Effectiveness of regdanvimab treatment for SARS-CoV-2 delta variant, which exhibited decreased in vitro activity: a nationwide real-world multicenter cohort study.

Background: Immune-evading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are emerging continuously. The clinical effectiveness of monoclonal antibody agents that exhibit decreased in vitro activity against SARS-CoV-2 variants needs to be elucidated. Methods: A nationwide, multicenter, retrospective cohort study was designed to evaluate the effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody agent. Regdanvimab was prescribed in South Korea before and after the emergence of the delta variant, against which the in vitro activity of regdanvimab was decreased but present. Mild to moderate coronavirus 2019 (COVID-19) patients with risk factors for disease progression who were admitted within seven days of symptom onset were screened in four designated hospitals between December 2020 and September 2021. The primary outcomes, O2 requirements and progression to severe disease within 21 days of admission, were compared between the regdanvimab and supportive care groups, with a subgroup analysis of delta variant-confirmed patients. Results: A total of 2,214 mild to moderate COVID-19 patients were included, of whom 1,095 (49.5%) received regdanvimab treatment. In the analysis of the total cohort, significantly fewer patients in the regdanvimab group than the supportive care group required O2 support (18.4% vs. 27.1%, P < 0.001) and progressed to severe disease (4.0% vs. 8.0%, P < 0.001). In the multivariable analysis, regdanvimab was significantly associated with a decreased risk for O2 support (HR 0.677, 95% CI 0.561-0.816) and progression to severe disease (HR 0.489, 95% CI 0.337-0.709). Among the 939 delta-confirmed patients, O2 support (21.5% vs. 23.5%, P = 0.526) and progression to severe disease (4.2% vs. 7.3%, P = 0.055) did not differ significantly between the regdanvimab and supportive care groups. In the multivariable analyses, regdanvimab treatment was not significantly associated with a decreased risk for O2 support (HR 0.963, 95% CI 0.697-1.329) or progression to severe disease (HR 0.665, 95% CI 0.349-1.268) in delta-confirmed group. Conclusions: 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.

Regdanvimab for patients with mild-to-moderate COVID-19: a retrospective cohort study and subgroup analysis of patients with the Delta variant.

OBJECTIVES: To evaluate the efficacy and safety of regdanvimab, a neutralizing antibody, in patients with mild-to-moderate SARS-CoV-2 including against the Delta variant. METHODS: A single-center, retrospective, observational cohort study in adults with confirmed COVID-19. The primary end point was the proportion of patients deteriorating with peripheral oxygen saturation <90% in room air, requiring supplemental oxygen therapy above high flow, or experiencing mortality due to COVID-19 up to day 28. RESULTS: A total of 722 patients were eligible; 418 received regdanvimab and 304 received standard of care (SoC), of whom 71.1% (297/418, regdanvimab) and 37.8% (115/304, SoC) were infected with the Delta variant. The proportion of patients with a primary end point event was significantly lower with regdanvimab than SoC (3.1% vs 9.9%; difference: -6.8 [95% confidence interval: -10.9, -2.8]; P = 0.0002). A similar trend was observed in the Delta variant subgroup (regdanvimab, 2.7% vs SoC, 7.0%; difference -4.3 [95% confidence interval: -10.8, 0.2]; P = 0.0827). The secondary efficacy end points supported the primary analysis findings in the overall cohort and Delta variant subgroup. No new safety signals were identified. CONCLUSION: 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.

Neutralizing antibody responses in vaccinated and unvaccinated individuals infected with Omicron BA.1 variant.

