Summary of COVID-19 sipavibart studies

1. Haidar et al., Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial

3,280 patient sipavibart prophylaxis RCT: 236% higher mortality (p=0.09), 1% lower hospitalization (p=1), and 32% fewer cases (p=0.0005).
RCT 3,349 immunocompromised patients showing lower symptomatic COVID-19 with sipavibart versus a combined comparator group. There was no significant difference for severe COVID-19 or hospitalization. All-cause mortality and adverse events versus placebo are reported, but for other outcomes authors only report comparison with a combined group where most patients received tixagevimab/cilgavimab. Tixagevimab/cilgavimab may have lost efficacy with variants at the time but retain side effects, potentially making the treatment look better than it would versus placebo. Table 3 shows 4x greater intervention-related serious adverse events for tixagevimab/cilgavimab compared with sipavibart. Confounding by time with the mid-trial change to placebo will also affect results. Ideally, authors will report results for concurrent treatment vs. placebo.
Jul 2025, The Lancet Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1473309924008041, https://c19p.org/haidar

2. AstraZeneca et al., A Phase II Randomized, Double-blind Study to Evaluate the Safety, Neutralizing Activity and Efficacy of AZD3152 for Pre-exposure Prophylaxis of COVID-19 in Participants Having an Increased Risk for Inadequate Response to Active Immunization (NOVELLA)

116 patient sipavibart prophylaxis RCT: 267% higher mortality (p=1) and 33% fewer symptomatic cases (p=0.64).
RCT 116 patients in Russia, showing improved nAb titers with sipavibart prophylaxis, but no significant difference for mortality or symptomatic cases.
May 2024, AstraZeneca, NCT06057064, https://clinicaltrials.gov/study/NCT06057064, https://c19p.org/azspv