Novavax COVID vaccine: U.S. FDA flags risk of heart inflammation

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The U.S. Food and Drug Administration hasraised concerns about a possible risk of heart inflammation from Novavax Inc’s (NVAX.O) COVID-19 vaccine, even as the company’s data showed it could reduce the chances of mild-to-severe disease.

In a press release dated June 3, Novavax wrote:


Jun 3, 2022

Throughout the pandemic, as publicly available vaccines have been administered, there have been numerous investigations into findings related to myocarditis. We have learned that we can expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk. Myocarditis is most often caused by nonspecific viral infections.  

The data from our placebo-controlled studies show that overall, in our clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%). Furthermore, in the post-crossover portions of our studies, the cases we have seen are all within the expected rate.  

Based on our interpretation of all the clinical data supporting NVX-CoV2373, including over 50,000 participants in clinical trials, we believe there is insufficient evidence to establish a causal relationship. We will continue to monitor all adverse events, including myocarditis and pericarditis.  

link: https://ir.novavax.com/Novavax-Statement-on-US-FDA-Briefing-Document-Related-to-Myocarditis-Pericarditis


There were 6 cases of inflammation in the vaccine arm, in a 30,000 person study, the FDA reported, compared to 1 in the control group. And the company’s researchers found the numbers unalarming, saying that they fit within well-established ranges. The FDA, though, was not so sanguine.

The events of myocarditis/pericarditis are concerning for a causal association with NVX-CoV2373 for the following reasons:

  • 1) five events were reported within 2 weeks of vaccination,
  • 2) only 1 event had a clearly identified alternative etiology (COVID-19) strongly associated with myocarditis, and other events had only circumstantial evidence of potentially plausible alternative etiologies, and
  • 3) four of the events occurred in young men, a subject population known to be at higher risk for mRNA COVID-19 vaccine-associated myocarditis.

Novavax is making a late bid for entry in the US Covid market, which has been essentially under the control of Pfizer/BioNTech and Moderna — the two key mRNA rivals who quickly scored emergency approvals and reaped billions in quick rewards. J&J recently was required to dramatically narrow the use of its vaccine, the only other one approved in the US.

Aside from the mRNA rivals, though, other vaccines have been bedeviled by worries about safety issues, something that afflicted both J&J and AstraZeneca, though the numbers of people who might have been threatened were always tiny, sparking a row over the benefit/risk profile as the country fought off a virus that has now killed more than a million Americans.

In late January, Novavax announced that it had submitted a request for the FDA to authorize its coronavirus vaccine for emergency use in the United States.

In November, Indonesia became the first country to grant emergency use authorization of Novavax’s vaccine. It has since been authorized in the European Union, the United Kingdom, Canada, South Korea, Australia, India, the Philippines and New Zealand, among other countries.

Even though most adults in the United States have been vaccinated against Covid-19, the head of the company has said that it sees Novavax’s vaccine as a potential option for booster doses, regardless of which type of vaccine was given for a person’s initial doses.

Novavax’s vaccine was developed as a protein subunit vaccine, a more traditional type of technology than the mRNA used for the Moderna and Pfizer vaccines. Other examples of subunit vaccines are the hepatitis B and pertussis vaccines.

“We believe our vaccine offers a differentiated option built on a well-understood protein-based vaccine platform that can be an alternative to the portfolio of available vaccines to help fight the Covid-19 pandemic,” Novavax CEO Stanley Erck said in a statement in January.

Novavax’s protein-based coronavirus vaccine relies on something called recombinant nanoparticle technology and Novavax’s adjuvant, called Matrix-M, to stimulate an immune response and high levels of neutralizing antibodies.

Protein-based vaccines like Novavax’s work by getting the body’s immune system to recognize little modified pieces of the virus it’s targeting. In Novavax’s case, that means pieces of the coronavirus spike protein.

When the genetic sequence for the virus that causes Covid-19 was published, scientists around the world quickly identified it as a coronavirus because of the “spike proteins” on its surface. These spikes form large protrusions, giving coronaviruses the appearance of wearing crowns, and “corona” is the Latin word for “crown.”

Novavax scientists identified the gene for the spike protein and created a modified version of that gene. The researchers cloned the genes into a baculovirus that infects insects. They then infected moth cells — specifically, cells from the fall armyworm — prompting them to produce the coronavirus spike protein.

These virus-like nanoparticles were harvested to make Novavax’s vaccine.

“The whole idea of the vaccine is to show the immune system something that looks, tastes and acts like a virus, with the exception that it doesn’t make you sick. So we made the spike protein. We put it in a particle — basically, like a soap bubble — and it’s the size of the virus,” Dr. Gregory Glenn, president of research and development for Novavax, told CNN last year.

“It’s not infectious. We never touch the coronavirus itself,” Glenn added. “Then that is given to people, and they make an immune response that’s very much focused just on the spike — and I would say, the hallmark of our vaccine is, it gives a very strong immune response with very few side effects, and the dose is very small and the vaccine can be stored with normal refrigerated temperatures.”

Novavax starts Phase 3 trial of Omicron-specific booster

As Novavax seeks emergency use authorization of its NVX-CoV2373 vaccine, it also is studying a separate vaccine that specifically targets the Omicron variant, called NVX-CoV2515. The company announced this week that it has started a Phase 3 trial of this vaccine, assessing its safety and efficacy as a booster shot.

“The trial will also seek to determine the antibody responses to a bivalent vaccine, containing both NVX-CoV2373 and NVX-CoV2515, administered in participants who have received a booster series of an mRNA vaccine,” Novavax said in a news release.

The trial will analyze the Omicron-specific vaccine and a bivalent vaccine in more than 1,000 participants in Australia.

Two doses of either the Omicron-specific vaccine or the original NVX-CoV2373 vaccine will be given after three doses of either the Pfizer-BioNTech and/or Moderna vaccines that were received at least three months before participants joined the trial.

Similarly, two doses of the Omicron-specific vaccine or the original NVX-CoV2373 will be given after two doses of either mRNA vaccines received at least six months before joining the trial.

Two doses of the bivalent vaccine will be administered in participants vaccinated with three doses of either mRNA vaccine at least three months before joining the trial.

The trial will last about 10 months, and initial results are expected in the second half of this year.

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