SARS-CoV-2-neutralising antibody BGB-DXP593 in mild-to-moderate COVID-19: a multicentre, randomised, double-blind, phase 2 trialResearch in context

Summary: Background: BGB-DXP593, a neutralising monoclonal antibody against SARS-CoV-2, has demonstrated strong activity in reducing viral RNA copy number in SARS-CoV-2-infected animal models. We aimed to examine the efficacy and safety of BGB-DXP593 in ambulatory patients with mild-to-moderate COVID-19. Methods: This global, randomised, double-blind, phase 2 study (ClinicalTrials.gov NCT04551898) screened patients from 20 sites in Australia, Brazil, Mexico, South Africa, and the USA from December 2, 2020, through January 25, 2021. Patients with a first-positive SARS-CoV-2 test (positive reverse transcription–polymerase chain reaction test or authorised antigen test) ≤3 days before screening and mild-to-moderate COVID-19 symptoms for ≤7 days before treatment were randomised 1:1:1:1 to receive a single intravenous infusion of BGB-DXP593 5, 15, or 30 mg/kg, or placebo. The primary endpoint was change from baseline to Day 8 in viral RNA copies/mL as measured in nasopharyngeal swabs. Secondary endpoints were hospitalisation rate due to worsening COVID-19 and treatment-emergent adverse events (TEAEs). A prespecified exploratory endpoint was change in viral RNA copy number in saliva. Findings: Relative to the natural rate of clearance as assessed in placebo-exposed patients (−3.12 log10 copies/mL), no significant differences in nasopharygneal viral RNA copy number changes were observed (−2.93 to −3.63 log10 copies/mL) by Day 8 in BGB-DXP593-treated patients. Reductions from baseline to Day 8 in saliva viral RNA copy number were larger with BGB-DXP593 5 mg/kg (−1.37 log10 copies/mL [90% confidence interval −2.14, −0.61]; nominal p = 0.003) and 15 mg/kg (−1.26 [−2.06, −0.46]; nominal p = 0.01) vs placebo, and differences favoring BGB-DXP593 were observed by Day 3, although not statistically significant; no difference from placebo was observed for BGB-DXP593 30 mg/kg (−0.71 [−1.45, 0.04]; nominal p = 0.12). Hospitalisation rate due to COVID-19 was numerically lower with BGB-DXP593 (pooled: 2/134 patients; 1.5%) vs placebo (2/47 patients; 4.3%), although not statistically significant. Incidence of TEAEs was similar across treatment groups. No TEAE led to treatment discontinuation. Five serious TEAEs occurred, all attributed to COVID-19 pneumonia. Interpretation: BGB-DXP593 was well tolerated. Although nasopharyngeal swab SARS-CoV-2 viral RNA copy number was not significantly decreased compared with placebo, viral RNA copy number was inconsistently reduced by Day 8 in saliva at some doses as low as 5 mg/kg. Funding: BeiGene, Ltd.