Tixagevimab + Cilgavimab: First Approval

Drugs, Год журнала: 2022, Номер 82(9), С. 1001 - 1010

Опубликована: Июнь 1, 2022

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A Critical Analysis of the Use of Cilgavimab plus Tixagevimab Monoclonal Antibody Cocktail (Evusheld™) for COVID-19 Prophylaxis and Treatment

Viruses, Год журнала: 2022, Номер 14(9), С. 1999 - 1999

Опубликована: Сен. 9, 2022

Evusheld® (tixagevimab + cilgavimab; AZD7442) was the first anti-Spike monoclonal antibody (mAb) cocktail designed not only for treatment but also with pre-exposure prophylaxis in mind. The immunoglobulins were engineered prolonged half-life by modifying Fc fragment, thus creating a long-acting (LAAB). We review here preclinical development, baseline and treatment-emergent resistance, clinical efficacy from registration trials, real-world post-marketing evidence. combination initially approved at time of SARS-CoV-2 Delta VOC wave based on trial conducted unvaccinated subjects when Alpha dominant. Another proved as early patients led to authorization BA.4/5 wave. Tixagevimab ineffective against any Omicron sublineage, so cilgavimab has far been ingredient which made difference. Antibody monotherapy high risk selecting immune escape variants immunocompromised viral loads, nowadays represent main therapeutic indication therapies. Among sublineages, BA.1, recovered BA.2 BA.2.12.1, lost again BA.4/BA.5 BA.2.75. Our analysis indicated that used during phase without robust data this variant suggested several regulatory decisions regarding its use lacked consistency. There is an urgent need new randomized controlled trials vaccinated, subjects, using COVID-19 convalescent plasma control arm.

Язык: Английский

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The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19

Annals of Internal Medicine, Год журнала: 2022, Номер 175(10), С. 1401 - 1410

Опубликована: Авг. 29, 2022

Background: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding the pathogenesis COVID-19. Objective: To evaluate whether levels can predict short-term clinical outcomes identify viral factors associated hospitalized SARS-CoV-2. Design: Cross-sectional study baseline level from 2540 participants enrolled TICO (Therapeutics for Inpatients With COVID-19) platform trial August 2020 to November 2021, additional data on day 5 outcome time discharge. Setting: 114 centers 10 countries. Participants: Adults acute infection 12 days or less symptoms. Measurements: Baseline N was measured at a central laboratory. Delta variant status determined nasal swabs using reverse transcriptase polymerase chain reaction. Associations between patient characteristics were assessed both unadjusted multivariable modeling. Association elevated 1000 ng/L greater outcomes, including worsening ordinal pulmonary scale hospital discharge, evaluated logistic regression Fine–Gray models, respectively. Results: Plasma below quantification 5% enrollment, 57%. severity illness strongly level, mean 3.10-fold higher among those requiring noninvasive ventilation high-flow cannula compared room air (95% CI, 2.22 4.34). who lacked antispike antibodies (6.42 fold; 5.37 7.66) (1.73 1.41 2.13). Additional included male sex, shorter since admission, decreased remdesivir, renal impairment. In contrast, race, ethnicity, body mass index, immunocompromising conditions not levels. markedly odds worsened (odds ratio, 5.06 [CI, 3.41 7.50]) longer discharge (median, 7 vs. 4 days; subhazard 0.51 0.45 0.57]), ratios similar across all severity. Limitations: samples drawn presentation. No point-of-care test measure is currently available. Conclusion: Elevated highly clinically outcomes. Multiple are These support potential role ongoing replication patients. Primary Funding Source: U.S. government Operation Warp Speed National Institute Allergy Infectious Diseases.

Язык: Английский

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Molnupiravir, Nirmatrelvir/Ritonavir, or Sotrovimab for High-Risk COVID-19 Patients Infected by the Omicron Variant: Hospitalization, Mortality, and Time until Negative Swab Test in Real Life

Pharmaceuticals, Год журнала: 2023, Номер 16(5), С. 721 - 721

Опубликована: Май 9, 2023

Background. Several drugs which are easy to administer in outpatient settings have been authorized and endorsed for high-risk COVID-19 patients with mild-moderate disease prevent hospital admission death, complementing vaccines. However, the evidence on efficacy of antivirals during Omicron wave is scanty or conflicting. Methods. This retrospective controlled study investigated Molnupiravir Nirmatrelvir/Ritonavir (Paxlovid®) Sotrovimab against standard care (controls) three different endpoints among 386 outpatients: at 30 days; death time between diagnosis first negative swab test result. Multivariable logistic regression was employed investigate determinants hospitalization due COVID-19-associated pneumonia, whereas result by means multinomial analysis as well Cox analysis. Results. Only 11 (overall rate 2.8%) developed severe pneumonia requiring hospital: 8 controls (7.2%); 2 (2.0%); 1 (1.8%). No patient institutionalized. Compared controls, less likely (aOR = 0.16; 95% CI: 0.03; 0.89) (omitted estimate); drug 84% 100% Molnupiravir. two died (rate 0.5%), both were one (a woman aged 96 years) unvaccinated other 72 had adequate vaccination status. At analysis, negativization significantly higher treated antivirals-Nirmatrelvir/Ritonavir (aHR 1.68; 1.25; 2.26) 1.45; 1.08; 1.94). 2.03; 1.51; 2.73) four 2.48; 1.32; 4.68) doses a slightly stronger effect size viral clearance. In contrast, reduced who immune-depressed 0.70; 0.52; 0.93) those Charlson index ≥5 0.63; 0.41; 0.95) started respective treatment course 3+ days after 0.56; 0.38; 0.82). Likewise, internal (excluding care), 1.74; 1.21; 2.50) 1.96; 2.93) more turn earlier than (reference category). Nonetheless, 1.91; 1.33; 2.74) 2.20; 1.06; 4.59) vaccine again associated faster rate. Again, lower if 0.54; 0.32; 0.92). Conclusions. Molnupiravir, Nirmatrelvir/Ritonavir, all effective preventing and/or mortality attributable COVID-19. hospitalizations also decreased number Although they mortality, prescription should be carefully scrutinized double opinion, not only contain health costs but reduce risk generating resistant SARS-CoV-2 strains. 64.7% fact immunized vaccines present study. High-risk prioritize vaccination, cost-effective approach pneumonia. although antivirals, especially shedding (VST) patients, an independent VST considered secondary benefit. Indeed, recommending order control rather questionable since cheap, large spectrum harmless nasal disinfectants such hypertonic saline solutions available market proven containing VST.

