FDA Expresses Concern Over Myocarditis Ahead of Novavax Adcom

Pictured: Novavax/Getty Images, STR/NurPhoto

Pictured: Novavax/Getty Images, STR/NurPhoto

The FDA has expressed worries over four cases of heart inflammation, or myocarditis, that were observed in pivotal clinical trials of Novavax’s COVID-19 vaccine.

Novavax can’t seem to catch a break, at least in the United States. Company shares dropped 17% after the U.S. Food and Drug Administration released briefing papers about the company’s COVID-19 vaccine. The agency expressed worries over four cases of heart inflammation, or myocarditis, that were observed in pivotal clinical trials.

This is the same issue that has been noticed in some of the other vaccines, particularly the AstraZeneca-Oxford vaccine, although it has also been observed with the Pfizer-BioNTech and Moderna shots.

In the FDA documents, the agency said the results “raise the concern for a causal association” between the vaccine and myocarditis. One case was observed 20 days after vaccination in the placebo arm, which was unrelated. Two were associated with the treatment arm. “Data from passive surveillance during post-authorization use in other countries also indicate a higher-than-expected rate of myocarditis and pericarditis (mainly pericarditis) associated with the vaccine,” the documents state.

The documents were released ahead of a June 7 meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee. The agency indicated five of the six myocarditis/pericarditis cases were observed within two weeks of administration and four were in young men. There were almost 30,000 participants in the study, run between December 2020 and September 2021. Otherwise, overall efficacy was 90.4%, although lower, 78.6%, in people 65 years and older.

Data from the studies were prior to the Delta and Omicron variant surges, although the documents say, “based on the efficacy estimate in the clinical trial of this vaccine, it is more likely than not that the vaccine will provide some meaningful level of protection against COVID-19 due to Omicron, in particular against more severe disease.”

Novavax has stated that the number of myocarditis events in the study was “within the range of expected background cases…. Despite the wide availability of authorized or approved vaccines, the SARS-COV-2 pandemic is not well controlled in the U.S…. there remains a desire for vaccines that have been developed using well-understood technology platforms.”

Meanwhile, the company initiated a Phase III trial of its vaccine against the Omicron strain on May 31. This particular vaccine trial is of a bivalent vaccine that contains both NVX-CoV2373 and NVX-CoV2515. NVX-CoV2373 is the vaccine currently on the market in other countries and up for review in the U.S. The trial will last 10 months with initial results expected in the second half of 2022.

The Novavax vaccine uses an older, traditional type of vaccine manufacturing process where copies of the spike protein are grown in insect cells, purified and placed into nanoparticles with an immune-stimulating adjuvant. That is compared to the newer mRNA vaccines that package a segment of mRNA coding for the spike protein in a nanoparticle. Protein vaccines have been used in numerous other vaccines, such as for hepatitis B and shingles.

Novavax has struggled with manufacturing difficulties, which have delayed production around the world. Company CEO Stanley Erck indicates those problems have been resolved and “are well behind us.” The company has distributed more than 40 million doses as of March in Asia, Europe and elsewhere. The Serum Institute of India manufactured the shots for Novavax, which is based in the U.S.

On Thursday, Novavax filed for conditional marketing authorization of the vaccine (NVX-CoV2373, Nuvaxovid) in the UK as a booster dose for people 18 years and older. The submission was based on data from a Phase II trial conducted in Australia and a separate Phase II trial in South Africa. In February, it was authorized for people aged 18 and over in the UK.