Safety and Effectiveness of Regdanvimab for COVID-19 Treatment: A Phase 4 Post-marketing Surveillance Study Conducted in South Korea DOI Creative Commons
Ji Yeon Lee, Seon Hee Bu, Eun-Hyang Song

et al.

Infectious Diseases and Therapy, Journal Year: 2023, Volume and Issue: 12(10), P. 2417 - 2435

Published: Oct. 1, 2023

Regdanvimab, a neutralising monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), received approval for the treatment of disease 2019 (COVID-19) in South Korea 2021. The Ministry Food and Drug Safety mandate that new medications be re-examined safety effectiveness post-approval at least 3000 individuals. This post-marketing surveillance (PMS) study was used to evaluate regdanvimab real-world clinical care. prospective, multicentre, phase 4 PMS conducted between February 2021 March 2022 Korea. Eligible patients were aged ≥ 18 years with confirmed mild COVID-19 high risk progression or moderate COVID-19. Patients hospitalised treated (40 mg/kg, day 1) then monitored until discharge, follow-up call on 28. Adverse events (AEs) documented, rate measure effectiveness. Of 3123 infection identified, 3036 eligible inclusion. Approximately 80% 5% diagnosed during delta- omicron-dominant periods, respectively. Median (range) age 57 (18–95) years, 50.6% male. severity assessed before treatment, high-risk 1030 (33.9%) 2006 (66.1%) patients, AEs adverse drug reactions (ADRs) experienced by 684 (22.5%) 363 (12.0%) most common ADR increased liver function test (n = 62, 2.0%). Nine (0.3%) discontinued due ADRs. Overall, 378 (12.5%) after infusion, extended hospitalisation/re-admission 300, 9.9%) as reason. Supplemental oxygen required 282 (9.3%) patients. Ten intensive care monitoring 3 (0.1%) died large-scale demonstrated effective had an acceptable profile when practice.

Language: Английский

Ursodeoxycholic acid does not affect the clinical outcome of SARS‐CoV‐2 infection: A retrospective study of propensity score‐matched cohorts DOI Creative Commons
Giuseppe Marrone, Marcello Covino, Giuseppe Merra

et al.

Liver International, Journal Year: 2023, Volume and Issue: 44(1), P. 83 - 92

Published: Sept. 21, 2023

Abstract Background Ursodeoxycholic acid (UDCA) has been recently proposed as a modulator of angiotensin‐converting enzyme 2 (ACE2) receptor expression, with potential effects on COVID‐19. Aim and Study Design We retrospectively evaluated the clinical course outcome subjects taking UDCA admitted to hospital for COVID‐19 compared matched infected subjects. Differences regarding severity disease between treated non‐treated were assessed. The Kaplan–Meier survival analysis log‐rank test used evaluate effect all‐cause intra‐hospital mortality. Results Among 6444 confirmed emergency department (ED) from 1 March 2020 31 December 2022, 109 UDCA. After matching 629 included in study: 521 no group 108 group. In our cohort, 144 (22.9%) died, 118 (22.6%) no‐UDCA 26 (24.1%) showed significant difference groups. univariate regression analysis, presence pneumonia, National Early Warning Score (NEWS) score, Charlson Comorbidity Index (CCI) independent predictors death. At multivariate Cox age, NEWS, pneumonia CCI index treatment was not predictor both regressions. Conclusions does appear have Specially designed prospective studies are needed efficacy preventing infection severe disease.

Language: Английский

Citations

12
Efficacy of Preexposure Prophylaxis with Monoclonal Antibody Tixagevimab-Cilgavimab against Emerging SARS-CoV-2 Resistant Variants in Patients with Chronic Lymphocytic Leukemia DOI Creative Commons

Ohad Benjamini,

Tamar Tadmor,

Abraham Avigdor

et al.

Acta Haematologica, Journal Year: 2024, Volume and Issue: 147(6), P. 634 - 645

Published: March 12, 2024

Preexposure prophylaxis with monoclonal antibodies (mAbs) was developed in addition to COVID-19 vaccine for immunocompromised and those insufficient immune response, among them patients CLL. Omicron variant its sublineages evolved mutations that escape mAbs neutralizing effect, yet the extent of which not studied.

