociation constants of RBD to ACE2, LY-CoV016, LY-CoV555, REGN10987, and S309, onto an epistatic fitness landscape. Our study sheds light on the impact of specific mutations on viral fitness and delivers a tool for predicting the future epidemiological trajectory of previously unseen or emerging low-frequency variants. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effect of Bamlanivimab as Monotherapy or in Combination with Etesevimab or Sotrovimab on Persistently High Viral Load in Patients with Mild-to-Moderate COVID-19: A Randomized, Phase 2 BLAZE-4 Trial. (PubMed, Infect Dis Ther) - P2 | "The study demonstrated that a significantly lower proportion of patients with mild-to-moderate COVID-19 treated with BAM or BAM + (ETE or sotrovimab) experienced a PHVL at day 7."

Combination therapy • Journal • Monotherapy • P2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Impact of BA.1, BA.2, and BA.4/BA.5 Omicron mutations on therapeutic monoclonal antibodies. (PubMed, Comput Biol Med) - "We conducted a systematic molecular dynamics (MD) simulation to investigate how the RBD mutations of these subvariants affect the interactions with broad mAbs including AstraZeneca (COV2-2196 and COV2-2130), Brii Biosciences (BRII-196), Celltrion (CT-P59), Eli Lilly (LY-CoV555 and LY-CoV016), Regeneron (REGN10933 and REGN10987), Vir Biotechnology (S309), and S2X259. We introduce a mutational escape map for each mAb to identify the key RBD sites and the corresponding critical mutations. Overall, our findings suggest that the majority of therapeutic mAbs have diminished or missing activity against Omicron subvariants, indicating the urgent need for a new therapeutic mAb with a better design."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety of Anti-SARS-CoV-2 Monoclonal Antibody Therapies: Clinical Characteristics and Outcomes of Adverse Drug Reactions (ACAAI 2023) - "Methods A retrospective chart review of adults with ADRs to SARS-CoV-2 mAbs (1) Bamlanivimab, (2) Bamlanivimab/Etesevimab, (3) Bebtelovimab, and (4) Tixagevimab/Cilgavimab between October 2020 and June 2022 was performed...Eleven patients met criteria for anaphylaxis: Bamlanivimab: n=9 and Bamlanivimab/Etesevimab: n=2 (required epinephrine)...Bamlanivimab was implicated in anaphylactic reactions and had more ADRs requiring hospitalization than other mAbs. Although these mAbs are ineffective against Omicron sub-variants, this data is useful for developing and safely monitoring new SARS-CoV-2 mAbs."

Adverse drug reaction • Clinical • Allergy • Cough • Fatigue • Immunology • Infectious Disease • Novel Coronavirus Disease • Pain • Pulmonary Disease • Respiratory Diseases

The Efficacy and Safety of Monoclonal Antibody Treatments Against COVID-19: A Systematic Review and Meta-analysis of Randomized Clinical Trials. (PubMed, Acta Med Indones) - "Tocilizumab should be used for severe to critical COVID-19 because it is not harmful and can improve mortality risk, mechanical ventilation, and hospital discharge. Bamlanivimab-Etesevimab and REGN-COV2 reduced viral load in mild-moderate outpatients."

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

Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping. (PubMed, Front Mol Biosci) - "Some nAbs, such as Sotrovimab, have exhibited varying levels of efficacy against different variants, while others, such as Bebtelovimab and Bamlanivimab-etesevimab are ineffective against specific variants, including BQ.1.1 and XBB. We identified two broad-spectrum mAbs, R200-1F9 and R207-2F11, as potential candidates with increased binding affinity to XBB.1.5 and BQ.1.1 compared to the reference (Wu01) strain. Additionally, we propose that these mAbs do not interfere with Angiotensin Converting Enzyme 2 (ACE2) and bind to conserved epitopes on the receptor binding domain of Spike that are not-overlapping, potentially providing a solution to neutralize these new variants either independently or as part of a combination (cocktail) treatment."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Antiviral Drugs and Vaccines for Omicron Variant: A Focused Review. (PubMed, Can J Infect Dis Med Microbiol) - "Omicron is nonsusceptible to REGEN-COV™ and bamlanivimab with etesevimab. Drugs that are effective against the Omicron variant are oral antiviral drugs such as Paxlovid (nirmatrelvir/ritonavir), remdesivir, sotrovimab, and molnupiravir...LY-CoV1404 (bebtelovimab) is recently authorized as it is effective against all sublineages of the Omicron variant...The neutralizing antibody response against Omicron elicited by the bivalent vaccine is superior to that of the ancestral Wuhan strain, without any safety concerns. For future advances, the ribosome display technology can be applied for the generation of human single-chain fragment variable (scFv) antibodies from B cells of recovered patients against Omicron and other Coronavirus variants as they are easier and faster to produce and have high affinity and high specificity."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

A Comparison of the Adverse Effects and Utility of Different Monoclonal Antibodies for SARS-CoV-2: A Retrospective Cohort Study. (PubMed, Cureus) - "Five hundred forty-two patients received bamlanivimab plus etesevimab; 849 received bebtelovimab; 1577 received casirivimab plus imdevimab; and 281 received sotrovimab...Bamlanivimab-etesevimab was associated with the highest adverse event rate (4.6%), and sotrovimab was associated with the lowest adverse event rate (1.4%) (p < 0.001)...There was a high degree of patient-reported symptom improvement, and adverse reactions were reported in only 2.2% of patients with no severe reactions. Multiple monoclonal antibody treatments are not effective as monotherapy; however, this study shows the potential benefits of including a mAb infusion as part of a SARS-CoV-2 treatment plan."

Adverse events • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Use of Monoclonal Antibodies in Pregnant Women Infected by COVID-19: A Case Series. (PubMed, Microorganisms) - "Pregnant COVID-19 patients receiving sotrovimab obtained better clinical outcomes. Pregnancy or neonatal complications were not observed after monoclonal treatment, confirming the safety and tolerability of these drugs in pregnant women."

Journal • Allergy • Infectious Disease • Novel Coronavirus Disease

Preliminary Evidence of Good Safety Profile and Outcomes of Early Treatment with Tixagevimab/Cilgavimab Compared to Previously Employed Monoclonal Antibodies for COVID-19 in Immunocompromised Patients. (PubMed, Biomedicines) - "Early treatment of SARS-CoV-2 infection with TIX/CIL showed favourable outcomes in a small group of immunocompromised patients, reporting no significant difference compared to similar patients treated with other mAbs."

Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Organ Transplantation • Solid Tumor • Transplantation

Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial. (PubMed, Infect Dis Ther) - P2/3 | "WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19."

Journal • P2/3 data • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases