FDA Places Clinical Hold on Novavax COVID-19/Influenza and Standalone Influenza Vaccine Trials

The FDA has placed a clinical hold on Novavax’s investigational new drug (IND) application for its COVID-19/influzena combination and stand-alone influenza vaccine candidates. The action comes after a participant who received the combination vaccine reported experiencing motor neuropathy, a rare, acquired immune-mediated disorder that causes muscle weakness of the arms and legs.^1-3 As a result of the FDA’s clinical hold, Novavax shares fell by approximately 16%.³

The participant received the vaccine in January 2023, the trial reached its completion in July 2023, and the serious adverse event (SAE) was reported by the participant in September 2024.² Additionally, the COVID-19 IND for Novavax’s COVID-19 vaccine—which is currently the only product the company has available on the US market—is not impacted by the FDA’s clinical hold.²

Image credit: Daniel Jędzura | stock.adobe.com

According to a news release, the SAE occurred in a phase 2 trial participant who was outside of the US. The trial had reached competition in June 2023, and a phase 3 study was in development between Novavax and the FDA at the time the SAE was reported. Additionally, Novavax emphasized that AE was not linked to other vaccine candidates under study, and that there were no other cases of motor neuropathy at the time of the phase 2 trial’s duration or during prior trials. Further, cases of this AE were previously reported by some individuals who received other COVID-19 vaccines; however, this complication has not been directly linked to the vaccination.³

Novavax reports that their current adjuvanted COVID-19 vaccine (2024-2025 formula) is based off the effectiveness of the original monovalent Novavax COVID-19 vaccine and the immunogenicity of the monovalent vaccines for Omicron BA.1 and Omicron BA.5.³ Their COVID-19 vaccines are built on protein-based platform used in some vaccines for influenza, respiratory syncytial virus, and hepatitis B, and it serves as an alternative to the mRNA vaccines.^2,4

“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 Robert Walker, MD, chief medical officer of Novavax, in a news release. “It is important to note that safety is our top priority, and while we do not believe causality has been established for this SAE, 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.”²

Further, it is still important for individuals to be up to date with their vaccinations, even if they previously received doses. In a Pharmacy Times interview, Walker emphasized that although prior vaccines may offer some small level of protect, receiving the most updated formulation with the current circulating strains is best to be optimally protected from infection.⁵

Declines in vaccination rates, according to Walker, are likely because of general vaccine hesitancy and either inadequate or incorrect information that can circulate. He also acknowledged that some people may be tired of receiving annual vaccines and want to move on from the COVID-19 pandemic.⁵

“…our job, of course, is to help people understand the importance of getting vaccinated and try to call attention to this as best as we can because it's in an individual's best interest to be protected. It's important for the other family members, so they don't spread the virus to their loved ones, and it's important for our communities because we want to make sure that people who are susceptible to really bad forms of the illness, might wind up in the hospital or in the intensive care unit on a ventilator,” explained Walker during the interview. “We want to we want to make sure that those vulnerable people in our communities are protected, and the best way we do that is by protecting ourselves and reducing the opportunity for the virus to spread.”⁵

REFERENCES

1. Reuters. US FDA pauses Novavax's trial of combo COVID-flu shot on safety concerns. News release. October 16, 2024. Accessed October 17, 2024. https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-places-trials-two-novavax-vaccines-hold-2024-10-16/

2. PR Newswire. Update on Novavax's COVID-19-Influenza Combination and Stand-alone Influenza Phase 3 Trial. News release. October 16, 2024. Accessed October 17, 2024. https://www.prnewswire.com/news-releases/update-on-novavaxs-covid-19-influenza-combination-and-stand-alone-influenza-phase-3-trial-302277807.html

3. BioSpace. Novavax Shares Slide as FDA Pauses COVID/Flu Vaccine Candidates. News release. October 16, 2024. Accessed October 17, 2024. https://www.biospace.com/drug-development/novavax-shares-slide-as-fda-pauses-covid-flu-vaccine-candidates

4. Non-mrna COVID-19 vaccine information for HCP: Novavax COVID-19 vaccine, adjuvanted (2024-2025 formula). Non-mRNA COVID-19 Vaccine Information for HCP | Novavax COVID-19 Vaccine, Adjuvanted (2024-2025 Formula). Accessed October 17, 2024. https://us-hcp.novavaxcovidvaccine.com/

5. COVID-19 Vaccines Targeting New Variants for 2024-2025 Season. Pharmacy Times. September 2, 2024. Accessed October 17, 2024. https://www.pharmacytimes.com/view/covid-19-vaccines-targeting-new-variants-for-2024-2025-season