Язык: Английский

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Therapeutic Antibodies in Medicine

Molecules, Год журнала: 2023, Номер 28(18), С. 6438 - 6438

Опубликована: Сен. 5, 2023

Antibody engineering has developed into a wide-reaching field, impacting multitude of industries, most notably healthcare and diagnostics. The seminal work on developing the first monoclonal antibody four decades ago witnessed exponential growth in last 10–15 years, where regulators have approved antibodies as therapeutics for several diagnostic applications, including remarkable attention it garnered during pandemic. In recent become fastest-growing class biological drugs treatment wide range diseases, from cancer to autoimmune conditions. This review discusses field therapeutic stands today. It summarizes outlines clinical relevance application treating landscape diseases different disciplines medicine. nomenclature, various approaches therapies, evolution therapeutics. also risk profile adverse immune reactions associated with sheds light future applications perspectives drug discovery.

Язык: Английский

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Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

EClinicalMedicine, Год журнала: 2023, Номер 58, С. 101939 - 101939

Опубликована: Апрель 1, 2023

Язык: Английский

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An update on the anti-spike monoclonal antibody pipeline for SARS-CoV-2

Clinical Microbiology and Infection, Год журнала: 2024, Номер 30(8), С. 999 - 1006

Опубликована: Апрель 24, 2024

Язык: Английский

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COVID-19 therapeutics

Clinical Microbiology Reviews, Год журнала: 2024, Номер 37(2)

Опубликована: Май 21, 2024

SUMMARYSince the emergence of COVID-19 in 2020, an unprecedented range therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy those often remains controversial or compromised by viral evolution. Uncertainties still persist regarding best therapies for high-risk patients, drug pipeline is suffering fatigue shortage funding. In this article, we review antiviral activity, mechanism action, pharmacokinetics, safety therapies. Additionally, summarize evidence from randomized controlled trials on various antivirals discuss unmet needs which should be addressed.

Язык: Английский

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The efficacy of tixagevimab/cilgavimab (Evusheld) in prophylaxis and treatment of COVID-19 in immunocompromised patients: a systematic review and meta-analysis

European journal of medical research, Год журнала: 2024, Номер 29(1)

Опубликована: Янв. 5, 2024

Abstract Background During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate vaccination or had low responses. Evusheld is a combined neutralizing monoclonal antibody containing tixagevimab and cilgavimab. The World Health Organization (WHO) has approved this combination as pre-exposure prophylaxis (PrEP) treatment for patients. With new variant, recommended an increase in dose from 300 to 600 mg with booster after 6 months. target of review was compare efficacy two doses, tixagevimab/cilgavimab (Evusheld) higher-risk individuals reveal if there significant difference between those doses drug. Methods In study, electronic databases (PubMed, Web Science core collection, Scopus, Cochran) were investigated articles up 31/12/2022 English using well-established search strategy. We included studies conducted patients (aged ≥ 12 years) received COVID-19. After excluding inconsistent selection criteria, 24 involved, 22 which meta-analysis. analyzed data by RevMan 5.4 program software. Results double-arm subgroup analysis, mg, administered prophylaxis, showed no infection rate, mortality needed hospitalization rate compared ( p = 0.13, 0.29, 0.25, respectively). single-arm decrease 0.0001, 0.007, As treatment, over placebo group 0.01) Conclusion This result indicated that effective prophylactic therapeutic drug infection, especially but considerable variation high doses. Further prospective randomized controlled trials (RCTs) increased population sizes are necessary show valuable benefit prevention within adverse events.

Язык: Английский

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SARS-CoV-2 resistance to monoclonal antibodies and small-molecule drugs

Cell chemical biology, Год журнала: 2024, Номер 31(4), С. 632 - 657

Опубликована: Апрель 1, 2024

Over four years have passed since the beginning of COVID-19 pandemic. The scientific response has been rapid and effective, with many therapeutic monoclonal antibodies small molecules developed for clinical use. However, given ability viruses to become resistant antivirals, it is perhaps no surprise that field identified resistance nearly all these compounds. Here, we provide a comprehensive review profile each therapeutics. We hope this resource provides an atlas mutations be aware agent, particularly as springboard considerations next generation antivirals. Finally, discuss outlook thoughts moving forward in how continue manage this, next,

Язык: Английский

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