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.

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).

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).

Regdanvimab in patients with mild-to-moderate SARS-CoV-2 infection: A propensity score-matched retrospective cohort study.

BACKGROUND: Regdanvimab (CT-P59) is a neutralizing antibody authorized in Republic of Korea for the treatment of adult patients with moderate or mild-COVID-19 who are not on supplemental oxygen and have high risk of progressing to severe disease (age ≥ 50 years or comorbidities). This study evaluated the clinical efficacy, safety and medical utilization/costs associated with real-world regdanvimab therapy. METHODS: This non-interventional, retrospective cohort study included adult patients with confirmed mild-to-moderate SARS-CoV-2 infection. Patients treated with regdanvimab were compared with controls who had received other therapies. The primary endpoint was the proportion of patients progressing to severe/critical COVID-19 or death due to SARS-CoV-2 infection up to Day 28. Propensity score matching was applied to efficacy analyses. RESULTS: Overall, 552 patients were included in the Safety and Efficacy Sets (regdanvimab, n = 156; control, n = 396) and 274 patients in the propensity score-matched (PSM) Efficacy Set (regdanvimab, n = 113; control, n = 161). In the PSM Set, the risk of severe/critical COVID-19 or death was significantly lower in the regdanvimab group (7.1% vs 16.1%, P = 0.0263); supplemental oxygen was required by 8.0% and 18.6% of patients in the regdanvimab and control groups, respectively (P = 0.0128). There were no unexpected safety findings in the regdanvimab group. Medical utilization analysis showed an overall cost reduction with regdanvimab compared with control treatments. CONCLUSIONS: Regdanvimab significantly reduced the proportion of patients progressing to severe/critical disease or dying of SARS-CoV-2 infection. This study shows the potential benefits of regdanvimab in reducing disease severity and improving medical utility in patients with COVID-19.

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).

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant.

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline.

Monoclonal antibody (mAb) therapy has been previously exploited for viral infections, such as respiratory syncytial virus pneumonia and Ebolavirus disease. In the ongoing COVID-19 pandemic, early signals of efficacy from convalescent plasma therapy have encouraged research and development of anti-SARS-CoV-2 mAbs. While many candidates are in preclinical development, we focus here on anti-SARS-CoV-2 neutralizing mAbs (or mAb cocktails) that represent the late-stage clinical pipeline, i.e., those currently in Phase 2 or Phase 3 clinical trials. We describe the structure, mechanism of action, and ongoing trials for VIR-7831, LY-CoV555, LY-CoV016, BGB-DXP593, REGN-COV2, and CT-P59. We speculate also on the next generation of these mAbs.