BACKGROUND: The Omicron variant, with numerous mutations in the spike protein, reduces vaccine-induced immunity, leading to breakthrough infections. However, vaccine protection after infection with the Omicron variant is unclear. AIMS AND METHODS: To compare the neutralizing antibody responses between unvaccinated and vaccinated individuals infected with the Omicron variant, we have collected serial plasma samples from five unvaccinated and four vaccinated individuals with Omicron variant infection, including the first Omicron breakthrough infection case in the Republic of Korea. We evaluated neutralization antibody titers against D614G, Delta, and Omicron using live virus neutralizing assay, and calculated the plaque reduction neutralizing test value. RESULTS: In patients with two-dose vaccinations, neutralizing antibodies against Omicron variant were detected in plasma collected 4-9 days post symptom onset. However, in the plasma from unvaccinated patients and those vaccinated with one dose, neutralizing antibodies against the Omicron variant at the same time point were undetectable. Next, the 1- or 2-dose vaccinated infected groups showed potent cross-neutralizing activity against D614G and Delta variants after 11-14 days. In contrast, the neutralizing antibody titers in the unvaccinated group were low or undetectable. CONCLUSIONS: The major limitation of this study is the small sample size due to the limited samples targeting the first reported cases of Omicron BA.1 variant infection in the Republic of Korea (n = 9). Nevertheless, we found that vaccinated individuals rapidly produced neutralizing antibodies against Omicron, and potent cross-neutralizing antibodies against D614G and Delta upon infection with Omicron.

Clinical Effectiveness of Regdanvimab Treatment for Mild-to-Moderate COVID-19: A Retrospective Cohort Study.

Background: In a Phase III study, regdanvimab (CT-P59) reduced the risk of hospitalization or death versus placebo in patients with mild-to-moderate coronavirus disease 2019 (COVID-19). Purpose: We performed a retrospective cohort study of patients with COVID-19 to examine the effect of regdanvimab versus standard of care (SoC) on oxygen saturation. Methods: We reviewed patients with mild-to-moderate COVID-19 confirmed by reverse transcription-polymerase chain reaction at a single hospital in the Republic of Korea. The primary efficacy end point was the proportion of patients deteriorating with peripheral capillary oxygen saturation <94% on room air up to day 28. Results: A total of 127 patients were treated for COVID-19 with regdanvimab, 190 with SoC. The proportion of patients deteriorating with peripheral capillary oxygen saturation <94% on room air up to day 28 was 13.4% with regdanvimab and 39.5% with SoC (P < 0.0001); median time (range) until sustained recovery of fever was 2.0 (0.2-14.8) and 4.2 (0.1-17.1) days, respectively. Supplemental oxygen was required by 23.6% of patients with regdanvimab and 52.1% with SoC (P<0.0001) for a mean of 6.3 and 8.7 days, respectively (P = 0.0113); no patients needed mechanical ventilation. Compared with SoC, hospitalization was shorter with regdanvimab (mean = 11.1 vs 13.6 days; 63.8% vs 31.6% discharged within 11 days; both P values < 0.0001). Fewer regdanvimab-treated patients required remdesivir (14.2% vs 43.2%; P < 0.0001). There were no deaths. Two patients had adverse reactions with regdanvimab. Conclusions: This real-world study indicates that regdanvimab can prevent deterioration in patients with mild-to-moderate COVID-19. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX).

Efficacy and Safety of Regdanvimab (CT-P59): A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial in Outpatients With Mild-to-Moderate Coronavirus Disease 2019.

Background: Regdanvimab (CT-P59) is a monoclonal antibody with neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on part 1 of a 2-part randomized, placebo-controlled, double-blind study for patients with mild-to-moderate coronavirus disease 2019 (COVID-19). Methods: Outpatients with mild-to-moderate COVID-19 received a single dose of regdanvimab 40 mg/kg (n = 100), regdanvimab 80 mg/kg (n = 103), or placebo (n = 104). The primary end points were time to negative conversion of SARS-CoV-2 from nasopharyngeal swab based on quantitative reverse transcription polymerase chain reaction (RT-qPCR) up to day 28 and time to clinical recovery up to day 14. Secondary end points included the proportion of patients requiring hospitalization, oxygen therapy, or mortality due to COVID-19. Results: Median (95% CI) time to negative conversion of RT-qPCR was 12.8 (9.0-12.9) days with regdanvimab 40 mg/kg, 11.9 (8.9-12.9) days with regdanvimab 80 mg/kg, and 12.9 (12.7-13.9) days with placebo. Median (95% CI) time to clinical recovery was 5.3 (4.0-6.8) days with regdanvimab 40 mg/kg, 6.2 (5.5-7.9) days with regdanvimab 80 mg/kg, and 8.8 (6.8-11.6) days with placebo. The proportion (95% CI) of patients requiring hospitalization or oxygen therapy was lower with regdanvimab 40 mg/kg (4.0% [1.6%-9.8%]) and regdanvimab 80 mg/kg (4.9% [2.1%-10.9%]) vs placebo (8.7% [4.6%-15.6%]). No serious treatment-emergent adverse events or deaths occurred. Conclusions: Regdanvimab showed a trend toward a minor decrease in time to negative conversion of RT-qPCR results compared with placebo and reduced the need for hospitalization and oxygen therapy in patients with mild-to-moderate COVID-19. Clinical trial registration : NCT04602000 and EudraCT 2020-003369-20.

