Retrospective nested study of demographic characteristics, lethality and discharge rate of COVID-19 inpatients in central south of Bulgaria

Introduction: SARS-CoV-2 infection has affected more than 683 million people worldwide with 6.8 million deaths. Unfortunately, Bulgaria is one of the most severely affected European Union (EU) member-states with one of the highest mortality rates. Aim: The study aims to provide a description of the demographic characteristics, discharge rate, and fatality rate of COVID-19-diagnosed patients in one region of Central South Bulgaria in 2021. Materials and methods: A retrospective nested case series study was conducted among patients hospitalized with a confirmed diagnosis of SARS-CoV-2 infection between January 1st and December 31st, 2021. Anonymized patient data on age, sex, admission and discharge dates, treatment, and the outcome was collected from hospital electronic patient records and analyzed using descriptive statistics. Results: Data from 1630 (51% male) patients were identified. The mean age was 63.64 years (+or-15.23). 1342 (82%) of the patients were discharged. The mean age of the diseased was 70.88 years (+or-10.05). 1455 (89%) patients received only symptomatic therapy, 155 (10%) patients were treated with remdesivir (VekluryR), 11 (1%) patients were treated with casirivimab/imdevimab (RonapreveR) and 9 (1%) patients were administered regdanvimab (RegkironaR). Conclusions: The study results demonstrate that Bulgarian patients with COVID-19 were treated according to the best global and national evidencebased guidelines. Lethality and discharge rates are in concordance with global trends and outcomes.

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.

Computational approach for binding prediction of SARS-CoV-2 with neutralizing antibodies.

Coronavirus disease 2019 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as a severe pandemic and caused enormous global health and economical damage. Since December 2019, more than 197 million cases have been reported, causing 4.2 million deaths. In the settings of pandemic it is an urgent necessity for the development of an effective COVID-19 treatment. While in-vitro screening of hundreds of antibodies isolated from convalescent patients is challenging due to its high cost, use of computational methods may provide an attractive solution in selecting the top candidates. Here, we developed a computational approach (SARS-AB) for binding prediction of spike protein SARS-CoV-2 with monoclonal antibodies. We validated our approach using existing structures in the protein data bank (PDB), and demonstrated its prediction power in antibody-spike protein binding prediction. We further tested its performance using antibody sequences from the literature where crystal structure is not available, and observed a high prediction accuracy (AUC = 99.6%). Finally, we demonstrated that SARS-AB can be used to design effective antibodies against novel SARS-CoV-2 mutants that might escape the current antibody protections. We believe that SARS-AB can significantly accelerate the discovery of neutralizing antibodies against SARS-CoV-2 and its mutants.

Evolution of Anti-SARS-CoV-2 Therapeutic Antibodies.

Since the first COVID-19 reports back in December of 2019, this viral infection caused by SARS-CoV-2 has claimed millions of lives. To control the COVID-19 pandemic, the Food and Drug Administration (FDA) and/or European Agency of Medicines (EMA) have granted Emergency Use Authorization (EUA) to nine therapeutic antibodies. Nonetheless, the natural evolution of SARS-CoV-2 has generated numerous variants of concern (VOCs) that have challenged the efficacy of the EUA antibodies. Here, we review the most relevant characteristics of these therapeutic antibodies, including timeline of approval, neutralization profile against the VOCs, selection methods of their variable regions, somatic mutations, HCDR3 and LCDR3 features, isotype, Fc modifications used in the therapeutic format, and epitope recognized on the receptor-binding domain (RBD) of SARS-CoV-2. One of the conclusions of the review is that the EUA therapeutic antibodies that still retain efficacy against new VOCs bind an epitope formed by conserved residues that seem to be evolutionarily conserved as thus, critical for the RBD:hACE-2 interaction. The information reviewed here should help to design new and more efficacious antibodies to prevent and/or treat COVID-19, as well as other infectious diseases.

Efficacy and safety of regdanvimab in patients with mild to moderate COVID-19: A rapid review and meta-analysis.

AIMS: This study aimed to evaluate the efficacy and safety of regdanvimab, an anti-SARS-COV-2 monoclonal antibody approved by the European Medicines Agency in November 2021, for the treatment of confirmed COVID-19 disease. METHODS: Cochrane Library, PubMed, medRxiv and Google Scholar were searched for relevant evidence up to October 27, 2022. The quality of included studies was assessed using the Cochrane risk of bias tools. Data were analysed using RevMan software. RESULTS: Eight studies involving 4793 patients were included. A significant difference was observed between the regdanvimab and no-regdanvimab groups in terms of length of hospital stay (mean difference [MD] = -1.15, 95% confidence interval [CI]: -1.80 to -0.43), clinical recovery (odds ratio [OR] = 2.09, 95% CI: 1.38 to 3.18), disease progression (OR = 0.23, 95% CI: 0.16 to 0.33), the need for oxygen therapy (OR = 0.33, 95% CI: 0.25 to 0.43) and duration of oxygen therapy (MD = -3.00, 95% CI: -4.44 to -1.56). However, no significant difference was detected between 2 groups regarding mortality rate (OR = 0.46, 95% CI: 0.11 to 1.89), need for mechanical ventilation (OR = 0.39, 95% CI: 0.08 to 1.89) and hospital admission rate (OR = 0.61, 95% CI: 0.35 to 1.03). The incidence of adverse events was similar in both groups (OR = 0.96, 95% CI: 0.77 to 1.18). CONCLUSION: Regdanvimab was not effective in reducing mortality and hospital admission rate in patients with mild to moderate COVID-19, but it was effective in improving other efficacy outcomes. Further research is needed to confirm these findings.

[Efficacy and safety of regdanvimab in patients with mild/moderate COVID-19 and high risk of progression of the disease: a retrospective study in a short-term stay unit].

BACKGROUND: The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease. AIM: To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit. MATERIALS AND METHODS: Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. INCLUSION CRITERIA: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). EXCLUSION CRITERIA: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR. STATISTICS: Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the KaplanMeier method. The significance level was determined at p0.05. RESULTS: A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study. CONCLUSION: In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.

Use of the Monoclonal Antibody Regdanvimab to Treat Patients Hospitalized with COVID-19: Real-World Data during the Delta Variant Predominance.

Regdanvimab is the only monoclonal antibody available in Korea that targets severe acute respiratory syndrome coronavirus 2. We retrospectively evaluated the clinical characteristics of 374 adults hospitalized with coronavirus disease 2019 (COVID-19) who were treated with regdanvimab from September through December 2021. In total, 322 (86.1%) patients exhibited risk factors for disease progression. Most patients (91.4%) improved without additional treatment. No patient died or was transferred to intensive care. This study shows that regdanvimab prevented disease progression in high-risk patients with mild to moderate COVID-19 infections during Delta variant predominance.

A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019.

Background: We evaluated clinical effectiveness of regdanvimab (CT-P59), a severe acute respiratory syndrome coronavirus 2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate coronavirus disease 2019 (COVID-19), primarily Alpha variant. Methods: This was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19 were randomized to single-dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard of care. The primary endpoint was COVID-19 disease progression up to day 28 among "high-risk" patients. Key secondary endpoints were disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients). Results: Of 1315 randomized patients, 880 were high risk; the majority were infected with Alpha variant. The proportion with disease progression was lower (14/446, 3.1% [95% confidence interval {CI}, 1.9%-5.2%] vs 48/434, 11.1% [95% CI, 8.4%-14.4%]; P < .001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27-11.05 days] vs not reached [95% CI, 12.35-not calculable]; P < .001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non-high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5 of (4/652 [0.6%] regdanvimab and 1/650 [0.2%] placebo). Conclusions: Regdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the Omicron variant. Clinical Trials Registration: NCT04602000; 2020-003369-20 (EudraCT).

Monoklonale Antikörper gegen das Spike-Protein des SARS-CoV-2-Virus Casirivimab/Imdevimab, Regdanvimab, Sotrovimab und Tixagevimab/Cilgavimab

The monoclonal antibodies casirivimab/imdevimab, regdanvimab, sotrovimab and tixagevimab/cilgavimab are approved in the European Union for the treatment of SARS-CoV-2 infection. They target the spike protein of SARS-CoV-2 and are administered prophylactically after infection in patients at increased risk of severe disease progression. Their approvals are based on randomized controlled trials, in which the drugs could lower the risk for the primary endpoint hospitalization and death. The relative risk reductions were as follows: casirivimab/imdevimab 72,5 % (p < 0,0001);regdanvimab 72,1 % (p < 0,0001);sotrovimab 79,0 % (p < 0,0001).

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).

Real World Experience with Regdanvimab Treatment of Mild-to-Moderate Coronavirus Disease-19 in a COVID-19 Designated Hospital of Korea.

BACKGROUND: Real-world clinical data concerning regdanvimab, a monoclonal antibody treatment for patients with mild-to-moderate coronavirus disease 2019 (COVID-19), are urgently needed. Here, we describe our experience with regdanvimab. MATERIALS AND METHODS: This retrospective cohort study enrolled high-risk adults with mild-to-moderate COVID-19 who were admitted to a dedicated COVID-19 hospital in Korea from March to September 2021. We used multiple logistic regression and propensity score-matching to compare the outcomes of patients who did or did not receive regdanvimab. The primary outcome was in-hospital progression to severe or critical status, or death. RESULTS: Of 586 patients eligible for regdanvimab, 256 patients who received regdanvimab and 251 untreated patients were included. The median age was 66 years and 47.5% were men. The most common underlying illnesses were hypertension (53.8%) and diabetes (36.9%). Patients were admitted to the hospital at a median of 2 days after symptom onset; regdanvimab was administered at a median of 3 days after symptom onset. Multivariate analysis indicated that regdanvimab significantly reduced the risk of disease progression during hospitalization [odds ratio (OR): 0.285; 95% confidence interval (CI): 0.144 - 0.564]. In a 1:1 propensity score-matched cohort (172 patients in either group), regdanvimab also decreased the risk of progression (OR: 0.162; 95% CI: 0.068 - 0.386). CONCLUSION: In high-risk patients with mild-to-moderate COVID-19, regdanvimab decreased the risk of progression to severe COVID-19.

