Regkirona (regdanvimab) / Celltrion - LARVOL DELTA

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

Current status and clinical outcomes of pharmacotherapies according to SARS-CoV-2 mutations in patients with mild-to-moderate COVID-19: a retrospective single center study. (PubMed, BMC Infect Dis) - "Regdanvimab was primarily used during the ancestral strain period, regdanvimab plus corticosteroids during the Delta variant period, and remdesivir during the Omicron variant period. The rate of death or disease aggravation was highest in the Delta variant, followed by the Omicron variant and the ancestral strain."

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

Monoclonal Antibody Therapies Against SARS-CoV-2: Promises and Realities. (PubMed, Curr Top Microbiol Immunol) - "Unfortunately, the Omicron variant of concern has completely reset all achievements so far in mAb therapy for COVID-19. Despite the intrinsic limitations of this strategy, future developments such as respiratory delivery of further engineered mAb cocktails could lead to improved outcomes."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A review on the current approaches and perspectives of Covid-19 treatment. (PubMed, Pol Merkur Lekarski) - "Currently, 11 antiviral drugs (Tixagevimab/Cilgavimab, Regdanvimab, Casirivimab/Imdevimab, Sotrovimab, Nirmatrelvir/Ritonavir, Remdesivir, Molnupiravir, Baricitinib, Anakinra, Tocilizumab, Vilobelimab) have been approved or conditionally approved by the European Medicines Agency and/or by the Food and Drug Administration and are available on the pharmaceutical market. The article brief l y describes the current epidemiological situation regarding COVID-19 and the currently used vaccines. Moreover, the paper outlines currently used and researched potential drugs in the pharmacotherapy of this disease."

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

Effectiveness of regdanvimab on clinical outcomes in COVID-19 infected patients on hemodialysis (ERA-EDTA 2024) - "Of these, 77 (33.5%) were treated with regdanvimab alone or in combination with dexamethasone or remdesivir during hospitalization (regdanvimab group), and 153 (66.5%) did not treat with regdanvimab (non- regdanvimab group). Regdanvimab administration is beneficial in improving prognosis in hospitalized COVID-19 patients on HD. Considering the vulnerability of ESKD patients to infection, regdanvimab may be considered as a therapeutic option in COVID-19 patients on HD."

Clinical • Clinical data • Infectious Disease • Nephrology • Novel Coronavirus Disease • Oncology • Renal Disease • Respiratory Diseases

Treatment of Patients After Lung Transplantation With Covid Infection During Long-Term Follow-Up. (PubMed, Transplant Proc) - "Fifteen post-lung transplantation patients with current COVID-19 infection were treated with antibodies such as tocilizumab, casirivimab, imdevimab, and regdanvimab. Antiviral agents, like remdesivir, were employed in the remaining 4 cases (27%), and adjunctive therapies, such as corticosteroids and anticoagulants, were used selectively. All treated patients survived the infection without complications; the treatment proved effective and safe."

Journal • Fatigue • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Transplantation • IL6

Effect of Regdanvimab on Mortality in Patients Infected with SARS-CoV-2 Delta Variants: A Propensity Score-Matched Cohort Study. (PubMed, Infect Dis Ther) - "We showed that regdanvimab reduced the exacerbation rates of conditions and mortality in patients with the COVID-19 delta variant infection. Thus, it is recommended to streamline the drug approval system during epidemics of new variant viruses to improve the availability and usage of therapeutics for patients. To facilitate this, relevant institutional support is required."

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

Effectiveness of regdanvimab on mortality in COVID-19 infected patients on hemodialysis. (PubMed, Kidney Res Clin Pract) - "We conducted an observational retrospective study in 230 COVID-19-infected patients on HD, of whom 77 (33.5%) were administered regdanvimab alone or in combination with dexamethasone or remdesivir during hospitalization (regdanvimab group) and 153 patients (66.5%) were not (no regdanvimab group). Regdanvimab administration is beneficial in improving prognosis in hospitalized COVID-19 patients on HD. Considering the vulnerability to infection and high mortality of ESRD patients, regdanvimab may be considered as a therapeutic option in COVID-19 patients on HD."

