The Food and Drug Administration (FDA) has lifted the clinical hold on Novavax's COVID-19-influenza combination (CIC) vaccine and its stand-alone influenza vaccine candidates, paving the way for the company to resume clinical trials. The initial hold was put in place on October 16, 2024, following a serious adverse event reported in a Phase 2a trial.
Adverse Event Investigation
The clinical hold stemmed from a case of motor neuropathy observed in a participant who had received the CIC vaccine during a Phase 2a trial completed in 2023. In response, Novavax worked to provide the FDA with comprehensive data to elucidate the nature of the adverse event. Robert Walker, Chief Medical Officer at Novavax, stated at the time, "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."
Causality Assessment
Following a thorough review of the additional information provided by Novavax, the FDA concluded that the patient's condition was, in fact, amyotrophic lateral sclerosis (ALS). Importantly, the FDA determined that ALS was not immune-mediated nor associated with the vaccination. "The information provided to the FDA supported our assessment that the serious adverse event was not related to our vaccine," Walker confirmed.
Matrix-M Adjuvant Technology
Novavax's vaccines utilize the Matrix-M adjuvant technology, derived from saponins found in the Chilean Soapbark tree. These Matrix-M adjuvant particles are combined with vaccine nanoparticles to enhance the immune system's response. This technology is a key component of Novavax's vaccine platform.
Next Steps
With the clinical hold lifted, Novavax is now focused on initiating Phase 3 trials for both the CIC vaccine and the stand-alone influenza vaccine. The company will collaborate closely with clinical trial investigators and other stakeholders to resume the trials as quickly as possible. Several other companies, including Pfizer/BioNTech and Moderna, are also developing COVID-19-influenza combination vaccines. While Moderna announced positive Phase 3 data in June 2024, Pfizer and BioNTech reported in August 2024 that their candidate had not met one of the primary immunogenicity objectives, showing an inferior immune response against the influenza B strain.