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.

Effectiveness and Safety of Regdanvimab in Patients With Mild-To-Moderate COVID-19: A Retrospective Cohort Study.

BACKGROUND: Regdanvimab has decreased the time to clinical recovery from coronavirus disease 2019 (COVID-19) and lowered the rate of oxygen therapy according to the results from phase 2/3 randomized controlled trial. More information is needed about the effects and safety of regdanvimab. METHODS: We analyzed data for patients with high-risk mild or moderate COVID-19 being admitted to Busan Medical Center between December 1, 2020 and April 16, 2021. A propensity score (PS) matched analysis was conducted to compare patients treated with and without regdanvimab. The primary outcome was in-hospital death or disease aggravation which means the need for oxygen therapy (low- or high-flow oxygen therapy and mechanical ventilation) and secondary outcomes comprised the length of hospital stay and adverse reactions. RESULTS: Among 1,617 selected patients, 970 (60.0%) were indicated for regdanvimab. Of these, 377 (38.9%) were administered with regdanvimab. Among a 1:1 PS-matched cohort of 377 patients each treated with and without regdanvimab, 19 (5%) and 81 (21.5%) reached the composite outcome of death, or disease aggravation, respectively (absolute risk difference, -16.4%; 95% confidence interval [CI], -21.1, -11.7; relative risk difference, 76.5%; P < 0.001). Regdanvimab significantly reduced the composite outcome of death, or disease aggravation in univariate (odds ratio [OR], 0.194; 95% CI, 0.112-0.320; P < 0.001) and multivariable-adjusted analyses (OR, 0.169; 95% CI, 0.095-0.289; P < 0.001). The hospital stay was shorter for the group with than without regdanvimab. Some hematological adverse reactions were more frequent in the group without regdanvimab, but other adverse reactions did not significantly differ between the groups. CONCLUSION: Regdanvimab was associated with a significantly lower risk of disease aggravation without increasing adverse reactions.

The Effectiveness of the Use of Regdanvimab (CT-P59) in Addition to Remdesivir in Patients with Severe COVID-19: A Single Center Retrospective Study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) still has a high mortality rate when it is severe. Regdanvimab (CT-P59), a neutralizing monoclonal antibody that has been proven effective against mild to moderate COVID-19, may be effective against severe COVID-19. This study was conducted to determine the effectiveness of the combined use of remdesivir and regdanvimab in patients with severe COVID-19. METHODS: From March to early May 2021, 124 patients with severe COVID-19 were admitted to Ulsan University Hospital (Ulsan, Korea) and received oxygen therapy and remdesivir. Among them, 25 were also administered regdanvimab before remdesivir. We retrospectively compared the clinical outcomes between the remdesivir alone group [n = 99 (79.8%)] and the regdanvimab/remdesivir group [n = 25 (20.2%)]. RESULTS: The oxygen-free days on day 28 (primary outcome) were significantly higher in the regdanvimab/remdesivir group [mean ± SD: 19.36 ± 7.87 vs. 22.72 ± 3.66, p = 0.003]. The oxygen-free days was also independently associated with use of regdanvimab in the multivariate analysis, after adjusting for initial pulse oximetric saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio (severity index). Further, in the regdanvimab/remdesivir group, the lowest SpO2/FiO2 ratio during treatment was significantly higher (mean ± SD: 237.05 ± 89.68 vs. 295.63 ± 72.74, p = 0.003), and the Kaplan-Meier estimates of oxygen supplementation days in surviving patients (on day 28) were significantly shorter [mean ± SD: 8.24 ± 7.43 vs. 5.28 ± 3.66, p = 0.024]. CONCLUSIONS: In patients with severe COVID-19, clinical outcomes can be improved by administering regdanvimab, in addition to remdesivir.

