Vaccine-producing partners Pfizer and BioNTech announced Monday that they had completed their application to the US Food and Drug Administration for authorization of their omicron BA.4/5 bivalent booster doses, which the Biden administration plans to distribute from in early September.
The request follows FDA guidance in late June directing vaccine manufacturers to prepare second-generation COVID-19 booster doses for the fall that target both the original version of SARS-CoV-2 and BA.4/BA.5, two subvariants of omicron. that share the same spike protein. Currently, BA.5 is the dominant variant in the world and in the US, where it accounts for 89 percent of infections, according to the latest estimates from the Centers for Disease Control and Prevention.
FDA Reinforcement Guide
The FDA’s guidance was based on the advice of its committee of independent vaccine advisors, who at a June meeting felt that a bivalent vaccine targeting BA.4/5 offered the best chance of improving efficacy against circulating variants. currently. Current COVID-19 booster doses, which target only the original SARS-CoV-2 strain, remain highly effective against severe illness and death from COVID-19, but have been losing efficacy against infection amid of a rapid succession of variants and subvariants of omicrons.
In some preliminary databivalent vaccine designs appeared to outperform single-target vaccines, offering broader protection against a range of variants. And, with BA. With 4/5’s undisputed reign as the dominant variants, FDA advisers felt it was reasonable to target second-generation boosters at the forefront of SARS-CoV-2 evolution.
The only problem is that vaccine manufacturers have little data on booster designs targeting BA.4/5. At the FDA advisory meeting in June, Pfizer-BioNTech and Moderna relied heavily on bivalent booster data targeting BA.1, the original omicron that was ramped up in January and is no longer in circulation. Those bivalent boosters targeting BA.1 are the most advanced in development. Vaccine makers seemed to assume that they would be the baseline boosters for this summer and fall, before an anticipated winter surge, which would likely be driven by an omicron subvariant.
Last week, the UK announced that it was the first to approve bivalent reinforcement targeting Moderna’s BA.1, which generated a strong response against BA.4/5 in clinical trials. Moderna is also planning supply of booster doses targeting BA.1 to the EU.
But, the Biden administration scrapped the idea to authorize a bivalent booster targeting BA.1 this summer, rather than push for an even faster fall launch of the more up-to-date BA.4/5 targeting boosters. However, the BA.4/5 boosters are still in the early stages of development; there are no clinical trial data on its efficacy and safety.
In June, the FDA told manufacturers that they could use data from their BA.1-targeted booster as part of the authorization application for their BA.4/5-targeted boosters. In addition, they could provide preclinical data, such as animal data.
In an email exchange with Ars on Monday, Pfizer noted that it only had efficacy data on its BA.4/5 bivalent booster of mice. In eight mice, the bivalent BA.4/5 boost generated about a 2.6-fold increase in neutralizing antibody levels against the BA.4/5 subvariants compared with the current boost of carriers. The companies submitted those mouse data to the FDA in June. In an email to Ars, Pfizer indicated that it had not collected any new preclinical efficacy data since then. It is not clear how reinforcement directed at BA.4/5 compares with reinforcement directed at BA.1.
In a joint news release, Pfizer and BioNTech noted that a human clinical study to assess safety, tolerability, and immune responses is “expected to begin this month.”
“Given the ongoing evolution of SARS-CoV-2 and its variants, it is of great importance that vaccines can be quickly tailored to the major Omicron lineages in circulation,” BioNTech CEO and co-founder Ugur Sahin said in the comments. Press releases. “Less than three months after the FDA provided its guidance for adapted vaccines in the US, we are ready to ship the first doses of our Omicron BA.4/BA.5 adapted bivalent vaccine, pending regulatory approval.” , to provide people in the United States with the ability to get a boost tailored to the currently most dominant strain of the virus.”
Biden officials hope the FDA clearance will go through quickly. Last week, White House COVID-19 response coordinator Ashish Jha told NBC News that the new reinforcements are expected to be available “within a few weeks.”
“I think it will be available and all Americans over the age of 12 will be eligible to receive it,” Jha said.
Critics of the move, including pediatrician Paul Offit, director of the Center for Vaccine Education at Children’s Hospital of Philadelphia and a member of the FDA’s advisory panel, fear that data from clinical trials will delay implementation nationwide. They note that it is not yet clear whether a BA.4/5-targeted vaccine will offer a clinically meaningful improvement over current boosters or BA.1-targeted boosters, for which there are already clinical data.