FDA Correct to Turn Down Proposed Half-Dosing of Moderna Vaccine, Experts Say

The FDA made the right call in strongly advising against using a half-dose regimen of Moderna’s COVID-19 vaccine to stretch supply and vaccinate more Americans, members of the agency’s vaccine advisory panel told FDAnews.

Paul Offit, director of the Children’s Hospital of Philadelphia’s Vaccine Education Center, lauded the agency’s decision to urge healthcare providers to stick with the authorized double-dose administrations for both Moderna’s and Pfizer/BioNTech’s vaccines instead of trying different dosing schedules.

The FDA’s recommendation late Monday night (DID, Jan. 5) came in response to a strategy proposed by Moncef Slaoui, chief adviser of HHS’ Operation Warp Speed, aimed at vaccinating more people with Moderna’s vaccine by halving the dosing regimen for patients age 18 to 55. The strategy, which was put forward as the government’s vaccination efforts move slower than anticipated, should not currently be considered due to a lack of data around a double half-dose schedule, the agency said, while Offit called it “a terrible idea.”

“It’s based on some phase 2 data that show that participants inoculated with 50 micrograms of messenger RNA had a similar immune response to those who were given 100 micrograms,” Offit told FDAnews. “It assumes that if you have that immune response, that you’ll be protected. You don’t know that. That’s why you do phase 3 trials. If we knew that that level of immune response was protective, then you wouldn’t even need to do phase 3 trials. We do them because you have to prove in fact that it is protective.”

Offit stressed the fact that no phase 3 study has been conducted for a double half-dose regimen of either Moderna’s or Pfizer’s vaccines, which have both been granted Emergency Use Authorization by the FDA. A late-stage trial would be absolutely necessary to know for sure that such a regimen was effective in conferring protection against the virus, he said, and to date no such trial has been conducted to evaluate two half-doses.

“We have two excellent vaccines, so mass produce them, distribute them and administer them. That should be the focus, not on trying to figure out how to get away with fewer doses or a lesser quantity of each dose,” he advised. “We don’t have any data to support that. Do the next hard part, which is vaccination. Do that.”

Another advisory panel member, Cody Meissner, chief of Tufts Children’s Hospital’s Division of Pediatric Infectious Disease, also voiced support for the agency’s position not to try different dosing regimens without sufficient data. Doing so could damage the already fragile public trust in vaccines, he contended. 

“I understand the argument, that is you will then be able to vaccinate a larger number of people, but the other question I’d ask is what happens if it doesn’t work as well? Then people are going to have less willingness to accept the vaccine under any condition, and so I think there are lots of reasons why it would not be advisable to look at a change in the schedule,” he told FDAnews. “I would be a little bit uncomfortable with trying to change the dosing regimen that we know works unless we have another [phase 3] trial that shows it’s beneficial.” 

Meissner pointed out that Johnson & Johnson (J&J) will likely file for Emergency Use Authorization (EUA) soon, which means a third vaccine option could reach the American public in early 2021. J&J said yesterday that it anticipates filing for an EUA next month and should have enough data near the end of January. The vaccine would significantly help to simplify the vaccination process, as it only requires a single shot compared to Pfizer/BioNTech’s and Moderna’s double-dose vaccines. Additionally, it can be stored at standard refrigerator temperatures. J&J believes it will be able to manufacture more than 1 billion doses by the end of the year.

The administration has been under fire for failing to meet its goals of vaccinating 20 million people by the end of 2020, with only 4.56 million having been given their initial shots and 15.4 million doses distributed as of Monday morning. Despite the shortcomings of the government’s vaccination initiative so far, Anthony Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), expressed hope that efforts can pick up as the new year progresses.

“We’re not where we want to be. We’ve got to do much better, but let’s give it about a week or two into January to see if we can pick up momentum that was slowed down by the holiday season,” Fauci said in an interview Sunday. “Hopefully we’ll pick up some momentum and get back to where we want to be with regards to getting it into people’s arms.”

HHS declined to comment on the FDA’s decision. — James Miessler