Language: Английский

Citations

4
Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1 DOI Creative Commons
Zhou Tong, Jianyu Tong, Wenwen Lei

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(6), P. 114338 - 114338

Published: June 1, 2024

The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in study. It could effectively restore neutralizing activity of bsAb when any its single is escaped by variants. This synergy primarily attributed to binding angle receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking promoting cryptic epitope exposure that classical cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. study not only shifts paradigm understanding interactions but paves way for developing more effective against rapidly mutating SARS-CoV-2, Dia-19 already showing promise like BA.2.86, EG.5.1, JN.1.

Language: Английский

Citations

4
Development of potent pan‐coronavirus fusion inhibitors with a new design strategy DOI Creative Commons
Yuanmei Zhu,

Zhongcai Gao,

Xiaoli Feng

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 28, 2024

Abstract Development of potent and broad‐spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains one the top priorities, especially in cases emergence mutant viruses inability current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion‐inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, report its design strategy preclinical data. First, surprisingly found that IPB29 with rigid linker between peptide sequence lipid molecule had greatly improved α‐helical structure antiviral activity. Second, potently inhibited large panel SARS‐CoV‐2 variants including previously circulating viruses, such as Omicron XBB.5.1 EG.5.1. Third, could also cross‐neutralize bat‐ pangolin‐isolated SARS‐CoV‐2‐related CoVs (RatG13, PCoV‐GD, PCoV‐GX) other human (SARS‐CoV, MERS‐CoV, HCoV‐NL63, HCoV‐229E). Fourth, administrated an inhalation solution (IPB29‐IS) Syrian hamsters exhibited high therapeutic preventive efficacies Delta or variant. Fifth, pharmacokinetic profiles safety pharmacology IPB29‐IS were extensively characterized, providing data support evaluation humans. conclusion, our studies demonstrated for fusion inhibitors offered ideal drug candidate coronaviruses.

Language: Английский

Citations

4
The comprehensive insights into the B-cells-mediated immune response against COVID-19 infection amid the ongoing evolution of SARS-CoV-2 DOI
Manish Dhawan, Nanamika Thakur, Manish Sharma

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 185, P. 117936 - 117936

Published: March 8, 2025

Language: Английский

Citations

0
Comprehensive preclinical characterization of IPB29, a pan-coronavirus fusion inhibitor under clinical trials DOI
Yuanmei Zhu,

Zhongcai Gao,

Xiaoli Feng

et al.

Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106154 - 106154

Published: March 1, 2025

Language: Английский

Citations

0
Efficacy and Safety of Anti-SARS-CoV-2 Antiviral Agents and Monoclonal Antibodies in Patients with SLE: A Case-Control Study DOI Creative Commons
Giuseppe A. Ramirez, Maria Gerosa, Chiara Bellocchi

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(9), P. 1273 - 1273

Published: Aug. 22, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19) has spread pandemically with high rates of morbidity and mortality. COVID-19 also posed unprecedented challenges in terms rapid development pharmacological countermeasures to prevent or contrast SARS-CoV-2 pathogenicity. Anti-SARS-CoV-2 antiviral agents monoclonal antibodies have been specifically designed attenuate mortality vulnerable subjects, such as patients immune-mediated diseases, but evidence for the safe effective use these drugs this latter population group is scarce. Therefore, we a retrospective, multicentre, observational, case-control study analyse impact treatments systemic lupus erythematosus (SLE), paradigmatic, multi-organ autoimmune disease. We identified 21 subjects treated antivirals and/or who were matched 42 untreated by age, sex, SLE extension duration. Treated had higher baseline activity index 2000 scores [SLEDAI-2K median (interquartile range) = 4 (1–5) vs. 0 (0–2); p 0.009], prednisone doses [5 (0–10) mg (0–3) mg; 0.002], more severe symptoms five-point World Health Organisation-endorsed analogue scale [1 (0–1) (0–1); < 0.010] compared patients. There was no difference between groups outcomes sequelae, nor post-COVID-19 exacerbations. Three reported mild adverse events (two antibodies, one nirmatrelvir/ritonavir). These data suggest that anti-SARS-CoV-2 might be safely effectively used SLE, especially active at presentation.