Therapeutic Effect of Regdanvimab in Patients with Mild to Moderate COVID-19: Day 28 Results from a Multicentre, Randomised, Controlled Pivotal Trial

Background. Regdanvimab is a monoclonal antibody with activity against SARSCoV-2. A Phase 2/3 study with two parts is currently ongoing and data up to Day 28 of Part 1 is available while the data from 1315 patients enrolled in Part 2 are expected in June 2021. Methods. This phase 2/3, randomized, parallel-group, placebo-controlled, double-blind study with 2 parts is aimed to assess the therapeutic efficacy of regdanvimab in outpatients with mild to moderate COVID-19, not requiring supplemental oxygen therapy. Patients aged >18 with the onset of symptoms within 7 days were eligible to be enrolled. Results. In Part 1, 307 patients (101, 103, and 103 patients in the regdanvimab 40 mg/kg, regdanvimab 80 mg/kg, and placebo groups, respectively) were confirmed to have COIVD-19 by RT-qPCR at Day 1 (or Day 2). Regdanvimab significantly reduced the proportion of patients who required hospitalization or supplemental oxygen therapy compared to placebo (8.7% in the placebo vs. 4.0% in the regdanvimab 40 mg/kg). The difference in events rate was even larger in patients who met the high-risk criteria and confirmed a 66.1% reduction in patients receiving regdanvimab 40 mg/kg (Table 1). The median time to clinical recovery was shortened by 2.9 days (7.18 days for regdanvimab 40 mg/kg and 10.03 days for placebo;high-risk). Also, greater reductions from baseline viral load were shown in regdanvimab groups (Figure 1). The safety results confirmed that the regdanvimab was safe and well-tolerated. Occurrence of adverse events (Table 2) and results of other safety assessments were generally comparable among the 3 groups. The overall rate of infusion-related reaction was low and no serious adverse events or deaths were reported. The anti-drug antibody positive rate was low in the regdanvimab groups (1.4% in regdanvimab vs. 4.5% in placebo), and no antibody-dependent enhancement was reported. Conclusion. Results from the first part of the study indicate that regdanvimab may lower the rate of hospitalisation or requirement of oxygen supplementation, with the greatest benefit noted in patients at high-risk of progressing to severe COVID-19. The second part of the study remains ongoing and blinded. Therefore, results for the primary endpoint are forthcoming and will be presented at IDWeek.

Real-World Efficacy of Regdanvimab on Clinical Outcomes in Patients with Mild to Moderate COVID-19.

BACKGROUND: This study aims to evaluate the real-world effectiveness of regdanvimab on clinical outcomes in patients with mild to moderate coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational study included 152 patients (89 received regdanvimab and 63 did not) diagnosed with mild to moderate COVID-19 between August 2021 and October 2021 and admitted to Armed Forces Goyang Hospital. We collected information on the use of regdanvimab, remdesivir, dexamethasone, and supplemental oxygen; symptom severity score (SSS); and laboratory test results. A linear mixed-effects model was used to test the effectiveness of regdanvimab usage on SSS and the results of laboratory tests. A multivariate logistic regression model was used to calculate the odds ratio (OR) for additional therapeutic options, such as remdesivir, dexamethasone, and supplemental oxygen. RESULTS: The patients who received regdanvimab were older, showed a higher rate of vaccination, and had a higher Charlson comorbidity index, initial body temperature, and percentages of pneumonia at admission. The use of regdanvimab showed no interactive effects on the SSS and laboratory findings. Older age, male sex, obesity, high initial body temperature, and the presence of pneumonia at admission were associated with increased ORs for the use of these additional treatments. The use of regdanvimab reduced the probability of requiring additional therapies such as remdesivir, dexamethasone, and oxygen supplementation by 90.3% (95% confidence interval (CI), 60.3-97.6), 85.8% (95% CI, 34.2-96.9), and 89.8% (95% CI, 48.3-98), respectively. CONCLUSIONS: Regdanvimab usage was well tolerated and was associated with a decreased probability of requiring remdesivir, dexamethasone, and oxygen therapy. However, changes in SSS were not significantly different by the drug usage.

Monoclonal antibody therapies in the management of SARS-CoV-2 infection.

INTRODUCTION: Neutralizing antibodies (NAbs) that target key domains of the spike protein in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have therapeutic value because of their specificity. Depending on the targeted epitope, single agents may be effective, but combined treatment involving multiple NAbs may be necessary to prevent the emergence of resistant variants. AREAS COVERED: This article highlights the accelerated regulatory processes established to facilitate the review and approval of potential therapies. An overview of treatment approaches for SARS-CoV-2 infection, with detailed examination of the preclinical and clinical evidence supporting the use of NAbs, is provided. Finally, insights are offered into the potential benefits and challenges associated with the use of these agents. EXPERT OPINION: NAbs offer an effective, evidence-based therapeutic intervention during the early stages of SARS-CoV-2 infection when viral replication is the primary factor driving disease progression. As the pandemic progresses, appropriate use of NAbs will be important to minimize the risk of escape variants. Ultimately, the availability of effective treatments for COVID-19 will allow the establishment of treatment algorithms for minimizing the substantial rates of hospitalization, morbidity (including long COVID) and mortality currently associated with the disease.