Sotrovimab
Apr. 5th, 2022 11:30 pm![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
chuka_lisВ Бразилии завершилась 3 фаза клинических испытаний сотровимаба (моноклоклональное гибридное (для улучшения работы в слизистой легких) антитело, соединяющееся с консервативным участком шипика коронавируса, который имеет минимум мутаций, обладающее некоторым нейтрализующим эффектом и мешающим формированию синцития).
Исследование было рандомизированное, двойное слепое, и в разных больницах страны. Вышло, что для пацентов группы риска развития тяжелого ковида, у тех, кто болел умеренно и легко (по 550 человек в группе), единоразовое внутривенное введение препарата снижало вероятность тяжелого ковида (оценивали по необходимости в госпитализации более чем на сутки, после препарата (или плацебо), посещения скорой, попадания в реанимацию, на вентилятор, смерть) примерно в 5 раз (1% в опыте и 6% в плацебо группе, по главному параметру, и примерно так же по 5 второстепенным).
Среди получавших препарат никто не нуждался в кислородной поддержке любого типа, хотя тяжелый ковид развился у 1% ( в группе плацебо- у 5%). Среди получавших сотровимаб никто не попал в реанимацию ( в контроле- 2%). Спустя месяц, среди тех, кто получал препарат- никто не умер, в плацебо группе умерло 2 человка. Отличия по показателям вышли достоверные.
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Sotrovimab is an Fc-engineered human monoclonal antibody that contains the LS modification to enhance half-life and respiratory mucosal delivery.7,8 In contrast to other monoclonal antibodies,9 sotrovimab targets a highly conserved epitope in the SARS-CoV-2 spike protein at a region that does not compete with binding of the angiotensin-converting enzyme 2.10,11 In addition to neutralizing SARS-CoV-2, sotrovimab has demonstrated effector functions in vitro that may contribute to immune-mediated viral clearance.7,12 Data also suggest that sotrovimab may prevent cell-cell fusion (ie, syncytia formation) unlike other antibodies that target the receptor-binding domain.13
The COVID-19 Monoclonal Antibody Efficacy Trial–Intent to Care Early (COMET-ICE) evaluated the efficacy and tolerability of sotrovimab administered intravenously in high-risk patients with mild to moderate COVID-19. The results from a preplanned interim analysis were recently published.14 The full results of this trial through the primary outcome at day 29 are presented here.Importance Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression.
Objective To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.
Design, Setting, and Participants Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021.
Interventions Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529).
Main Outcomes and Measures The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation.
Results Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, –4.53% [95% CI, –6.70% to –2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, –4.91% [95% CI, –7.50% to –2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, –3.97% [95% CI, –6.11% to –1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%).
Conclusions and Relevance Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown.
Исследование было рандомизированное, двойное слепое, и в разных больницах страны. Вышло, что для пацентов группы риска развития тяжелого ковида, у тех, кто болел умеренно и легко (по 550 человек в группе), единоразовое внутривенное введение препарата снижало вероятность тяжелого ковида (оценивали по необходимости в госпитализации более чем на сутки, после препарата (или плацебо), посещения скорой, попадания в реанимацию, на вентилятор, смерть) примерно в 5 раз (1% в опыте и 6% в плацебо группе, по главному параметру, и примерно так же по 5 второстепенным).
Среди получавших препарат никто не нуждался в кислородной поддержке любого типа, хотя тяжелый ковид развился у 1% ( в группе плацебо- у 5%). Среди получавших сотровимаб никто не попал в реанимацию ( в контроле- 2%). Спустя месяц, среди тех, кто получал препарат- никто не умер, в плацебо группе умерло 2 человка. Отличия по показателям вышли достоверные.
.
Sotrovimab is an Fc-engineered human monoclonal antibody that contains the LS modification to enhance half-life and respiratory mucosal delivery.7,8 In contrast to other monoclonal antibodies,9 sotrovimab targets a highly conserved epitope in the SARS-CoV-2 spike protein at a region that does not compete with binding of the angiotensin-converting enzyme 2.10,11 In addition to neutralizing SARS-CoV-2, sotrovimab has demonstrated effector functions in vitro that may contribute to immune-mediated viral clearance.7,12 Data also suggest that sotrovimab may prevent cell-cell fusion (ie, syncytia formation) unlike other antibodies that target the receptor-binding domain.13
The COVID-19 Monoclonal Antibody Efficacy Trial–Intent to Care Early (COMET-ICE) evaluated the efficacy and tolerability of sotrovimab administered intravenously in high-risk patients with mild to moderate COVID-19. The results from a preplanned interim analysis were recently published.14 The full results of this trial through the primary outcome at day 29 are presented here.Importance Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression.
Objective To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.
Design, Setting, and Participants Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021.
Interventions Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529).
Main Outcomes and Measures The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation.
Results Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, –4.53% [95% CI, –6.70% to –2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, –4.91% [95% CI, –7.50% to –2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, –3.97% [95% CI, –6.11% to –1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%).
Conclusions and Relevance Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown.
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Date: 2022-04-06 11:26 am (UTC)no subject
Date: 2022-04-06 09:35 pm (UTC)хорошо, что у меня есть читатели.