FDA Lifts Clinical Hold on Novavax’s COVID-19-Influenza Combination Vaccine

The US FDA has removed its clinical hold on Novavax’s Investigational New Drug (IND) application for its COVID-19-influenza combination (CIC) and stand-alone influenza vaccine candidates, according to a company press release.¹

The FDA cleared Novavax to start enrolling the planned phase 3 trial after a safety concern was found to be unrelated to the combination vaccine. Novavax said it will begin working with the clinical trial investigators and other partners to resume trial activities as soon as possible.¹

On October 16, 2024, Novavax announced the clinical trial hold after a participant who received the CIC vaccine reported symptoms of motor neuropathy in a phase 2 study that was completed in 2023.² The FDA requested additional information from Novavax, which showed a change in the event term to amyotrophic lateral sclerosis, which was found to not be related to the CIC vaccine.¹

"We thank the FDA for their partnership and thorough review of the additional information provided as part of our response package," Robert Walker, MD, chief medical officer, Novavax, said in the press release.¹ "The information provided to the FDA supported our assessment that the serious adverse event was not related to our vaccine. We plan to start our Phase 3 trial as soon as possible."

Initial phase 1/2 clinical trial results for the combined CIC vaccine demonstrated the investigational double immunization was feasible, well tolerated, and produced immunologic responses that were comparable to reference stand-alone flu and COVID-19 vaccine formulations.

More recently, Novavax announced positive topline findings at IDWeek 2024 from 2 studies of the CIC vaccine and its investigational nanoparticle influenza hemagglutinin vaccine. The company 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. At IDWeek 2024, researchers 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. Results showed that 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 CIC vaccine achieved antispike immunoglobulin G responses that were comparable to the authorized prototype NVX-CoV2373 rS vaccine and HAI responses comparable to licensed enhanced influenza comparators.

References:

U.S. FDA removes clinical hold on Novavax's COVID-19-influenza combination and stand-alone influenza phase 3 trial. News release. Novavax, Inc. November 11, 2024. Accessed November 12, 2024. https://ir.novavax.com/press-releases/2024-11-11-U-S-FDA-Removes-Clinical-Hold-on-Novavaxs-COVID-19-Influenza-Combination-and-Stand-alone-Influenza-Phase-3-Trial

Update on Novavax's COVID-19-influenza combination and stand-alone influenza phase 3 trial. News release. Novavax, Inc. October 16, 2024. Accessed November 12, 2024. https://ir.novavax.com/press-releases/2024-10-16-Update-on-Novavaxs-COVID-19-Influenza-Combination-and-Stand-alone-Influenza-Phase-3-Trial