VRBPAC recommends addition of Omicron-component to future boosters

Regulatory NewsRegulatory News
| 28 June 2022 | By Ferdous Al-Faruque 

A panel of experts recommended the inclusion of an Omicron component in future COVID-19 vaccine boosters in the United States. Public health officials suspect another surge in COVID-19 cases this fall and are considering boosters with an updated strain composition in hopes that vaccine targeting a more recent strain of the virus will be more effective.
 
FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) met on 28 June to discuss whether the agency should recommend changes to vaccine composition for the fall. Public health officials, including representatives of FDA and the Centers for Disease Control and Prevention (CDC), noted that Omicron, especially subvariant BA.2, is the dominant strain of the virus in the US with subvariants BA.4 and BA.5 quickly gaining ground.
 
Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), in his opening remarks said FDA wanted to hear from the VRBPAC experts on whether a variant-specific booster is warranted considering the expected surge in new COVID-19 cases in the fall. He noted the agency needs feedback early so that manufacturers had sufficient time to file their applications and start production. Ultimately, the committee agreed 19-2, with no abstentions, that an Omicron component should be included in upcoming COVID-19 boosters.
 
“Over the past 2 years, we’ve seen waves of COVID-19 hospitalizations. Those have been associated with an evolution in the virus and the virus has rapidly evolved through several different variants that have come and go,” Marks said.

However, he noted that the vaccines’ effectiveness has waned over time, especially in older individuals, and given the virus’ evolutionary drift. Marks also pointed out that the agency anticipated the need for updating the strain composition of COVID-19 vaccines via immuno-bridging before authorizing the first booster doses.
 
With the rise of the Omicron variant and its multiple subvariants, including BA.4 and BA.5, the need to update the vaccines’ composition has become clearer.
 
Henry Bernstein, a pediatrician at Cohen Children’s Medical Center, and Paul Offit, a pediatrician at the Children’s Hospital of Philadelphia, were the only two who voted against the inclusion of an Omicron component for future boosters. They argued that there is no assurance that the current dominant variant will still be the dominant variant in the fall.
 
“I'm still not comfortable enough that we have the information that makes us essentially support this new product and I don’t think it’s fair to ask people to take a risk, which is true with any vaccine we get, if we don’t feel comfortable with the level of protection that we’re likely to get by including Omicron,” said Offit.
 
Predicting the future
 
Justin Lessler, an epidemiologist at the University of North Carolina, presented projections from the COVID-19 Scenario Modeling Hub that looked at potential cases and deaths between March 2022 and March 2023 based on current data and a new more virulent variant of SARS-CoV-2. The group of academic epidemiologists projects that COVID-19 deaths during the one-year period will range from 95,000 to 211,000.
 
Lessler cautioned the data are projections, not forecasting, because a number of variables could change including unforeseen new variants, change in public behavior and more. He specifically noted that the emergence of Omicron led the group of researchers to reconsider how they viewed the virus and realize that variants with very high immunoescape were possible.
 
“We don’t pretend we can say what a new variant will look like. We try to pick some scenarios that bound reasonable possibilities, but we don’t capture everything,” said Lessler. “We completely underestimated how Delta could be. But with Omicron, based on early information from South Africa we were able to do a pretty good job of what that could be once we had that early data on its epidemiology, but we didn’t have a crystal ball.”
 
Arnold Monto, VRBPAC chair and an epidemiologist at the University of Michigan empathized with Lessler noting how difficult it is to predict what the future of the virus holds.
 
“That’s the problem because we’re being asked, more or less, to have a crystal ball today,” Monto said to Lessler.
 
Industry presentations
 
During the industry presentation segment of the meeting, Kena Swanson, vice president of vaccine research and development at Pfizer, argued that FDA should authorize new variant-specific mRNA boosters based on preclinical data.
 
"The data shows Omicron-modified vaccines neutralize BA.4 and BA.5, though to a lesser extent than BA.1. These data are consistent with published observations of breakthrough BA.1 infections,” she said. “With the likelihood that Omicron BA.4 or BA.5 may become the dominant sub-lineage in the US, we need a more rapid mechanism other than clinical evaluation to enable the availability of variant-modified vaccines in the US to stem the health crises caused by emerging variants."
 
