A committee of expert and independent advisers to the Food and Drug Administration voted overwhelmingly to authorize the two-dose Novavax COVID-19 vaccine on Tuesday, with 21 of 22 committee members voting in favor of the vaccine and one member abstaining.
Endorsement is only for a two-dose primary series in adults, not for boosters. The FDA is not required to follow the advice of its committee — the Vaccines and Related Biological Products Advisory Committee (VRBPAC) — but the agency typically follows its advice. If the FDA authorizes the vaccine, the Centers for Disease Control and Prevention will need to approve its use before it becomes available.
The decision on the Novavax vaccine, which is already authorized in dozens of other countries, is not straightforward in the US. The vaccine has some advantages over currently approved vaccines, but it has several downsides.
In terms of design, the vaccine follows a more traditional recipe than the two mRNA-based COVID-19 vaccines or Johnson & Johnson’s adenovirus vector-based design. Both designs are relatively new and work by delivering genetic code for the SARS-CoV-2 spike protein to our cells, which then translate the code. The Novavax vaccine, on the other hand, is a protein subunit-based vaccine that directly delivers the SARS-CoV-2 spike protein to cells along with an adjuvant – which is an additive used in vaccines to improve immune responses to the vaccine. In this case, the adjuvant is derived from saponin compounds found in Chilean soap tree, which have been used in FDA-approved vaccines previously.
Generally, the protein subunit vaccine design is tested and reliable; it is already used in vaccines against flu, whooping cough (pertussis) and meningococcal infection, for example.
Who would make it?
Novavax leaned heavily towards traditional design in its speech to the FDA. Now that we’re more than two years into the pandemic and mRNA vaccines are readily available in the US, most people who want to get vaccinated have already had their shots. This raises a key question of what role Novavax’s vaccine has left to play and how it warrants “emergency use” authorization given the availability of other vaccines.
The company has firmly focused its traditional injections on vaccines, which the CDC estimates at about 27 million. They may be wary of the more innovative mRNA vaccines, but they may ultimately be persuaded to be vaccinated if they offer an alternative that is perceived as more conventional, Novavax argued.
“Millions of Americans today still haven’t been vaccinated,” said Greg Poland, director of the Mayo Vaccine Research Group, who spoke on behalf of Novavax at Tuesday’s meeting. “For those individuals who are not fully vaccinated and are waiting for another option, having a vaccine platform that multiple stakeholders – including regulators, clinicians and the public – are familiar with can help mitigate some of the challenges we face today.”
While some committee members were skeptical that another option would influence resistant ones, the FDA’s top vaccine regulator, Peter Marks, appeared to buy it. “We have a problem with vaccine acceptance that is very serious in the United States, and anything we can do to make people more comfortable accepting these potentially life-saving medical products is something that we feel we are obligated to do. “, said Mark. He also noted that some Americans are not able to obtain mRNA vaccines due to adverse reactions, so protein-based ones would be a welcome new option.
Efficacy, variants and safety
Novavax’s vaccine had solid efficacy estimates in a clinical trial published in February in the New England Journal of Medicine. In the trial of more than 29,000 participants, the vaccine had an estimated overall efficacy of 90.4% against symptomatic COVID-19. Vaccine safety data suggest that it is generally safe and well tolerated, although there may be a link to rare cases of cardiac inflammation (myocarditis) seen with mRNA vaccines.
That said, the test was completed last year before delta and omicron (with all their subvariants) emerged. It is unclear how the vaccine’s effectiveness will resist these newer variants.
The only abstention vote on Tuesday — cast by committee member Bruce Gellin, head of global public health strategy at the Rockefeller Foundation — was related to the variant problem. “The data we heard today and saw today was impressive,” Gellin said, particularly against harsh results. “But we don’t know if that attribute remains relevant today … we really don’t know if it’s likely to be effective going forward and how long that protection might last.”
He clarified that he did not want to vote against the vaccine, but would only offer a conditional vote in favor given the limited data.
storage and manufacturing
The Novavax vaccine has an advantage over mRNA vaccines in terms of storage. The vaccine does not need to be stored frozen; instead, it can be kept at refrigerator temperatures.
But, Novavax has had major manufacturing setbacks, which could mean any future launches will be slow. Last summer, its Texas subcontractor, Fujifilm Diosynth Biotechnologies, stopped manufacturing the vaccine after the FDA encountered problems at the facility. Novavax then moved to the Serum Institute of India. The questions arose at the FDA meeting on Tuesday, with the agency noting that it effectively had to ignore some of the company’s clinical trial data because the manufacturing processes for the doses had changed over time.