REGEN-COV (casirivimab/imdevimab) / Regeneron, Roche - LARVOL DELTA

Assessing treatment efficacy for interval-censored endpoints using multistate semi-Markov models fit to multiple data streams. (PubMed, Biostatistics) - "Our motivating application is the REGEN-2069 trial, which investigated the protective efficacy (PE) of the monoclonal antibody combination REGEN-COV against SARS-CoV-2 when administered prophylactically to individuals in households at high risk of secondary transmission...Our algorithm for fitting semi-Markov models to interval-censored data employs a Monte Carlo expectation-maximization algorithm combined with importance sampling to efficiently address the intractability of the marginal likelihood when data are intermittently observed. Our algorithm provides substantial computational improvements over existing methods and allows us to fit semi-parametric models despite complex coarsening of the data."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Clinical efficacy of casirivimab and imdevimab in preventing COVID-19 in the Omicron BA.5 subvariant epidemic: a retrospective study. (PubMed, J Pharm Health Care Sci) - "CAS + IMD may be effective for post-exposure prophylaxis of COVID-19 during the Omicron BA.5 subvariant epidemic. However, prudent clinical use should consider the circulating variant profile. Further research is warranted to validate CAS + IMD's role in COVID-19 post-exposure prophylaxis."

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

COVID-19 Study to Evaluate Safety, Tolerability, and Efficacy of REGN14256+Imdevimab for the Treatment of COVID-19 Adult and Adolescent Patients Without Risk Factors for Progression to Severe Disease (clinicaltrials.gov) - P1/2 | N=25 | Terminated | Sponsor: Regeneron Pharmaceuticals | Phase classification: P1 ➔ P1/2

Phase classification • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

COVID-19 Administration of Single-Dose Subcutaneous Anti- Spike(s) SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Participants Under 12 Years of Age (clinicaltrials.gov) - P2 | N=7 | Terminated | Sponsor: Regeneron Pharmaceuticals | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases

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

COVID-19 Study of Pharmacokinetics, Safety, Tolerability, and Efficacy of Intravenous Anti-Spike(s) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) for the Treatment of Pediatric Patients Hospitalized Due to COVID-19 (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: Regeneron Pharmaceuticals | Phase classification: P1b ➔ P1

Phase classification • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases

Domain-Specific Impacts of Spike Protein Mutations on Infectivity and Antibody Escape in SARS-CoV-2 Omicron BA.1. (PubMed, J Microbiol Biotechnol) - "Despite lower infectivity compared to Delta, BA.1 pseudoviruses harboring RBD mutations exhibited robust resistance to neutralizing monoclonal antibodies, including casirivimab and imdevimab, with IC50 values exceeding assay limits. These findings indicate that Omicron BA.1's rapid global spread is driven by enhanced immune evasion conferred by RBD mutations, even at the expense of viral entry efficiency. Our domain-specific analysis underscores the critical roles of spike protein mutations in shaping Omicron BA.1's transmissibility and antibody escape, informing strategies for therapeutic and vaccine development."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Prolonged COVID-19 infection in a patient with B-cell acute lymphoblastic leukemia maintained on convalescent plasma until recovery with monoclonal antibodies. (PubMed, Lab Med) - "This case illustrates the limitations of CCP in patients with prolonged SARS-CoV-2 infection and highlights the effectiveness of mAbs in achieving viral clearance in severely immunocompromised hosts. It supports targeted use of mAb therapy in select high-risk populations and reinforces the importance of specific passive immunotherapy strategies (when available) for the management of viremia in immunodeficient patients."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Efficacy and safety of casirivimab/imdevimab (REGEN-COV) in pregnant individuals with COVID-19: Literature review and insights from the COVID-19 International Drug Pregnancy Registry. (PubMed, Obstet Med) - "The drugs are well-tolerated, and there is no compelling evidence of adverse maternal or neonatal outcomes. The results from the COVID-PR study are consistent with those of the broader literature."

Journal • Infectious Disease • Novel Coronavirus Disease • Obstetrics • 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

A Fatal Complication After Prophylactic Anticoagulation for COVID-19 in a Lung Transplant Recipient (ATS 2025) - "We describe a lung transplant recipient who developed RSH following prophylactic enoxaparin administration for COVID-19 treatment. Description: 78-year-old man with a significant medical history including bilateral lung transplantation two years prior due to chronic obstructive pulmonary disease (COPD), maintained on an immunosuppressive regimen of tacrolimus, mycophenolate mofetil, and prednisone presented to the emergency department with fever, severe headaches, and myalgias...He was initiated on a treatment regimen including high-dose steroids, remdesivir, monoclonal antibodies (casirivimab and imdevimab), and apixaban for thromboembolism prophylaxis...In the context of COVID-19, where anticoagulation is frequently indicated, awareness of RSH's potential is essential. While most RSH cases can be managed conservatively or via angiographic intervention, this case highlights the increased mortality risk associated with RSH in patients suffering from COVID-19."