Swanson said that Pfizer’s immunogenicity studies of monovalent and bivalent vaccine boosters have reasonably predicted neutralization responses in both vaccine-naive and vaccine-experienced human patients. The responses were similar to what was seen in preclinical studies with mice on those same vaccines.
 
"These data suggest that going forward and based on the already extensive clinical experience with variance-modified vaccines which use the same mRNA platforms and are produced with the same process as the current vaccine, provision of preclinical immunogenicity data and appropriate [chemistry, manufacturing, and control] data package could enable a more rapid response to the changing variance landscape,” said Swanson. “If such a process were implemented, responses to future waves could be substantially accelerated. Vaccines that optimally match circulating strains could be better enabled both by the established body of clinical data and speed in which mRNA vaccines can be produced."
 
She noted that while current vaccines have been effective in preventing severe Omicron illness in the general population, data shows effectiveness against hospitalization wanes about 9 months after the second dose and it’s unknown how well the vaccine does six months after the third dose.
 
“Given the burden of Omicron on the health care system and society, and the erosion of protection of current vaccines of Omicron over time it may be time to consider an update to the current vaccine,” Swanson added.
 
During the meeting Swanson also presented late breaking preclinical data that Pfizer submitted to the panel that morning showing BA.4 and BA.5 specific vaccines that have shown to be effective in mice.
 
Steven Hoge, president of Moderna, also presented data from his company’s Omicron-targeted bivalent booster, which he said has the potential to provide improved protection against SARS-CoV-2 in anticipation of a surge of COVID-19 cases this fall. He said the data met prespecified primary and key secondary objectives including superior neutralizing titers against BA.1 and significantly higher titers against the ancestral strain with a favorable safety and tolerability profile.
 
"We also demonstrated higher binding antibodies against the prior variants of concern - Alpha, Beta, Gamma and Delta; robust neutralizing titers against BA.4 and BA.5 including among adults over the age of 65. And we previously demonstrated a more durable antibody response with our bivalent platform,” he said. "Based on these data, we will be completing our regulatory submission within the next two weeks, and pending authorization, large-scale supply of the bivalent Omicron vaccine could be available in late July and early August."
 
Hoge noted that Moderna has been producing hundreds of millions of doses of the bivalent vaccine at risk anticipating a positive verdict from FDA to allow their booster on the market. If the company was asked to produce a BA.4- and BA.5-specific vaccine, the development phase would take three months he noted and with a quick FDA submission process, the company could get those vaccines out the door in late October or early November.
 
Similarly, Pfizer said they could get their variant-specific vaccines on the market by early October.
 
Gregory Glenn, president of research and development at Novavax also presented data on his company’s work on developing an Omicron-specific vaccine. Ultimately, however, Jerry Weir, director of viral products at the Office of Vaccine Research at CBER noted that while companies have submitted data on Omicron-specific vaccines to FDA, the data has not yet been independently verified.
 
“We’re not here evaluating these vaccines per se, we’re trying to use their information to help guide a strain composition decision for all [COVID-19] vaccines,” he said.

“The immunogenicity data from candidate modified vaccines containing an Omicron BA.1 component… indicate an improved statistically superior Omicron/B.A1-neutralizing antibody [geometric mean titer] compared to the prototype vaccine from each manufacturer, for all candidate vaccines tested, and that includes both monovalent and bivalent candidate vaccines,” Weir added.
 
The bottom line he said is that the agency thinks Omicron-specific vaccines have indicated they are effective specifically against the strain.
 
Despite the promises the vaccines may hold, Weir also noted there are a number of challenges that public health officials including FDA need to take into consideration if they decide to consider allowing variant-specific vaccines on the market. They include deciding on the vaccine formulation which could be monovalent, multivalent or another type of variant-specific vaccine. He also noted it will be crucial to conduct vaccine effectiveness studies, take into consideration that protective antibody titers for sub-lineages may be significantly different from the previous strain, and the programmatic and operational challenges of making COVID-19 vaccine modifications.
 
Weir also noted that while the strain composition process for COVID-19 vaccines will benefit from further refinement it will require improved coordination and consensus regarding the types of data needed for decision-making.
 
“I will remind you that the parallel track of influenza strain selection, which works very well, was a process that was honed over many, many years,” said Weir. “This is a very different virus, so we probably have a lot of work to do on this strain selection process for COVID vaccines.”

 

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