FDA Panel Will Weigh In on Covid Boosters for This Fall. What’s at Stake.

The early case for the mRNA-based vaccines was that the adaptability of the technology meant they could be updated to match the virus as it evolved. The Tuesday meeting will test whether the case still holds, public health officials’ experience with mRNA-based vaccines grows, and the virus mutates faster than might have been expected.

The FDA meeting also comes amid new challenges to the hegemony of the Pfizer (ticker: PFE) and Moderna (MRNA) vaccines. Last week, Sanofi
(SNY) and GSK
( GSK
) released strong data on their bivalent, protein-based vaccine. Earlier this month, Novavax ’s (NVAX) protein-based vaccine received a nod from the FDA’s vaccine advisors.

A decision by the FDA to ask for updated vaccines for the fall would reaffirm the cases for Moderna and Pfizer—and the long-term value of their Covid-19 vaccine franchises against new challenges.

Moderna and Pfizer have said in recent weeks that their experimental boosters targeting the first Omicron strain, known as BA.1, elicit stronger immune responses against BA.1 than their original vaccines. White House officials have also argued that they need funding for the new bivalent vaccines.

The path the FDA’s advisors will take, however, isn’t predetermined. They will need to be convinced that the updated vaccines offer more protection than the currently authorized and approved versions of the vaccines.

“The question becomes here, can the companies clearly show evidence that if they give a booster dose with a BA.1 variant, that that is …clinically significantly better than boosting with just the ancestral strain,” says Dr. Paul Offit, a member of the FDA’s vaccines advisory committee and a professor of pediatrics at the Children’s Hospital of Philadelphia.

Documents the FDA posted on Saturday emphasize the complexity of the decision before the agency. While the committee itself will only be asked to vote on whether or not it recommends the “inclusion of a SARS-CoV-2 Omicron component” in booster vaccines, according to a voting question posted online by the agency, a briefing document by FDA staff lays out a broad range of possible outcomes. Those include that boosters and primary vaccines be updated, that only boosters be updated, that boosters be updated to include a component that targets BA.1, or that boosters be updated to target more recent Omicron strains.

Representatives from Moderna, Pfizer, and Novavax will speak at the Tuesday meeting. Moderna said in a news release in early June that its experimental bivalent vaccine, mRNA-1273.214, which targets BA.1 and the original Wuhan strain, induced a stronger neutralizing antibody response against BA.1 than its original booster.

On Saturday, Pfizer said that an experimental monovalent vaccine that targets BA.1, and an experimental bivalent vaccine that targets both BA.1 and the original Wuhan strain, both elicited a stronger immune response to BA.1 than its original booster. The experimental monovalent vaccine induced a stronger immune response to BA.1 than the bivalent vaccine.

The FDA briefing document posted Saturday said that the Moderna and Pfizer data both suggest that including an Omicron component in the vaccines improve the neutralizing antibody response to BA.1.

Countering the case for updated vaccines is the argument that continued boosts of the original vaccines result in what’s known as affinity maturation, a process that strengthens the antibodies produced by the immune system. “You do get a broadening of the response,” Offit says.

If the advisors do choose to update the vaccines, they will also need to decide which strain to recommend the manufacturers use. Moderna’s mRNA-1273.214 targets BA.1, the original Omicron strain, but BA.1 is effectively extinct, at least in the U.S. A newer strain, BA.2.12.1, is currently dominant in the U.S., but two more worrying strains, BA.4 and BA.5, are growing in prevalence.

BA.4 and BA.5 can evade antibodies induced both by prior infection and by vaccination with the original vaccine, according to a study published Wednesday in the New England Journal of Medicine. Moderna said last week that mRNA-1273.214 induced a strong neutralizing antibody response to BA.4 and BA.5, and Pfizer said Saturday that its updated vaccines neutralized those strains.

In their briefing document posted Saturday, FDA staff noted that no evidence exists regarding strain-specific vaccines designed to target more recent Omicron strains than BA.1.

Pfizer has said that it will be able to produce a vaccine targeting whatever strain the FDA asks for by the fall. “Following determination of an appropriate path forward by regulators, we’re confident we can produce and test—as directed by the FDA—a variant-specific vaccine, if needed, in an accelerated timeframe,” the company said in a statement to Barron’s.

Moderna has taken a different line. In early May, CEO Stéphane Bancel said the company can only make its original vaccine or mRNA-1273.214 for the fall.

“If we’re told …June 28 that we need a BA. 2-only booster, let’s say, …we cannot have it in August,” Bancel told Barron’s in early May. “It’s physically impossible.”

The company didn’t immediately respond when asked if that remains Bancel’s position, though Moderna hasn’t issued any contradictory statements in the weeks since.

The original vaccines from Pfizer and Moderna provided strong protections up until the rise of Omicron. “Omicron clearly crossed a line,” Offit says. Still, even as their ability to protect against mild illness eroded in the face of Omicron, the vaccines retained their ability to protect against severe illness.

“That’s the goal of this vaccine, to prevent severe illness,” Offit says. “It’s not to prevent all symptomatic illness.”

Another member of the advisory committee echoed that viewpoint of the vaccines’ purpose to Barron’s.

“It is unrealistic to think we are able to prevent all infections,” says Dr. Henry Bernstein, an advisory committee member and a professor of pediatrics at the Zucker School of Medicine at Hofstra/Northwell. “To be perfectly honest, we need to get the unvaccinated, vaccinated. I don’t think we’d have nearly as many variants develop if more people were vaccinated.”

Write to Josh Nathan-Kazis at josh.nathan-kazis@barrons.com