FDA Lifts Clinical Hold on Novavax’s Trials for COVID-19-Influenza Combination, Standalone Influenza Vaccines

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The FDA has lifted the clinical hold on Novavax’s Investigational New Drug Application for its Phase III trials of a COVID-19-influenza Combination (CIC) vaccine and standalone influenza vaccine, following the determination that Novavax satisfactorily addressed all issues with the application. Moving forward, the Phase III trials are cleared to begin recruitment, with Novavax working with trial investigators and other involved parties to resume recruitment as soon as possible.1

"We thank the FDA for their partnership and thorough review of the additional information provided as part of our response package," said Robert Walker, MD, chief medical officer, Novavax, in a press release. "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 III trial as soon as possible."

The clinical hold was first announced last month, with the FDA citing a report of a serious adverse event involving motor neuropathy in a participant from a prior Phase II trial as the reason for the hold. Following a reclassification as amyotrophic lateral sclerosis, which was deemed to not be associated with the trial, the FDA reversed course. As a result, the federal agency deemed that the data submitted by Novavax was sufficient, with activities expected to resume in the near future.²

"We are working closely with the FDA to provide the necessary information that will allow them to better understand this observation and resolve the clinical hold," said Walker, in a previous press release. "It is important to note 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 III trial as soon as possible."

The trials for these vaccines will involve Novavax’s Matrix-M adjuvant technology, which works with protein nanoparticles to enhance the immune system response to the company’s vaccines. According to the company, it is derived from saponins, naturally occurring compounds in the bark of the Quillaja Saponaria tree, known for a long history of being used for medicinal purposes and have been used in a number of licensed vaccines. Novavax also stated that across a number of Phase I-III studies, close to 50,000 patients demonstrated promise and has been well tolerated.³

According to the Centers for Disease Control and Prevention, cases of Influenza were up 1.3% during the week ending November 2, 2024. Additionally, outpatient visits due to respiratory illnesses jumped 2.4%. Despite seasonal influenza activity remaining low overall, there has been a small increase in pediatric cases. Additionally, the first pediatric death of the influenza season was reported in the same week, and another from last year’s influenza season was reported as well, resulting in a total of 204 deaths during the 2023-2024 influenza season. Despite these numbers, the overall mortality rate has remained at 0.04%.⁴

In terms of COVID, there was a positivity rate of 4.8% for the week ending on November 2, 2024, up 5.2% from the previous two weeks. There was a 0.5% rate of emergency department visits resulting from COVID, representing a 12% decrease from the previous week. In total, there was a death rate of 1.2%, down 9.1% from the previous week.⁵

References

1. U.S. FDA Removes Clinical Hold on Novavax's COVID-19-Influenza Combination and Stand-alone Influenza Phase 3 Trial. Novavax. November 11, 2024. Accessed November 11, 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

2. Update on Novavax's COVID-19-Influenza Combination and Stand-alone Influenza Phase 3 Trial. Novavax. October 16, 2024. Accessed November 11, 2024. https://ir.novavax.com/press-releases/2024-10-16-Update-on-Novavaxs-COVID-19-Influenza-Combination-and-Stand-alone-Influenza-Phase-3-Trial

3. Our Matrix-M™ adjuvant technology. Novavax. Accessed November 11, 2024. https://www.novavax.com/what-we-do/matrix-m-adjuvant-technology

4. Weekly US Influenza Surveillance Report: Key Updates for Week 44, ending November 2, 2024. CDC. Accessed November 11, 2024. https://www.cdc.gov/fluview/surveillance/2024-week-44.html

5. United States COVID-19 Deaths, Emergency Department (ED) Visits, and Test Positivity by Geographic Area. CDC. Accessed November 11, 2024. https://covid.cdc.gov/covid-data-tracker/#maps_percent-covid-deaths