Sanofi has recently released findings from the COMPARE study, the first randomized, double blind phase 4 trial designed to directly compare the tolerability of different COVID 19 vaccine technologies. The results, presented at the ESCMID Global Congress in Munich, show that Sanofi’s protein based Nuvaxovid (NVX CoV2705) had significantly lower systemic reactogenicity compared to Moderna’s latest mRNA vaccine, mNEXSPIKE (mRNA 1283).

Key findings on side effects and daily disruption

The study, which enrolled 1,000 adults in the US, met its primary endpoint by showing that 83.6% of Nuvaxovid recipients experienced systemic reactions within seven days, compared to 91.6% for mNEXSPIKE. More significantly, the severity and duration of these effects differed greatly between the two groups:

• Severe Systemic Symptoms: Reactions like fatigue or fever that prevent normal daily activities were over 50% less frequent with Nuvaxovid (fewer than 1 in 10 recipients vs. 1 in 5 for mRNA).

• Moderate to Severe Local Symptoms: Reactions at the injection site were 20% less frequent with Nuvaxovid.

• Patient Preference: Nuvaxovid recipients were nearly twice as likely as mRNA recipients to say they would “definitely choose” the same vaccine type again the following year.

Addressing vaccine hesitancy through patient experience

While COVID 19 remains a significant burden on global health systems, vaccination uptake has declined, with side effect concerns cited as a primary barrier. The COMPARE study highlighted this behavioral impact, noting that more than half of all participants scheduled their shots on specific days to account for anticipated “downtime.”

Leadership and investigator insights

Dr. Marcel E. Curlin, Principal Investigator and Professor of Medicine at Oregon Health & Science University, noted the practical implications for clinical practice:

“This study was designed to answer a question that matters deeply to clinicians and patients alike: how do different COVID-19 vaccines compare in terms of reactogenicity and patient experience? The answer is clear. 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, emphasized the role of tolerability in long term protection:

“The patient experience with vaccination is essential, because it determines not only whether people get vaccinated, but also whether they come back year after year for routine protection. These results show that Nuvaxovid can play a meaningful role in making routine COVID-19 vaccination a reality for more people, which is how we can help address the continued burden of this disease on patients and health systems.”

Real world relevance

Beyond clinical data, patient reported outcomes reinforced that Nuvaxovid recipients faced less disruption to work, school, and caretaking responsibilities. By providing a vaccine option with a lower physical toll, Sanofi aims to improve vaccine confidence and support the transition toward routine seasonal immunization.