Sanofi’s Nuvaxovid COVID-19 vaccine showed significantly lower side effects than Moderna’s mNEXSPIKE in a head-to-head study, with improved tolerability and patient experience.
Written By: Dr. Anuja Badgujar, BDS
Reviewed By: Pharmacally Editorial Team
Sanofi’s Nuvaxovid (NVX-CoV2705), a protein-based COVID-19 vaccine, demonstrated significantly lower systemic reactogenicity than Moderna’s mNEXSPIKE (mRNA-1283) across all endpoints in the randomized, double-blind COMPARE study. The trial enrolled 1,000 adults in the US and was presented at the ESCMID Global Congress in Munich.
When side effects occurred with Nuvaxovid, they were generally milder and shorter in duration than those seen with mNEXSPIKE. Severe systemic symptoms such as fatigue, headache, or fever that interfere with daily activities were more than 50% less frequent, affecting fewer than 10% of recipients compared to around 20% with mNEXSPIKE.
Severe local reactions were also over 75% less common. Reflecting this improved experience, Nuvaxovid recipients were nearly twice as likely to say they would choose the same vaccine again the following year.
The study met its primary endpoint, with 83.6% of Nuvaxovid recipients experiencing at least one systemic reaction within seven days compared to 91.6% of mNEXSPIKE recipients (risk difference: 8.0%; 95% CI: 4.0%–12%; p<0.001).
Moderate-to-severe systemic symptoms were reported in 43.1% of Nuvaxovid recipients versus 61.3% with mNEXSPIKE (risk difference: 18%; 95% CI: 12%–24%; p<0.001), while moderate-to-severe local symptoms occurred in 38.7% versus 58.7%, respectively (risk difference: 20%; 95% CI: 14%–26%; p<0.001).
Dr. Marcel E. Curlin, Principal Investigator of the COMPARE study, highlighted that the lower reactogenicity observed with Nuvaxovid translated into less disruption to daily activities, which may help address vaccine hesitancy driven by concerns about side effects.
Thomas Triomphe, Executive Vice President of Vaccines at Sanofi, emphasized the importance of patient experience in supporting routine, annual immunization.
Patient-reported outcomes further supported these findings, with Nuvaxovid recipients reporting less interference with work, school, and caregiving responsibilities. More than half of participants indicated they scheduled their vaccination around anticipated side effects, underscoring the impact of tolerability on vaccination behaviour.
About COVID-19 and Nuvaxovid
COVID-19 continues to cause significant hospitalizations, particularly among older adults and individuals with underlying conditions, and is associated with increased long-term cardiovascular risks.
Nuvaxovid, originally developed by Novavax and now marketed by Sanofi, is a recombinant protein-based vaccine authorized in the US, EU, and UK. As COVID-19 becomes endemic, protein-based options such as Nuvaxovid may help improve vaccine confidence and support routine immunization uptake.
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About the Writer
Dr. Anuja Badgujar, BDS is a dentist with expertise in US healthcare data and medical data annotation. With four years of experience handling US healthcare datasets, she brings strong domain knowledge and precision to her work. She is also deeply passionate about medical writing, with a focus on translating complex medical information into clear and structured content.