- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
Journal: Evaluating mAbs binding abilities to Omicron subvariant RBDs: implications for selecting effective mAb therapies. (Pubmed Central) - Apr 18, 2024
Our results indicated that the antibody LY-COV1404 maintained binding affinities across all studied systems, suggesting the resilience of certain antibodies against variant-induced immune escape, as seen with the mAb 1D1-Fab...These findings enhance our comprehension of the binding interactions between mAbs and RBDs, contributing to the understanding of immune escape mechanisms. They also lay the groundwork for the design and optimization of antiviral drugs and have significant implications for the development of treatments against current and future coronaviruses.
- |||||||||| bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases
Retrospective data, Review, Journal: Efficacy and safety of bamlanivimab in patients with COVID-19: A systematic review and meta-analysis. (Pubmed Central) - Apr 15, 2024
They also lay the groundwork for the design and optimization of antiviral drugs and have significant implications for the development of treatments against current and future coronaviruses. Although the results suggest the efficacy and safety of bamlanivimab in COVID-19 patients, further research is required to confirm the efficacy of this drug for the current circulating SARS-CoV-2 variants.
- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
mRNA delivery of epitope-specific monoclonal antibodies for treatment of viral infection (Exhibit Hall F1; Posterboard Number: 919) - Mar 29, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_893;
We generated mRNAs expressing two different mAbs, LY-CoV1404 (mRNA-1404) and 76E1 (mRNA-76E1), that target different SARS-CoV-2 epitopes and formulated them in LNPs...Following single mRNA-LNP administration (5ug and 15ug dose via intramuscular or subcutaneous route), serum antibodies remained detectable 5 weeks out. Our data indicate that mRNA is a promising platform for the delivery of therapeutic mAbs to treat human disease such as viral infections.
- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
Journal: Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies. (Pubmed Central) - Mar 19, 2024
Furthermore, we created a bispecific antibody by incorporating the scFv of bebtelovimab with our anti-S2 antibody, demonstrating significant restoration of effectiveness against bebtelovimab-resistant BQ.1.1 variants. This study highlights the potential of neutralizing bispecific antibodies, which combine existing less effective anti-RBD antibodies with anti-S2 antibodies, to revive the effectiveness of antibody therapeutics compromised by immune-evading variants.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: Evaluation of Physicians Prescribing of COVID-19 Guideline-Directed Outpatient Treatments in a Primary Care Walk-In Clinic. (Pubmed Central) - Mar 18, 2024
Nirmatrelvir-ritonavir was the most prescribed medication for the treatment of mild-to-moderate COVID-19, consistent with its position as first-line therapy and widespread accessibility. The study results will inform future educational opportunities, such as in-service presentations and handouts, that may improve the prescribing of outpatient treatment for mild-to-moderate COVID-19 moving forward.
- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly, Xevudy (sotrovimab) / GSK, National Institutes of Health, Vir Biotech, National Institute of Allergy and Infectious Diseases
Journal: SARS-CoV-2 evolution during prolonged infection in immunocompromised patients. (Pubmed Central) - Mar 14, 2024
All patients received remdesivir, but remdesivir-resistant substitutions were not detected...One model is that long-term viral persistence in infected individuals allows for viral evolution in response to host pressures, resulting in viruses more likely to replicate efficiently in humans. In this study, we characterize replication in several hospitalized and long-term infected individuals, documenting efficient pathways of viral evolution.
- |||||||||| bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases
Organizing Pneumonia With Surgical Pathology Positive for SARS-CoV2 a Year After Initial COVID-19 Diagnosis Despite Negative COVID-19 PCR From Nasal Swabs and Bronchial Alveolar Lavage in a Lymphopenic Cancer Patient (San Diego Convention Center, Area H (Hall H, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_4077;
He received monoclonal antibody, Bamlanivimab, with little improvement...Given symptoms, negative infectious work up including fungal markers and PET scan with new bilateral ground glass opacities (GGOs), he was started on prednisone 10mg daily for presumed long COVID-19...He tested COVID PCR negative multiple times and was treated for presumed pneumonia with Augmentin and Levofloxacin with minimal improvement in symptoms...While COVID PCR from a BAL has high sensitivity, the patient tested negative multiple times with the diagnosis ultimately made with immunohistochemical stains from biopsy. Steroids continue to be the treatment of choice for PCOP.
- |||||||||| Journal: Coronavirus Disease 2019 (COVID-19) in Heart Transplant Recipients and Anti-SARS-CoV-2 Monoclonal Antibodies: Experience, Lessons Learnt, and Future Challenges. (Pubmed Central) - Feb 9, 2024
We performed a retrospective chart review including adult HT recipients at Westchester Medical Center from January 1, 2020 to December 10, 2022, who received anti-SARS-CoV-2 monoclonal antibodies (mAbs) for treatment of mild-to-moderate COVID-19, and those who received tixagevimab/cilgavimab for preexposure prophylaxis...In this largest single-center study in this population, 42 adult HT recipients received casirivimab/imdevimab (36%), sotrovimab (31%), or bebtelovimab (29%) for treatment of mild-to-moderate COVID-19...Overall, the data suggests that HT recipients receiving mAbs have reduced rates of hospitalization, need for intensive care unit care, or death. Use of anti-SARS-CoV-2 mAbs in SOTRs is resource intensive and requires a programmatic team approach for optimal administration and to minimize any risk of disparities in their use.
- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
Journal: Allosteric Signal within the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein Mediated by a Class 3 Monoclonal Antibody Revealed through Molecular Dynamics Simulations and Protein Residue Networks. (Pubmed Central) - Feb 5, 2024
Simulations of explicitly solvated RBD of the BA.2.75 omicron subvariants were carried out both in the presence and in the absence of bebtelovimab, as a model example of class 3 monoclonal antibodies against the RBD of the SARS-CoV-2 spike protein...In terms of computational techniques, the communicability matrix could serve as a tool to visualize the effects of allostery, as the pairs of amino acids or secondary structures with high communicability could pinpoint the possible sites to transfer the allosteric signal. Additionally, the communicability gain/loss matrix could help elucidate the consequences of allosteric actions, which could be employed along with other allostery quantification techniques in some previous studies.
- |||||||||| Preclinical, Journal: In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1. (Pubmed Central) - Oct 28, 2023
At the current stage of the COVID-19 pandemic, the use of mAbs developed against early SARS-CoV-2 variants has little prospect. Specific antiviral drugs retain their activity, but further monitoring is needed to assess the risk of their efficacy being reduced and adjust recommendations for their use.
- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
Journal: Structural basis for broad neutralization of human antibody against Omicron sublineages and evasion by XBB variant. (Pubmed Central) - Oct 19, 2023
To date, almost all available therapeutic nAbs, including those authorized under Emergency Use Authorization nAbs that were previously clinically useful against early strains, have recently been found to be ineffective against newly emerging variants. In this study, we provide a comprehensive structural basis about how the Class 3 nAbs, including 1G11 in this study and noted LY-CoV1404, are evaded by the newly emerged SARS-CoV-2 variants.
- |||||||||| Evusheld (cilgavimab/tixagevimab) / AstraZeneca, bamlanivimab/etesevimab (LY-CoV555/LY-CoV016) / Eli Lilly, bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
Safety of Anti-SARS-CoV-2 Monoclonal Antibody Therapies: Clinical Characteristics and Outcomes of Adverse Drug Reactions (Monitor 11) - Sep 14, 2023 - Abstract #ACAAI2023ACAAI_860;
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.
- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
Post (In-Person) - Sep 4, 2023 - Abstract #CAP2023CAP_266;
One patient had received bebtelovimab prior to the resolution of symptoms...Neutrophils were noted to be clustered within vessels in both cases and often adhered to a reactive-appearing endothelium, without migration through the vessel wall (Figure 1.107, B). Immunohistochemistry was negative for SARS-CoV-2 spike and nucleocapsid proteins, supporting a postulated aberrant immune response rather than the continued presence of active SARS-CoV-2 mediating the presence of this postacute inflammatory response.
- |||||||||| bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases
Journal: Long COVID After Bamlanivimab Treatment. (Pubmed Central) - Aug 31, 2023
P2/3
Long COVID occurred despite early, effective monoclonal antibody therapy and was associated with smoking, female sex, and non-Hispanic ethnicity, but not viral burden. The strong association between symptoms 22-28 days after treatment and long COVID suggests that processes of long COVID start early and may need early intervention.
- |||||||||| bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases, Xevudy (sotrovimab) / GSK, National Institutes of Health, Vir Biotech, National Institute of Allergy and Infectious Diseases
Trial completion: TICO: ACTIV-3: Therapeutics for Inpatients With COVID-19 (clinicaltrials.gov) - Aug 25, 2023
P3, N=2753, Completed,
The strong association between symptoms 22-28 days after treatment and long COVID suggests that processes of long COVID start early and may need early intervention. Active, not recruiting --> Completed
- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
Journal: Digital PCR Discriminates between SARS-CoV-2 Omicron Variants and Immune Escape Mutations. (Pubmed Central) - Aug 21, 2023
For example, bebtelovimab is no longer authorized for emergency use in the United States due to the increased prevalence of antibody-resistant BQ.1, BQ.1.1, and XBB Omicron subvariants...In this study, we demonstrate the proof of concept that dPCR can be used to type lineage defining and monoclonal antibody resistance-associated mutations in saliva specimens. These findings show that digital PCR could be used as a personalized diagnostic tool to guide individual patient treatment.
- |||||||||| bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases, Darzalex (daratumumab) / J&J
Journal: Clinical Features and Risk Stratification of Multiple Myeloma Patients with COVID-19. (Pubmed Central) - Jul 29, 2023
The neutralizing antibody decreases overall mortality. Evidence from the current study and previous publications suggest that testing of neutralizing antibody post-SARS-CoV-2 vaccination in MM patients may be needed in reducing COVID-19 risk.