Journal • Chronic Kidney Disease • Infectious Disease • Nephrology • Novel Coronavirus Disease • Oncology • Renal 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

Clinical outcomes of mild to moderate coronavirus disease 2019 patients treated with Regdanvimab in delta-variant outbreak: Retrospective cohort study. (PubMed, Medicine (Baltimore)) - "Patients treated with regdanvimab 4 days after symptom onset showed a favorable prognosis (aHR, 0.26; 95% CI, 0.26-0.91). We found that the high-risk mild to moderate COVID-19 patients treated with regdanvimab showed similar disease progression in delta-variant patients and pre-delta variants; however, we need to be more closely observed delta-variant patients than those in the pre-delta group despite regdanvimab treatment due to rapid disease aggravation."

Clinical data • Journal • Retrospective data • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Real-world clinical effectiveness of Tixagevimab/Cilgavimab and Regdanvimab monoclonal antibodies for COVID-19 treatment in Omicron variant-dominant period. (PubMed, Front Immunol) - P4 | "In the group of intravenous Regdanvimab, a significant increase in the level of nAbs to the Wuhan variant was detected immediately after the drug administration, while no increase in nAbs to different Omicron sublineages was observed. https://clinicaltrials.gov/, identifier NCT05982704."

Journal • Real-world • Real-world evidence • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Clinical trials approved by Aifa for Covid-19: report of the main results to fill the unmet medical need. (PubMed, Recenti Prog Med) - "The methods of early access to therapy have allowed an alternative to patients who are not eligible for the ongoing trials. The challenge that the scientific community has faced has strengthened the culture of evidence-based medicine."

Journal • Infectious Disease • Novel Coronavirus Disease

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, Vaccines (Basel)) - "We studied the in vitro efficacy of mAbs Tixagevimab + Cilgavimab (Evusheld), Sotrovimab, Regdanvimab, Casirivimab + Imdevimab (Ronapreve), and Bebtelovimab, as well as the specific antiviral drugs Remdesivir, Molnupiravir, and Nirmatrelvir, against these genetic lines. 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."

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

Safety and Effectiveness of Regdanvimab for COVID-19 Treatment: A Phase 4 Post-marketing Surveillance Study Conducted in South Korea. (PubMed, Infect Dis Ther) - "This large-scale PMS study demonstrated that regdanvimab was effective against COVID-19 progression and had an acceptable safety profile when used in real-world clinical practice."

Journal • P4 data • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19 (clinicaltrials.gov) - P4 | N=82 | Active, not recruiting | Sponsor: City Clinical Hospital No.52 of Moscow Healthcare Department

New P4 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

THE USE OF REGDANVIMAB FOR THE PREVENTION OF SEVERE COVID-19 IN PATIENTS ON HEMODIALYSIS (ERA-EDTA 2023) - "The results of our study showed the efficacy of Regdanvimab to prevent the severe disease of COVID-19 in high-risk patients during the period of rising morbidity."

Clinical • Cough • Infectious Disease • Novel Coronavirus Disease • Pain • Respiratory Diseases

Effectiveness of regdanvimab treatment for SARS-CoV-2 delta variant, which exhibited decreased in vitro activity: a nationwide real-world multicenter cohort study. (PubMed, Front Cell Infect Microbiol) - "Regdanvimab treatment effectively reduced progression to severe disease in the overall study population, but did not show significant effectiveness in the delta-confirmed patients. The effectiveness of dose increment of monoclonal antibody agents should be evaluated for variant strains exhibiting reduced susceptibility."

Journal • Preclinical • Real-world • Real-world evidence • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • KEAP1

Correction to: A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019. (PubMed, Open Forum Infect Dis) - "[This corrects the article DOI: 10.1093/ofid/ofac406.]."

