Sanofi (Nasdaq: SNY) reported that its recombinant protein-based COVID-19 vaccine Nuvaxovid produced statistically significant lower systemic reactogenicity than Moderna's mNEXSPIKE in a Phase IV head-to-head trial, with the gap driven by a meaningful reduction in both the frequency and severity of post-vaccination reactions across all pre-specified endpoints.
The COMPARE study is a randomized, double-blind Phase IV trial that enrolled 1,000 adults in the US and is the first study powered specifically to compare the tolerability profiles of these two vaccines head-to-head. For Nuvaxovid recipients, 83.6% experienced at least one systemic reaction within seven days versus 91.6% with mNEXSPIKE (p<0.001). Moderate-to-severe systemic reactions were also less frequent (43.1% vs 61.3%), with severe reactions reduced by more than 50%.
The double-blind study, conducted in the US, is the first powered specifically to compare tolerability between the two vaccines. No detailed safety signals beyond reactogenicity were disclosed. The data come as COVID-19 booster uptake declines, with side-effect concerns a key barrier. A tolerability advantage in a controlled head-to-head setting may carry more weight than prior observational comparisons, though most participants in both arms still reported at least one reaction.
Nuvaxovid is currently the only approved non-mRNA COVID-19 vaccine in the US, potentially giving it a differentiated position against established mRNA products. The data were presented at the ESCMID Global Congress 2026.
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