Sanofi’s Nuvaxovid exhibits 50% fewer severe side effects than Moderna’s mRNA booster

FRANCE—Sanofi has reported that its protein-based COVID-19 vaccine Nuvaxovid showed lower reactogenicity than Moderna’s next-generation mRNA vaccine mNexspike in a head-to-head clinical trial conducted in the United States.

The phase 4, double-blind study enrolled 1,000 adults and compared tolerability outcomes between the two vaccines in a real-world setting.

Nuvaxovid demonstrated statistically significant lower side effects across all pre-specified endpoints when compared with mNexspike.

Participants receiving Nuvaxovid reported milder and shorter-lasting symptoms, particularly in systemic reactions such as fatigue, headache, and fever.

Less than 10% of participants in the Nuvaxovid group experienced severe side effects that interfered with daily activities compared with 20% in the mNexspike group.

Injection site and systemic reactions

Injection site reactions, including pain, redness, and swelling, occurred more than 75% more frequently among mNexspike recipients than those who received Nuvaxovid.

In a blinded assessment, nearly twice as many Nuvaxovid recipients said they would choose the same vaccine type again the following year.

Researchers reported that 92% of mNexspike recipients experienced at least one systemic reaction within seven days compared with 84% of those who received Nuvaxovid.

Moderate-to-severe adverse events occurred in 61% of mNexspike recipients and in 43% of Nuvaxovid recipients.

The study did not evaluate vaccine efficacy and focused exclusively on tolerability and safety outcomes.

Study design and monitoring outcomes

Across systemic endpoints, the differences between the two vaccines remained consistent across subgroups, including age, sex, and prior vaccination status.

Both vaccine groups experienced the highest frequency of reactions within the first 48 hours following administration, with a gradual decline thereafter over the seven-day monitoring period.

Investigators also collected participant feedback on willingness to receive future vaccinations, which showed a higher proportion of Nuvaxovid recipients expressing positive acceptance compared with the comparator group, despite blinding of assignment.

Sanofi emphasized that the findings add to ongoing discussions around vaccine tolerability as a factor influencing long-term immunization adherence in seasonal COVID-19 programs across multiple regions.

Both vaccines remain authorized in multiple age groups in the United States following previous regulatory reviews and continued post-marketing surveillance requirements.

Industry context and commercial transition

The study followed Sanofi’s acquisition of Nuvaxovid from Novavax, a deal worth USD 500 million upfront and up to USD700 million in milestone payments.

The company also took over marketing responsibilities for the vaccine in Europe and the United States in the previous year.

Novavax originally developed the vaccine with support from a USD 1.6 billion government grant awarded in 2020.

Regulators approved Nuvaxovid for adults 65 and older and for individuals aged 12 to 64 with underlying risk factors such as asthma, diabetes, or chronic obstructive pulmonary disease.

Sanofi stated that improved patient experience may support broader uptake of routine COVID-19 vaccination programs globally.

Manufacturing and distribution responsibilities continue under Sanofi’s expanded global vaccine portfolio strategy across major markets worldwide globally programs.