- |||||||||| bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases
Trial completion: ACTIV-2: A Study for Outpatients With COVID-19 (clinicaltrials.gov) - Jul 27, 2023
P2/3, N=4044, Completed,
Evidence from the current study and previous publications suggest that testing of neutralizing antibody post-SARS-CoV-2 vaccination in MM patients may be needed in reducing COVID-19 risk. Active, not recruiting --> Completed
- |||||||||| Enrollment change, Trial termination: UPMC OPTIMISE-C19 Trial, a COVID-19 Study (clinicaltrials.gov) - Jun 15, 2023
P4, N=4571, Terminated,
Because of significant drug-drug interactions between nirmatrelvir-ritonavir and immunosuppressive agents as well as N=23858 --> 4571 | Completed --> Terminated; Emergency Use Authorizations for monoclonal antibodies withdrawn
- |||||||||| Journal: SABRes: in silico detection of drug resistance conferring mutations in subpopulations of SARS-CoV-2 genomes. (Pubmed Central) - May 13, 2023
These genomes accounted for a 1.18% prevalence of resistant isolates discovered by SABRes, including 80 genomes with resistance conferring mutations found in viral subpopulations. Timely recognition of these mutations within subpopulations is critical as these mutations can provide an advantage under selective pressure and presents an important step forward in our ability to monitor SARS-CoV-2 drug resistance.
- |||||||||| bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases, bamlanivimab/etesevimab (LY-CoV555/LY-CoV016) / Eli Lilly, etesevimab (JS016) / Chinese Academy of Sciences, Shanghai Junshi Biosci, Eli Lilly
Trial completion, Trial completion date, Trial primary completion date: BLAZE-1: A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (clinicaltrials.gov) - May 12, 2023
P2/3, N=3307, Completed,
Timely recognition of these mutations within subpopulations is critical as these mutations can provide an advantage under selective pressure and presents an important step forward in our ability to monitor SARS-CoV-2 drug resistance. Recruiting --> Completed | Trial completion date: Oct 2023 --> Feb 2023 | Trial primary completion date: Oct 2023 --> Feb 2023
- |||||||||| Clinical, Review, Journal: Efficacy and Safety of Anti-SARS-CoV-2 Monoclonal Antibodies: An Updated Review. (Pubmed Central) - May 6, 2023
Monoclonal antibodies (mAbs) had received emergency use authorization for mild-to-moderate coronavirus disease 2019 (COVID-19) or for prophylaxis against COVID-19, including casirivimab plus imdevimab (C+I), bamlanivimab plus etesevimab (B+E), tixagevimab plus cilgavimab (T+CG), and sotrovimab (S) and bebtelovimab (BEB)...The response was better in the seronegative patients. Most of these studies were conducted in unvaccinated individuals and against Alpha, Gamma, and Delta variants.
- |||||||||| REGEN-COV (casirivimab/imdevimab) / Regeneron, Roche, bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases
Journal: Post-Acute SARS-CoV-2 Symptoms are Fewer, Less Intense Over Time in People Treated with Mono-Clonal Antibodies for Acute Infection. (Pubmed Central) - May 1, 2023
mAb treated participants had reduced symptom burden and consistently reported fewer symptoms than non-mAb at all time points despite less time since acute illness. Both groups reported a statistically significant decrease in symptoms by 6-month visit with no statistically significant differences between them at follow-up.
- |||||||||| bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly
Journal: Bilateral Lung Transplantation With Donor Positive for COVID-19 Infection on Bronchoalveolar Lavage: A Case Report. (Pubmed Central) - May 1, 2023
Bebtelovimab was given post-transplant day 1 because the recipient remained seronegative to COVID-19...She was seen in the clinic 2 months post transplant and is ambulatory without supplemental oxygen requirements. To our knowledge, this represents the first reported successful case of lung transplant with a donor positive for COVID-19 on lower respiratory tract sampling.
- |||||||||| Review, Journal: Antiviral Treatment of Coronavirus Disease-2019 Pneumonia. (Pubmed Central) - Apr 26, 2023
Following an emphasis on inpatient treatment of COVID-19 during the early pandemic, several therapeutic options were developed for outpatients with COVID-19. Additional clinical trials and real-world studies are needed to keep pace with the evolving pandemic.
- |||||||||| bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases, Xevudy (sotrovimab) / GSK, National Institutes of Health, Vir Biotech, National Institute of Allergy and Infectious Diseases
Enrollment change, Trial termination: CATCO-NOS: Treatment of Nosocomial COVID-19 (clinicaltrials.gov) - Apr 19, 2023
P4, N=46, Terminated,
Our HCT cohort patients had less hospitalization rate compared with HM cohort patients. N=648 --> 46 | Suspended --> Terminated; Equipoise requirement no longer met.
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