Clinical • Cardiovascular • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Pneumonia • Pulmonary Disease • Respiratory Diseases • Transplantation

Unraveling the Dynamic Interplay of SARS-CoV-2 Neutralizing Monoclonal Antibodies and Host Immunity in Hospitalized Patients with COVID-19 (IMMUNOLOGY 2025) - "Description Passive administration of SARS-CoV-2 neutralizing monoclonal antibodies, such as the CAS+IMD (REGEN-COV®, Ronapreve, REGN-COV2) antibody cocktail, benefits viral load, mortality rate, and clinical course in COVID-19 patients...Additionally, CAS+IMD did not impair the magnitude or quality of host T cell immunity against the SARS-CoV-2 spike protein. These findings suggest that SARS-CoV-2 neutralizing antibodies can rapidly resolve inflammatory responses, reducing the need for systemic steroids, without compromising cellular antiviral immunity.Keywords: Animals Human; Infections Viral; Molecules Antibodies Cytokines; Processes Inflammation"

Clinical • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

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

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

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

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

Monoclonal Antibodies in Prevention and Early Treatment of COVID-19 in Lung Transplant Recipients: A Systematic Review and Perspective on the Role of Monoclonal Antibodies in the Future. (PubMed, Transpl Int) - "Moreover, mAb therapy appeared safe and could be a viable option against other pathogens, a route that warrants further investigation. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=382133, identifier CRD42022382133."

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

Medical Herbs Inhibit Inflammation Directing T Cells to Kill the COVID-19 Virus (COVID) (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: All Natural Medicine Clinic, LLC | Trial completion date: Mar 2023 ➔ May 2027 | Trial primary completion date: Dec 2022 ➔ Dec 2026

Trial completion date • Trial primary completion date • Infectious Disease • Inflammation • Novel Coronavirus Disease • CD4 • CD8 • CRP

Chugai Announces Consolidated 2024 Full Year Results and Forecasts for 2025 (Chugai Press Release) - "In the specialty field, sales decreased by 28.3% compared with previous year, mainly due to the completion of supply of Ronapreve to the government, despite that our new product Vabysmo grew and our mainstay products Hemlibra and Actemra performed well. Overseas sales were ¥536.8 billion (+ ¥120.3 billion, +28.9%, YoY), driven by a substantial increase in exports of Hemlibra to Roche. Other revenue increased by 26.2% mainly due to increase in one-time income, etc., in addition to the increase in income related to Hemlibra...Overseas sales are expected to be ¥555.5 billion (+ ¥18.7 billion, +3.5%, YoY) due to growth in sales of Hemlibra...and NEMLUVIO, despite decrease in Actemra."

Commercial • Sales • Age-related Macular Degeneration • Atopic Dermatitis • Dermatitis • Diabetic Macular Edema • Hemophilia A • Idiopathic Arthritis • Inflammatory Arthritis • Macular Degeneration • Macular Edema • Novel Coronavirus Disease • Prurigo Nodularis • Pruritus • Retinal Vein Occlusion • Rheumatoid Arthritis • Scleroderma • Systemic Sclerosis • Vasculitis • Wet Age-related Macular Degeneration

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

Monoclonal antibodies against the spike protein alter the endogenous humoral response to SARS-CoV-2 vaccination and infection. (PubMed, Sci Transl Med) - "Here, we describe the impact of administration of an antibody combination, casirivimab plus imdevimab (CAS+IMD), on immune responses to subsequent SARS-CoV-2 vaccination in humans, nonhuman primates, and mice...Moreover, by assessing the antiviral immune response in SARS-CoV-2-infected individuals treated therapeutically with CAS+IMD, we demonstrated alteration of antiviral humoral immunity in those who had received mAb therapy, but only in those individuals who had yet to start mounting their natural immune response at the time of mAb treatment. Together, these data demonstrate that antiviral mAbs can alter endogenous humoral immunity during vaccination or infection."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

COVIC-19: Early High-Titre Convalescent Plasma in Clinically Vulnerable Individuals With Mild COVID-19 (clinicaltrials.gov) - P3 | N=120 | Terminated | Sponsor: Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen | N=680 ➔ 120 | Recruiting ➔ Terminated; Due to the significant decline in the number of newly diagnosed infections and the difficulties in opening new centers in the outgoing pandemic, recruitment declined. The Data Safety Monitoring Board recommended to stop the trial.

Enrollment change • Trial termination • Infectious Disease • Neutropenia • Novel Coronavirus Disease • BCL2

Assessing the safety and pharmacokinetics of casirivimab and imdevimab (CAS+IMD) in a cohort of pregnant outpatients with COVID-19: results from an adaptive, multicentre, randomised, double-blind, phase 1/2/3 study. (PubMed, BMJ Open) - P3 | "CAS+IMD treatment of pregnant outpatients with COVID-19 showed similar safety, clinical outcomes and pharmacokinetic profiles to that observed in non-pregnant adults. There was no evidence of an impact on developmental outcomes in infants ≤1 year of age."

Clinical • Journal • P1/2 data • PK/PD data • Immunology • Infectious Disease • Novel Coronavirus Disease