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

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

Ensitrelvir (Xocova) for post-exposure prophylaxis of COVID-19. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Effect of Early Administration of Casirivimab and Imdevimab in Hospitalized Patients with COVID-19: A Post Hoc Analysis. (PubMed, Infect Drug Resist) - "These differences were most notable in those aged 50-70 years (OR: 0.24; 95% CI, 0.05-0.70; P = 0.0219). Early monoclonal antibody treatment is associated with better outcomes in hospitalized patients with severe COVID-19."

Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease

Drug-induced thrombocytopenia after SARS CoV-2 monoclonal antibody administration treated with plasma exchange. (PubMed, Transfus Apher Sci) - "He had a history of atrial fibrillation for which he was taking rivaroxaban...A diagnosis of drug-induced thrombocytopenia due to REGEN-COV was made and despite platelet transfusions, intravenous immunoglobulin 2 g/kg, and dexamethasone 40 mg daily, his platelet count stayed at < 1 or 1 × 109/L...The patient was treated for SARS-CoV-2 by other means and discharged on day 22. Plasma exchange should be considered when rapid removal of therapeutic monoclonal antibody is warranted due to life-threatening side effects."

Journal • Atrial Fibrillation • Cardiovascular • Fatigue • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

Cardiovascular Risks of COVID-19 Therapeutics: Integrated Analysis of FAERS, Electronic Health Records, and Transcriptomics. (PubMed, Pharmaceuticals (Basel)) - " Comparative analysis of three approved COVID-19 therapies revealed that COVID-19 patients treated with remdesivir had a higher risk of cardiovascular events than those treated with Paxlovid or REGEN-COV. Pathway enrichment analysis on transcriptomic data revealed that the "cGMP-PKG signaling pathway", "dilated cardiomyopathy", and "calcium signaling pathway" were enriched among genes up-regulated by remdesivir exposure. In summary, our integrated analysis of pharmacovigilance, EHR, and transcriptomic data provides convergent evidence for associations between remdesivir and cardiovascular ADEs and offers biological context into these associations."

Journal • Cardiomyopathy • Cardiovascular • Hypotension • Infectious Disease • Novel Coronavirus Disease

RECOVERY: Randomised Evaluation of COVID-19 Therapy (clinicaltrials.gov) - P3 | N=70000 | Recruiting | Sponsor: University of Oxford | Trial completion date: Jun 2036 ➔ Sep 2038 | Trial primary completion date: Jun 2026 ➔ Sep 2028

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

A Real-World Study of Anti-SARS-CoV-2 Monoclonal Antibodies in Prophylaxis and Curative of Covid-19 (COVIMAB) (clinicaltrials.gov) - P=N/A | N=4235 | Completed | Sponsor: Assistance Publique - Hôpitaux de Paris | Recruiting ➔ Completed

Real-world evidence • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effect of background asthma and allergic conditions on prophylaxis and treatment of COVID-19 infection. (PubMed, Ann Allergy Asthma Immunol) - "In outpatients with COVID-19, a history of allergic disease was associated with heightened susceptibility to infection but better clinical outcomes (hospitalization/death). CAS+IMD improved clinical outcomes in those with established infection and prevented infection in both allergic and non-allergic participants."

Journal • Allergic Rhinitis • Allergy • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Insights into the structural differences between homo- and heterodimers enriched from a cocktail of monoclonal antibodies against SARS-CoV-2. (PubMed, Sci Rep) - "Based on this study, the extent of covalent modification and distribution of the dimerization interface (Fab-Fab, Fab-Fc, and Fc-Fc) was observed to be highly correlated with potency for the REGEN-COV® combination. Overall, we propose that a comprehensive and well-executed study which leverages deep biophysical, biochemical, and functional analyses to compare heteromeric aggregates, with unknown properties, to related homodimer aggregates, with known properties, may represent an effective non-clinical based strategy to investigate attribute-function relationships in antibody dimers and potentially support mitigating risks incurred by heterodimers in co-formulated mAb samples."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

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

REGEN-COV as the First Line of Defense-A Single-Centre Experience. (PubMed, Life (Basel)) - "Our study showed that in high-risk patients, with specific variants of SARS-CoV-2, the use of REGEN-COV was associated with a lower risk of hospitalization, and it was associated with better disease outcomes. One of the limitations of this study was the variant-specific effectiveness of REGEN-COV, which may limit generalizability."

Journal • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

TURN-COVID Biobank: The Dutch Cohort Study for the Evaluation of the Use of Neutralizing Monoclonal Antibodies and Other Antiviral Agents Against SARS-CoV-2 (clinicaltrials.gov) - P=N/A | N=1178 | Completed | Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Sep 2025 | Trial primary completion date: Jun 2024 ➔ Sep 2025

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

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