Sanofi reported that its protein-based, non-mRNA COVID-19 vaccine, Nuvaxovid, demonstrated significantly lower systemic reactogenicity compared to mNEXSPIKE. The findings emerged from the COMPARE study, a randomized, double-blind trial involving 1,000 adults in the United States, presented at the ESCMID Global Congress in Munich, Germany.
Addressing Vaccine Hesitancy
Importantly, these results tackle a persistent challenge. Although the pandemic phase has subsided, COVID-19 continues to drive hospitalizations and deaths globally. However, vaccination uptake remains low, largely due to concerns about side effects. Therefore, improving vaccine tolerability could play a crucial role in increasing acceptance.
Key Clinical Findings
As per the Sanofi’s Press release, the study met its primary endpoint with statistical significance. Specifically, 91.6% of mNEXSPIKE recipients experienced at least one systemic reaction within seven days, compared to 83.6% of Nuvaxovid recipients. Moreover, moderate-to-severe systemic symptoms occurred in 61.3% of mNEXSPIKE recipients versus 43.1% with Nuvaxovid. Similarly, moderate-to-severe local reactions were reported in 58.7% of mNEXSPIKE recipients, compared to 38.7% among those receiving Nuvaxovid.
Notably, severe systemic symptoms—such as fatigue, headache, and fever—were more than 50% less frequent with Nuvaxovid. In addition, severe local reactions were rare and over 75% less frequent.
Enhancing Patient Experience
Beyond clinical endpoints, patient-reported outcomes further reinforced these findings. Recipients of Nuvaxovid reported less disruption to daily activities, including work, school, and caregiving. Consequently, they were nearly twice as likely to express willingness to receive the same vaccine again.
Implications for Future Vaccination
Experts emphasized that patient experience plays a critical role in vaccine uptake. Therefore, a better tolerability profile could improve confidence and encourage routine immunization. Overall, these findings position Nuvaxovid as a promising option to support sustained COVID-19 vaccination efforts.