FDA Places Clinical Hold on Novavax COVID-19-Influenza Combination Vaccine Due to Adverse Event

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The FDA has placed a clinical hold on the investigational new drug (IND) application for Novavax’s COVID-19-Influenza Combination (CIC) and stand-alone influenza vaccines because of a severe adverse event (AE) of motor neuropathy reported to occur in a trial participant of the ongoing phase 2 trial of the CIC vaccine, which completed in July 2023.1 This patient was at a site outside of the US and received the vaccine in January 2023—the serious AE was reported in September 2024.

Novavax’s chief medical officer, Robert Walker, MD, said in a statement that the company is “working closely with the FDA to provide the necessary information that will allow them to better understand this observation and resolve the clinical hold," adding that "safety is our top priority, and while we do not believe causality has been established for this serious adverse event, we are committed to working expeditiously to fulfill requests for more information from the FDA. Our goal is to successfully resolve this matter and to start our phase 3 trial as soon as possible."¹

The company noted that the investigators had been informed of this action. The existing data from prior trials in COVID-19 and influenza of Novavax’s vaccine showed no signs of motor neuropathy. In all groups of the phase 2 trial,² there were no AEs of special interest reported, no potentially immune-mediated medical conditions, nor were there treatment-related severe AEs. All told, unsolicited AEs were reported by 25% or fewer of all groups and were consistent with diagnoses in the older adult population. Compared with Fluad and Fluzone HD rates, the local and systemic symptoms were primarily mild and moderate.

The hold does not affect the IND for the company’s standalone COVID-19 vaccine. In the phase 2 trial, the highest dose stand-alone COVID-19 vaccine candidate showed statistically significant anti-S immunoglobulin G and neutralization responses about 30% higher than Novavax's prototype COVID-19 vaccine. This was achieved alongside maintenance of comparable safety and reactogenicity with the currently authorized dose level of Nuvaxovid.

According to the data from a May 2023 announcement, the CIC vaccine candidate achieved both immunoglobulin G (IgG) and neutralizing levels that were on par with Novavax's prototype COVID-19 vaccine (NVX-CoV2373), while multiple combination formulations also achieved responses that compared well with reference comparators to both SARS-CoV-2 and the 4 homologous influenza strains.²

This clinical hold news follows the FDA's positive August 2024 announcement regarding Novavax’s updated COVID-19 vaccine. This vaccine targets the Omicron variant JN1 strain (NVX-CoV2705) and was granted an emergency use authorization (EUA) for individuals aged 12 and older.³ The new vaccine features a monovalent component and replaced the previously authorized Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula).

Eligible individuals include those aged 12 years and older who are either unvaccinated, partially vaccinated with Novavax, or have received prior COVID-19 vaccines from other manufacturers. The updated vaccine requires 2 doses for unvaccinated individuals, 1 dose for those partially vaccinated with Novavax, and 1 dose for those fully vaccinated with prior COVID-19 vaccines.

References
1. Update on Novavax's COVID-19-Influenza Combination and Stand-alone Influenza Phase 3 Trial. Novavax. News release. October 16, 2024. Accessed October 16, 2024. https://www.prnewswire.com/news-releases/update-on-novavaxs-covid-19-influenza-combination-and-stand-alone-influenza-phase-3-trial-302277807.html

2. Positive Phase 2 Topline Results Show Novavax's COVID-Influenza Combination, Stand-alone Influenza and High-dose COVID Vaccine Candidates Demonstrate Robust Immune Responses. Novavax. News release. May 9, 2023. Accessed October 16, 2024. https://www.prnewswire.com/news-releases/positive-phase-2-topline-results-show-novavaxs-covid-influenza-combination-stand-alone-influenza-and-high-dose-covid-vaccine-candidates-demonstrate-robust-immune-responses-301819043.html