Sanofi's Nuvaxovid Shows Lower Reactogenicity Than mRNA Rival in Phase 4 Trial

Sanofi now has head-to-head Phase 4 data positioning its protein-based COVID-19 vaccine, Nuvaxovid (NVX-CoV2705), as a lower-reactogenicity alternative to Moderna's mRNA-1283 (mNEXSPIKE). The COMPARE study, a randomized, double-blind trial enrolling 1,000 US adults, met its primary endpoint with statistical significance: 83.6% of Nuvaxovid recipients experienced at least one systemic reaction within seven days versus 91.6% for mNEXSPIKE (risk difference: 8.0%; 95% CI: 4.0%–12%; p<0.001). For manufacturers, formulary decision-makers, and public health authorities grappling with persistently low COVID-19 booster uptake, these tolerability differentials could reshape how seasonal vaccination programs are structured and which products are prioritized in institutional procurement.

The data, presented April 18, 2026, at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global Congress in Munich, showed consistent separation across all pre-specified endpoints. Moderate-to-severe (Grade 2 or 3) systemic symptoms occurred in 43.1% of Nuvaxovid recipients compared to 61.3% for mNEXSPIKE (risk difference: 18%; 95% CI: 12%–24%; p<0.001). Moderate-to-severe local reactions followed a similar pattern: 38.7% versus 58.7% (risk difference: 20%; 95% CI: 14%–26%; p<0.001). Severe systemic symptoms that prevented normal daily activities were more than 50% less frequent with Nuvaxovid, affecting fewer than one in ten recipients compared to one in five for the mRNA comparator. Severe local reactions with Nuvaxovid were rare and more than 75% less frequent than with mNEXSPIKE. When side effects did occur with Nuvaxovid, they were less severe and shorter in duration.

Patient-reported outcomes reinforced the clinical findings. Nuvaxovid recipients were nearly twice as likely as mNEXSPIKE recipients to say they would definitely choose the same vaccine type again the following year. This metric carries direct implications for annual revaccination compliance, a persistent weak point in seasonal COVID-19 programs even as the virus continues to drive significant hospitalizations and deaths globally during seasonal peaks.

Dr. Marcel E. Curlin, principal investigator and Professor of Medicine at Oregon Health & Science University, stated: "Across every measure we evaluated, we observed that the recombinant protein-based vaccine consistently exhibited lower reactogenicity and less disruption to patient activities than the comparator mRNA vaccine. Individuals cite side effects as a reason they avoid COVID-19 vaccination. These differences could have a significant impact on improving vaccination uptake." Thomas Triomphe, Executive Vice President of Vaccines at Sanofi, noted that the patient experience with vaccination "determines not only whether people get vaccinated, but also whether they come back year after year for routine protection."

Source: Sanofi press release via GlobeNewswire, April 18, 2026. Data presented at ESCMID Global Congress, Munich, Germany.