Language: Английский

Citations

3
In Silico Evaluation of Ten Monoclonal Antibodies Neutralization Power of SARS-CoV-2 Variants EG.5, BA.2.86 and JN.1 DOI Open Access
Dana Ashoor

Published: Aug. 19, 2024

The current globally dominant SARS-CoV-2 variants are showing immune escape and reduced susceptibility to antiviral drugs. Therefore, agencies responsible for drug evaluation regulation such as the FDA EMA revising their emergency authorization use of several COVID-19 neutralizing antibodies. These MAbs proved be unlikely effective against new especially Omicron descendants pharmaceutical companies pursuing development more potent To address this issue, we used In Silico method previously developed assess 10 anti-SARS-CoV-2 antibodies propensity neutralize Omicron’s subvariants EG.5, BA.2.86 JN.1, based on comparative binding affinity 3D generated models previous experimental clinical observations. Nine these were once granted authorization, one is currently under investigation. results showed that antibody a marked increase energy EG.5 compared two significant with Pirola (BA.2.86) JN.1. This data indicates variant escapes neutralization most available therapeutic NAbs. Furthermore, potential combination could treatment countermeasure or novel variants.

Language: Английский

Citations

0
Semi-mechanistic population pharmacokinetic modeling of DZIF-10c, a neutralizing antibody against SARS-Cov-2: predicting systemic and lung exposure following inhaled and intravenous administration DOI Creative Commons

Sree Kurup,

Nieves Vélez de Mendizábal, Stephan Becker

et al.

Journal of Pharmacokinetics and Pharmacodynamics, Journal Year: 2024, Volume and Issue: 52(1)

Published: Dec. 5, 2024

DZIF-10c (BI 767551) is a recombinant human monoclonal antibody of the IgG1 kappa isotype. It acts as SARS-CoV-2 neutralizing antibody. has been developed for both systemic exposure by intravenous infusion well specific to respiratory tract application an inhaled aerosol generated nebulizer. An integrated preclinical/clinical semi-mechanistic population pharmacokinetic model was characterize profile in circulation and lungs. To inform reduce uncertainty around lungs following different methods dosing, preclinical cynomolgus monkey data combined with using allometric scaling principles. Human serum concentrations from two clinical trials were serum/plasma lung epithelial lining fluid (ELF) three studies relationship between serum/plasma, exposure. The final used predict routes administration. Simulations showed that inhalation provides immediate relevant ELF at much lower dose compared infusion. Combining therapy results high sustained circulation, thereby combining benefits By (via principles), reduced allowing evaluation alternative dosing strategies achieve desired

Language: Английский

Citations

0
In silico evaluation of ten monoclonal antibodies neutralization power of SARS-CoV-2 variants EG.5, BA.2.86 and JN.1 (Preprint) DOI
Dana Ashoor

Published: Dec. 3, 2024

BACKGROUND The current globally dominant SARS-CoV-2 variants are showing immune escape and reduced susceptibility to antiviral drugs. Therefore, agencies responsible for drug evaluation regulation such as the FDA EMA revising their emergency authorization use of several COVID-19 neutralizing antibodies. These NAbs proved be unlikely effective against new especially Omicron descendants pharmaceutical companies pursuing development more potent OBJECTIVE aim this study is evaluate antibodies neutralization power assess effectiveness available on newly emerged Eris, Pirola JN.1. METHODS Previously developed In Silico method w 10 anti-SARS-CoV-2 propensity neutralize Omicron’s subvariants EG.5, BA.2.86 JN.1, based comparative binding affinity 3D generated models previous experimental clinical observations. Nine these were once granted authorization, one currently under investigation. RESULTS Our results showed that EG.5 there was either a decrease or no change energy with 9 significant increase antibody. For (BA.2.86) observed two This data indicates variant escapes most therapeutic NAbs. However, an in may considered use. silico predictions usefulness anti consistent published data. CONCLUSIONS Computational potential existing SARS-Cov-2 very useful defining combination could treatment countermeasure Eris (EG.5), JN.1 novel variants.

Language: Английский

Citations

0