Phase 3 results show immune response and tolerability in adults 65 and older, following phase 2 findings.
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Image credits: Novavax
Novavax Inc has announced initial results from its phase 3 clinical trial evaluating its COVID-19–influenza combination vaccine (CIC) and a stand-alone trivalent influenza vaccine candidate (tNIV) in older adults. The trial enrolled approximately 2000 participants aged 65 and older and showed that both vaccine candidates generated neutralizing antibody responses comparable to licensed vaccines—Nuvaxovid for COVID-19 and Fluzone High-Dose for influenza. More than 98% of reported adverse events were mild or moderate, with no new safety concerns identified. The reactogenicity profiles were consistent with previous trials and comparable vaccines.1
This descriptive phase 3 study assessed immunogenicity against three influenza strains, H1N1, H3N2, and B, as well as SARS-CoV-2. While not powered to evaluate efficacy, these findings will support the design of a future registrational trial.1
“Both our combination and stand-alone flu vaccine candidates induced robust immune responses and were well tolerated,” said Ruxandra Draghia-Akli, MD, PhD, Novavax’s executive vice president and head of research and development. The company continues to seek development partners and views these results as an important step toward regulatory engagement.1
These phase 3 outcomes build on previous phase 2 data demonstrating comparable safety and immunogenicity. The phase 2 trial of Novavax’s CIC and stand-alone influenza vaccines showed strong immune responses and a favorable safety profile. The CIC vaccine elicited neutralizing antibody levels on par with those seen in phase 3 trials of Novavax’s prototype COVID-19 vaccine NVX-CoV2373, and hemagglutination inhibition responses consistent with licensed influenza vaccines such as Fluzone High-Dose and Fluad.2
The stand-alone influenza vaccine candidate generated hemagglutination inhibition responses 31% to 56% higher across four influenza strains compared to Fluad and 44% to 89% higher for A strains relative to Fluzone High-Dose. Both vaccines were well tolerated, with over 98% of solicited adverse events classified as mild or moderate.2
Complementing these data, interim results from a phase 2 and 3 study of NVX-CoV2601—an updated COVID-19 vaccine targeting the Omicron XBB.1.5 variant—showed significant improvements in immune response, suggesting strong booster potential for adults in the US. Between September 2023 and January 2024, the study involved 332 adults previously vaccinated with 3 or more mRNA doses. Participants received a single dose of NVX-CoV2601, which induced neutralizing antibody titers 5.8 times higher than the original NVX-CoV2373 vaccine based on the ancestral strain. Additionally, 64% of participants receiving NVX-CoV2601 showed a seroresponse compared to 7% in the NVX-CoV2373 group.2
The COVID-19-influenza combination and stand-alone flu vaccines generated neutralizing antibody responses comparable to licensed vaccines in adults aged 65 and older.
Over 98% of adverse events were mild or moderate, with no new safety concerns or unexpected reactogenicity observed.
These initial Phase 3 findings will guide future registrational trials and regulatory discussions toward potential accelerated approval.
Safety data supported the vaccine’s booster potential, with common adverse events including injection site tenderness (52%), pain (30%), fatigue (29%), and muscle pain (29%). Serious adverse events were rare and unrelated to the vaccine.2
In a previous interview with Contagion, Novavax’s chief medical officer, Robert Walker, MD, noted that this manageable safety profile aligns with expectations for vaccines targeting evolving variants. “It’s not surprising that this combination continues to perform well, optimizing the immune response and, therefore, providing better protection over time.”2
The ongoing phase 3 trial, initiated in December 2024, aims to evaluate immunogenicity and safety of the CIC and stand-alone influenza vaccine candidates compared to Novavax’s updated 2024–2025 COVID-19 vaccine NVX-CoV2705 and licensed influenza vaccine comparators in adults aged 65 and older. The trial is designed to build upon positive phase 2 data and assess pathways toward accelerated regulatory approval. Clinical endpoints such as overall survival have not yet been assessed, with the current focus on immune responses and safety to support future regulatory submissions.