Safety, Virologic Efficacy, and Pharmacokinetics of CT-P59, a Neutralizing Monoclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Protein: Two Randomized, Placebo-Controlled, Phase I Studies in Healthy Individuals and Patients With Mild SARS-CoV-2 Infection.

PURPOSE: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies. METHODS: In study 1.1, healthy adults were sequentially enrolled to receive CT-P59 10, 20, 40, or 80 mg/kg or placebo. In study 1.2, adult patients with mild SARS-CoV-2 infection were enrolled to receive CT-P59 20, 40, or 80 mg/kg or placebo. Primary objectives of both studies were safety and tolerability up to day 14 after infusion. Secondary end points included pharmacokinetic properties. Study 1.2 also measured virology and clinical efficacy. FINDINGS: Thirty-two individuals were randomized to study 1.1 (6 per CT-P59 dose cohort and 8 in the placebo cohort). By day 14 after infusion, adverse events (AEs) were reported in 2 individuals receiving CT-P59 20 mg/kg (headache and elevated C-reactive protein levels) and 1 receiving CT-P59 40 mg/kg (pyrexia) (all Common Terminology Criteria for Adverse Events grade 1). In study 1.2, 18 patients were randomized (5 per dose cohort and 3 in the placebo cohort). Sixteen AEs were reported in 10 patients receiving CT-P59. No AEs in either study led to study discontinuation. Greater reductions in viral titers were reported with CT-P59 than placebo in those with maximum titers >105 copies/mL. Mean time to recovery was 3.39 versus 5.25 days. IMPLICATIONS: CT-P59 exhibited a promising safety profile in healthy individuals and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. ClinicalTrials.gov identifier: NCT04525079 (study 1.1) and NCT04593641 (study 1.2).

Protection and Response of a Tertiary Hospital in South Korea to the COVID-19 Outbreak.

OBJECTIVE: Here, we present an overview of how a tertiary hospital responded to maintain necessary activities and protect patients and staff from the coronavirus disease (COVID-19) outbreak. METHODS: Gil Medical Center, a tertiary hospital in Incheon, has operated a special response team since January 21, 2020. All visitors were assessed for body temperature and respiratory symptoms, and screened for recent overseas travel. Suspected COVID-19 patients were taken to a screening clinic. All febrile patients with or without respiratory symptoms were taken to a respiratory safety clinic. An isolation ward, which consisted of 10 negative-pressure rooms, was used to treat confirmed cases. More than 120 beds were prepared for the outbreak, and patients with pneumonia were preemptively isolated. RESULTS: By May 5, 480 960 visitors were assessed at the control station, 3350 patients visited the triage center, and 1794 were treated in the respiratory safety clinic. Seventeen confirmed cases were admitted to the negative isolation ward, and 350 patients with pneumonia were preemptively isolated. A total of 2977 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction tests were performed. CONCLUSIONS: While tertiary hospitals play an important role in treating both COVID-19 patients and non-COVID-19 patients, hospital staff have to protect themselves from unexpected in-hospital transmission. A multifaceted response must be undertaken to protect tertiary hospitals and their staff during the COVID-19 epidemic.