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FDA advisers greenlight Novavax COVID-19 vaccine

A key committee of advisers to the U.S. Food and Drug Administration (FDA) today recommended nearly unanimously that the agency grant an emergency authorization to a COVID-19 vaccine from Novavax, opening the way for the first protein-based COVID-19 vaccine to become available to people in the United States.

The 21-0 vote, with one abstention, marks a hard-won and long-sought milestone for the small Gaithersburg, Maryland–based biotechnology company that was moribund as the pandemic began. It found a new life as it collected $2 billion to develop a vaccine, first from an international organization that supports vaccinemaking and then from the U.S. government.

“This is a case study of perseverance,” Bruce Gellin, chief of global public health strategy at the Rockefeller Foundation, said after the vote. Yet Gellin was the lone abstaining vote, saying the committee wasn’t given data on how the vaccine performs against the Omicron variants now circulating, or for how many months its protection lasts.

Still, Gellin said, “This vaccine has incredible potential.” It is easy to store and transport, lasting at refrigerator temperatures for months, unlike the dominant messenger RNA (mRNA) vaccines.

The thumbs up from the FDA advisers likely means the agency will allow the company to enter the U.S. market, as FDA usually follows its advisers’ lead. Novavax hopes holdouts skeptical of mRNA vaccines and, ultimately, others seeking booster shots will opt for its tried-and-true technology.

If it wins final authorization, the vaccine will be the fourth COVID-19 jab marketed in the United States. Unlike the other three, which deliver genetic material that directs host cells to make the coronavirus’ spike protein, Novavax’s product delivers spike protein directly to recipients. Approved vaccines for shingles, hepatitis B, and influenza use similar protein-based technology.

Just days before today’s meeting, the company’s stock price tumbled when FDA published data indicating the vaccine may rarely cause myocarditis and pericarditis, a problem that has also dogged mRNA vaccines from Moderna and the Pfizer-BioNTech collaboration. Perhaps in response to the volatility, NASDAQ froze trading of the stock today before the meeting opened.

But 21 of the 22 advisers concluded any risk posed by heart inflammation was outweighed by the benefits of a vaccine that showed 90.4% efficacy against early strains of SARS-CoV-2 in a trial involving 30,000 people in the United States and Mexico. The Novavax shot also has low “reactogenicity”—meaning immediate side effects, from painful arms to malaise. The committee recommended authorization for the two-shot series in adults 18 years and older.

“Certainly the benefits outweigh the risks,” said adviser Michael Nelson, an allergist and immunologist at the University of Virginia School of Medicine. But in response to a query from Doran Fink, acting deputy director of FDA’s vaccine approval branch, Nelson said the agency should include a warning about heart risks in the package insert. “It would be a travesty if we didn’t mention this in the … documentation for the public to show the concern that we have.”

Novavax’s vaccine, which is produced in insect cells and combined with an immune-boosting substance called an adjuvant, has already been authorized in more than 40 countries including the United Kingdom, Canada, Germany, and Australia; it has also won emergency authorizations from the European Union and the World Health Organization.

But manufacturing issues have hampered Novavax’s effort and sidelined its would-be U.S. vaccinemaking facilities. In addition, the company struggled mightily to show it could make the vaccine consistently. If authorized in the United States, the product will initially be manufactured, as all Novavax vaccine currently is, by the Serum Institute of India, one of the world’s largest vaccine manufacturers.

Myocarditis concerns may also dog the vaccine. The data revealed on 3 June by FDA described five cases of myocarditis that occurred in people in the vaccine arms of the Novavax clinical trials in the United States and the United Kingdom. Four occurred within 20 days of vaccination, a time frame during which there were no cases in the placebo arm. Three cases were in men ages 16 to 20. Young men have had the highest rates of myocarditis or pericarditis after receiving mRNA vaccines. “These events raise the concern for a causal association with this vaccine, similar to the association documented with mRNA COVID-19 vaccines,” FDA wrote.

Novavax countered that collectively across all of its clinical trials, the risk of myocarditis and pericarditis was not significantly different in the vaccine group (0.007%) and in the placebo groups (0.005%). “We believe that the totality of the clinical evidence here is not enough to establish an overall causal relationship with the vaccine,” Denny Kim, Novavax’s chief safety officer, told the FDA advisers.

But Paul Offit, a committee member and infectious disease physician at the Children’s Hospital of Philadelphia, told today’s meeting that the “handful of cases of myocarditis [that] occurred within 3 or 4 days of receiving the second dose of vaccine in young men is consistent with what was seen with the mRNA-induced myocarditis. So I think that is likely a cause and not a coincidental association.” 

The law governing emergency use authorizations (EUAs) by FDA requires that there is no “adequate, approved and available alternative” to a product. One advisory committee member asked Peter Marks, FDA’s top vaccine official, why the Novavax vaccine meets that requirement given that three other vaccines are already available to people in the United States.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Marks replied, noting that the law “allows us some leeway” to address unmet needs. “Anything we can do to get people … to be able to accept these potentially lifesaving medical products is something that we feel we are compelled to do.”

Some committee members raised eyebrows at the suggestion that the Novavax vaccine would win over a substantial number of the 27 million unvaccinated Americans with its familiar technology.

“I’m very skeptical that vaccine-hesitant people will elect to get this vaccine,” said committee member Jay Portnoy, an allergist and immunologist at Children’s Mercy Hospital. “Their hesitancy is more ideological than technological.”

But a parade of public speakers at the meeting mostly urged the committee to authorize the vaccine. “We need to … provide options to reduce excuses,” Martha Dawson, president of the National Black Nurses Association, told the advisers. “It could be the next thing that saves your life or your loved one’s life.”

When FDA’s advisers gave a green light to the Moderna and Pfizer vaccines in late 2020, the agency acted quickly to issue EUAs for those vaccines. But the Novavax process may not move so speedily: FDA says it needs additional manufacturing and product information before an EUA can be issued. The U.S. Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices would also need to make a recommendation for who should receive the vaccine, and that committee has not yet scheduled a meeting.

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