Initial supplies of COVID-19 vaccines are obviously limited, even as drugmakers ramp up production, so governments are looking for ways to stretch their stocks. For Moderna’s mRNA-1273, that could mean reducing the dosing strength.
The U.S. government is considering halving the dose of Moderna’s COVID-19 vaccine, Operation Warp Speed chief Moncef Slaoui told CBS’ Face the Nation Sunday. The vaccine task force is in talks with Moderna and the FDA about implementing the idea, he said.
“We know that, for the Moderna vaccine, giving half of the dose to people between the ages of 18 and 55, two doses [at] half the dose … we know it induces identical immune response” to the currently authorized dose, Slaoui added.
Moderna declined to comment on potential ongoing regulatory discussions.
Currently, mRNA-1273 is authorized by the FDA in two injections at the 100 μg dose four weeks apart. Slaoui argued that reducing the dosing strength by half could cover twice as many people with the current supply. The U.S. has ordered a total of 200 million doses of the Moderna vaccine, with about 20 million earmarked for 2020.
Slaoui made that comment in response to a question about the U.K. government’s approval of a more spaced-out dosing schedule for AstraZeneca’s AZD1222 and Pfizer and BioNTech’s BNT162b2. Aiming to immunize more people with a first dose quickly, U.K. health authorities have allowed the gap between the two required doses—the initial plus a follow-up booster—to extend from four or three weeks to as much as 12 weeks for the AstraZeneca and Pfizer-BioNTech shots.
“It is a classic public health approach centered on doing as much good for as many people in the shortest possible timeframe, within the available vaccine supplies, against a background of immediate disease activity and still high population sero-susceptibility,” the country’s chief medical officers wrote in an open letter to U.K. physicians on Thursday.
While Britain’s top medical officials touted the arrangement as “much more preferable in public health terms,” the decision immediately drew criticism because prolonged dosing intervals weren't tested in the clinical trials supporting the vaccines’ emergency authorizations.
BNT162b2, for example, was tested in two doses three weeks apart, and its U.S. authorization reflects that schedule. “There are no data to demonstrate that protection after the first dose is sustained after 21 days,” Pfizer stressed in a statement.
“Pfizer believes it is critical health authorities conduct surveillance efforts on any alternative schedules implemented and to ensure each recipient is afforded the maximum possible protection, which means immunization with two doses of the vaccine,” the New York pharma added.
Peter Bach, director of Memorial Sloan Kettering’s center for health policy and outcomes, also suggested that the U.K. could essentially run real-world tests of the dosing regimens. Researchers could randomize the healthcare providers receiving the vaccines and compare the efficacy of different dosing regimens.
And what I have read in terms of the risks of this approach are data free arguments about how delaying or even missing the second shot is not that big a deal. Why don’t we study this question. We have a bunch of hcw’s getting 1st shot. Randomize them to 2nd vs delay.— Peter B. Bach, MD (@peterbachmd) December 30, 2020
AZ’s AZD1222 was originally developed in a prime-booster regimen given 28 days apart. But the company pointed to an exploratory analysis, which showed a 73% efficacy for a wide range of dosing intervals up to 12 weeks, which appeared to be better than the 62% for the 28-day regimen. Earlier immunogenicity data also suggest higher levels of antibodies the longer the dosing interval, up to 12 weeks.
“There is also emerging/preliminary data that suggest increased immunogenicity up to 12 weeks dose interval may also lead to increased efficacy,” an AZ spokesperson said.
“Further analyses are expected from the ongoing Oxford-led trials in the coming weeks and we are currently discussing with regulators how best to investigate this further, either through our existing trial program or as a new clinical trial,” the spokesperson said.
AstraZeneca CEO Pascal Soriot has said that updated data will prove a “winning formula” for AZD1222 with efficacy that’s “up there with everybody else.”
But Slaoui rejected the U.K. approach during his CBS interview. Changing the dosing regimen without data “would not be responsible,” he said. Waiting up to three months to inject the second dose could leave people with “incomplete immunity, waning immunity, maybe even the wrong kind of immune response induced,” which may not be timely corrected by the second dose, he said.