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

CLINICAL CHARACTERISTICS AND OUTCOMES OF PERI-HSCT COVID-19 INFECTION IN CHILDREN WITH INBORN ERRORS OF IMMUNITY (IEI) (EBMT 2023) - "All patients received Fludarabine-Treosulfan-Thiotepa and Alemtuzumab (n=4) or ATG+Rituximab (n=3)...Five patients were on immunosuppression (steroids and/or cyclosporine) during the course of their illness (Figure 1). All patients received remdesivir (1 patient received 2 courses) and 6 patients received COVID-19 directed monoclonal antibody (Sotrovimab=5; Regdanvimab=1)... In countries where restrictions have been relaxed, leading to relative endemicity of the virus, concomitant SARS-CoV-2 infection in children embarking on HSCT or with significant immunosuppression is expected to become commonplace, highlighting the importance of novel strategies. Our small cohort shows a favourable outcome in paediatric patients with pre-HSCT and persistent COVID-19 infection in children with IEI."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Primary Immunodeficiency • Rare Diseases • Respiratory Diseases • Transplantation • CD19 • RAG1

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

Antiviral drugs block replication of highly immune-evasive Omicron subvariants ex vivo, but fail to reduce tissue inflammation. (PubMed, Antiviral Res) - "We found that the antiviral drugs Molnupiravir, Nirmatrelvir and Remdesivir efficiently inhibit BA.4/BA.5, BF.7 and BQ.1.1 replication. In contrast, only the monoclonal antibody Cilgavimab exerted an inhibitory effect, while Tixagevimab, Regdanvimab and Sotrovimab lost their efficacy against BA.4/BA.5...Of note, all tested monoclonal antibodies had no neutralizing activity during infection by BF.7 and BQ.1.1 variants. Our results suggest that despite a marked reduction of viral replication, potent antiviral drugs fail to reduce tissue levels of inflammatory compounds such as C3, which can still result in tissue destruction."

Journal • Preclinical • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Efficacy and safety of regdanvimab in patients with mild to moderate COVID-19: A rapid review and meta-analysis. (PubMed, Br J Clin Pharmacol) - "Regdanvimab was not effective in reducing mortality and hospital admission rate in patients with mild to moderate COVID-19, but it was effective in improving other efficacy outcomes. Further research is needed to confirm these findings."

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

Regdanvimab for patients with mild-to-moderate COVID-19: a retrospective cohort study and subgroup analysis of patients with the Delta variant. (PubMed, Int J Infect Dis) - "Regdanvimab demonstrated clinical efficacy in the overall cohort and may provide a clinical benefit for patients with mild-to-moderate COVID-19, infected with the Delta variant."

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

Health Technology Assessment (HTA) Methods for Monoclonal Antibodies for Treatment and Prevention of COVID-19 (ISPOR-EU 2022) - "Of nine mAbs available for treatment and prevention of COVID-19, four are the subject of HTA: Casirivimab & Imdevimab: HAS (published; early access granted), CADTH (published; unable to make a decision), NICE (in progress), G-BA (in progress) Lenzilumab: NICE (in progress) Sotrovimab: HAS (published; opinion in favor of reimbursement), CADTH (published; no decision) NICE (in progress), G-BA (in progress) Tocilizumab: NICE (in progress), CADTH (published; no decision) No HTAs were identified for the remaining five mAbs: bebtelovimab, bamlanivimab & etesevimab, regdanvimab, sarilumab, and tixagevimab & cilgavimab. Agencies are applying HTA procedures to COVID-19 technologies. Assessments, particularly for COVID-19 mAbs, will face challenges. Differing trial designs, definitions and outcomes, and a lack of standard-of-care treatments early in the pandemic may render estimates of comparative effectiveness invalid."

Infectious Disease • Novel Coronavirus Disease