IDWeek 2024: Novavax Reports Positive Data for Novel Influenza and Flu-COVID-19 Combination Vaccines

At IDWeek 2024, biotechnology company Novavax announced positive topline findings from 2 novel studies, one of an investigational nanoparticle influenza hemagglutinin vaccine and a second on a COVID-19-influenza combination (CIC) vaccine. Both are in development, the company stated, to help meet the urgent public health need for stronger protection against both respiratory viruses. ¹

The annual meeting of the Infectious Disease Society of America is being held October 16-19, in Los Angeles, CA.

The now endemic nature of SARS-CoV-2, including the ongoing evolution of variants of the virus, creates an environment in which recurrent boosters have already been considered and ostensibly introduced. Seasonal influenza vaccines are regularly less than 50% effective against the respiratory infection, according to the CDC,² and have particularly poor efficacy in older adults, as low as 10% to 13% in adults aged 65 years and older during recent seasons.^3,4 The deficiencies include limited strength and breadth of response, limited durability, and impaired fidelity of response, Novavax explained.¹

Background

Novavax had previously developed and evaluated a saponin-adjuvanted (Matrix-M) recombinant quadrivalent hemagglutinin (HA) nanoparticle influenza vaccine (qNIV) which proved noninferior to licensed comparator influenza vaccines in a phase 3 study. In previous phase 1 and 2 research with CIC formulations, the vaccine induced antibody responses comparable to the standalone qNIV and comparator COVID-19 vaccines.¹

At IDWeek, Novavax presented findings from a new qNIV study that compared the safety and immunogenicity of several formulations of qNIV versus Fluzone-HD and FLUAD as part of a larger phase 2 CIC dose confirmation trial; the CIC phase 2 study sought to confirm previous conclusions on efficacy and to explore the impact of higher recombinant Spike (rS) and Matrix-M doses against a changing immune history to SARS-CoV-2.¹

A cohort of 1571 patients in Australia and New Zealand, 864 of whom received the combination COVID-19–flu vaccine, were randomly assigned to receive 1 intramuscular dose of vaccine in 1 of 20 groups, either:

• 1 of 11 different doses or formulations of the combination vaccine
• 1 of 3 formulations of qNIV with Matrix-M
• 1 of 4 formulations of standalone rS with Matrix-M, or
• 1 of 2 influenza vaccine comparators (Fluzone HD or FLUAD)

Investigators assessed immunogenicity, including antispike IgG, SARS-CoV-2 neutralizing antibodies, and wild-type influenza HAI antibodies.

Reactogenicity was evaluated for 7 days after vaccination, while serious adverse events, adverse events of special interest, and medical attended adverse events were evaluated over the course of the study.

Findings

The qNIV vaccine produced improved wild-type hemagglutination inhibition (HAI) antibody response compared to FLUAD and Fluzone HD against strains of influenza A, including H3N2, while the combination COVID-19–flu vaccine achieved antispike immunoglobulin G responses “comparable to the authorized prototype NVX-CoV2373 rS vaccine and HAI responses comparable to licensed enhanced influenza comparators,” according to the study abstract.¹

Ultimately, investigators found that qNIV HAI and neutralizing antibody responses were significantly higher vs FLUAD and Fluzone HD “against both vaccine-homologous A strains.” The combination vaccine showed evidence of both rS and HA antigen interference, “but achieved antispike IgG and influenza HAI antibody responses” comparable to both NVX-CoV2373 and FLUAD/Fluzone HD, respectively. The investigators reported that local and systemic solicited adverse events (AEs) for all vaccine formulations were less than or comparable in rate and severity to the comparator FLUAD and Fluzone HD vaccines and that severe AEs were infrequent across study groups. No dose dependence and that was noted.¹

References
1. Shinde V, Neal S, Plested JS, et al. Immunogenicity and tolerability of the Novavax nanoparticle influenza vaccine (NIV) and COVID-influenza combination vaccine (CIC). Presented at: IDWeek 2024; October 16-19, 2024; Los Angeles, CA. Poster P-607.
2. Flu vaccine effectiveness for children and older adults. Centers for Disease Control and Prevention. August 14, 2024. https://www.cdc.gov/flu-vaccines-work/risk-groups/
3. DiazGranados CA, Robertson CA, Talbot HK, Landolfi V, Dunning AJ, Greenberg DP. Prevention of serious events in adults 65 years of age or older: A comparison between high-dose and standard-dose inactivated influenza vaccines. Vaccine 2015;33(38):4988-93. doi: 10.1016/j.vaccine.2015.07.006
4. Dunkle LM, Izikson R, Patriarca P, et al. Efficacy of recombinant influenza vaccine in adults 50 years of age or older. N Engl J Med. 2017;376:2427-2436 doi:10.1056/NEJMoa1608862