Pfizer Completes FDA Solicitation for Fall Accelerators BA.4/5; the feds expect a dose in September.

Vaccine partners Pfizer and BioNTech announced Monday that they have completed a request to the U.S. Food and Drug Administration for approval of their bivalent booster doses of omicron BA.4/5, which the Biden administration plans to distribute from in early September.

The request follows FDA guidance in late June directing vaccine manufacturers to fall second-generation COVID-19 booster doses targeting both the original version of SARS-CoV-2 and BA.4/BA.5, two subvariants of omicron that have the same protein spike. BA.5 is currently the dominant variant globally 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 guidance on amplifier

The FDA’s guidance was based on recommendations from its independent vaccine advisory committee, which found at a June meeting that a bivalent vaccine targeting BA.4/5 offers the best chance for improved efficacy against currently available options. Current COVID-19 booster doses, which target only the original SARS-CoV-2 strain, are still highly effective against severe disease and death from COVID-19, but are losing efficacy against infection amid rapid change in omicron variants and subvariants.

In some preliminary databivalent vaccine designs appeared to outperform single-target vaccines by offering broader protection from a range of options. And, with a B.A. As the dominant 4/5 options, FDA advisors thought it prudent to target second-generation boosters at the leading edge 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’s June advisory meeting, Pfizer-BioNTech and Moderna relied heavily on data on bivalent booster doses targeting BA.1, the original omicron that grew in January and is no longer in circulation. These divalent accelerators, aimed at BA.1, are the furthest along in development. Vaccine manufacturers seem to have anticipated that they would be major boosters this summer and fall ahead of the expected winter surge, which is likely to be due to the omicron subvariant.

The UK announced last week that it had become the first approve the BA.1 bivalent amplifier from Moderna, which induced a strong response against BA.4/5 in clinical trials. Moderna also plans to supplying the EU with booster doses of BA.1.

But the Biden administration gave up on the idea of allowing a bivalent BA.1-oriented amplifier this summer, instead insisting on an even quicker fall release of more modern BA.4/5-oriented amplifiers. However, the BA.4/5 accelerators are still in the early stages of development; there is no clinical research data on their effectiveness and safety.

Preclinical data

In June, the FDA told manufacturers that they could use data on their BA.1-targeted booster as part of an authorization request for their BA.4/5-targeted boosters. In addition, they could provide preclinical data, such as animal data.

In an email to Ars on Monday, Pfizer said it only had data on the effectiveness of the BA.4/5 divalent enhancer from mice. In eight mice, the bivalent BA.4/5 booster produced an approximately 2.6-fold increase in neutralizing antibodies against the BA.4/5 subvariants compared to the companies’ current booster. The companies submitted the mouse data to the FDA in June. In an email to Ars, Pfizer said it has not collected new preclinical efficacy data since then. It remains unclear how the BA.4/5 targeting booster compares to the BA.1 targeting booster.

In a joint press release, Pfizer and BioNTech noted that a human clinical trial to evaluate safety, tolerability and immune responses “is expected to begin this month.”

“Given the continuous evolution of SARS-CoV-2 and its variants, it is critical that vaccines can be quickly adapted to Omicron’s main circulating lines,” BioNTech CEO and co-founder Ugur Sahin said in a press release. “Less than three months after the FDA issued guidelines for US-adapted vaccines, 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 US with the possibility of receiving a booster adapted to the most dominant strain of the virus at present.’

Biden officials expect FDA approval to go quickly. Ashish Jha, the White House’s COVID-19 response coordinator, told NBC News last week that the new accelerators are expected to be available “in a few weeks.”

“I believe it will be available, and every American over the age of 12 will be eligible for it,” Jha said.

Critics of the move, including pediatrician Paul Offitt, director of the Center for Vaccine Education at the Children’s Hospital of Philadelphia and a member of an FDA advisory panel, worry that data from clinical trials will lag behind nationwide rollout. They note that it remains unclear whether a vaccine targeting BA.4/5 would provide a clinically meaningful improvement over current boosters or boosters targeting BA.1, for which clinical data are already available.