Background

In the phase 1–2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern.

Methods

In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated.

Results

Covid-19–related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P=0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody–positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was −0.71 log₁₀ copies per milliliter (95% confidence interval [CI], −0.90 to −0.53) in the 1200-mg group and −0.86 log₁₀ copies per milliliter (95% CI, −1.00 to −0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups.

Conclusions

REGEN-COV reduced the risk of Covid-19–related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.)

中文翻译：

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REGEN-COV 抗体组合和 Covid-19 门诊患者的结果

背景

在适应性试验的 1-2 期部分中，REGEN-COV（单克隆抗体 casirivimab 和 imdevimab 的组合）减少了 2019 年冠状病毒病（Covid-19）患者的病毒载量和就诊次数。REGEN-COV 在体外具有针对当前引起关注的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变种的活性。

方法

在适应性试验的第 3 阶段部分，我们随机分配患有 Covid-19 和严重疾病危险因素的门诊患者接受不同剂量的静脉注射 REGEN-COV 或安慰剂。对患者进行随访至第 29 天。使用预先指定的分层分析来评估住院或死亡的终点以及症状消退的时间。还评估了安全性。

结果

REGEN-COV 2400 mg 组的 1355 名患者中有 18 名（1.3%）发生了与 Covid-19 相关的住院或任何原因死亡，安慰剂组同时接受随机分组的 1341 名患者中有 62 名（4.6%）（相对风险降低[1减去相对风险]，71.3%；P<0.001)；这些结果发生在 REGEN-COV 1200 mg 组 736 名患者中的 7 名（1.0%）和同时接受随机分组的安慰剂组 748 名患者中的 24 名（3.2%）（相对风险降低，70.4%；P=0.002 ）。每剂 REGEN-COV 的症状缓解中位时间比安慰剂组短 4 天（10 天 vs. 14 天；两项比较 P<0.001）。REGEN-COV 在各个亚组中均有效，包括基线时 SARS-CoV-2 血清抗体呈阳性的患者。两种 REGEN-COV 剂量均比安慰剂更快地降低病毒载量；从基线到第 7 天，病毒载量的最小二乘平均差异为每毫升 -0.71 log ₁₀拷贝（95% 置信区间 [CI]，-0.90 至 -0.53），在 1200 毫克组中为 -0.86 log ₁₀拷贝/毫升2400 mg 组中的毫升（95% CI，-1.00 至 -0.72）。安慰剂组（4.0%）发生严重不良事件的频率高于 1200 mg 组（1.1%）和 2400 mg 组（1.3%）；所有组中不到 0.3% 的患者发生 2 级或以上输液相关反应。

结论

REGEN-COV 降低了与 Covid-19 相关的住院或任何原因死亡的风险，并且比安慰剂更快地解决了症状并降低了 SARS-CoV-2 病毒载量。（由 Regeneron Pharmaceuticals 和其他公司资助；ClinicalTrials.gov 编号，NCT04425629。）