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0104 FDA rebuffs
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FDA says don’t mess with dosing schedules for COVID vaccines

Jan 5, 2021 | 2:32 AM GMT

FDA has come down squarely on the side of evidence-based medicine, and conservative policy, regarding vaccine dosing, countering proposals that have been floated to reduce or spread out vaccine doses to make supplies go further.

In a statement issued Jan. 4, FDA Commissioner Stephen Hahn and Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), said the agency wants to “remind the public about the importance of receiving COVID-19 vaccines according to how they’ve been authorized by the FDA” to achieve the level of protection in the clinical trials that supported their emergency use authorization.

The statement rebuffs proposals from prominent figures including Operation Warp Speed Chief Scientific Adviser Moncef Slaoui, who touted the idea of providing half the dose (50 μg) of the Moderna Inc. (NASDAQ:MRNA) mRNA-1273 vaccine in two shots, instead of the 100 μg dose that was authorized, to double the number of people being immunized, based on the level of protection seen in clinical trials.

Slaoui made the statements on CBS News on Sunday. He said that while changing the dosing regimen without any data “would not be responsible,” the Moderna clinical trials supported the idea. “We know that for the Moderna vaccine, giving half the dose to people between the age of 18 and 55, two doses, half the dose, which means exactly achieving the objective of immunizing double the number of people with the doses we have. We know it induces identical immune response to the 100 μg dose and, therefore, we are in discussion with Moderna and with the FDA,” said Slaoui.

Former FDA Commissioner Scott Gottlieb has also argued for tinkering with the dosing, arguing that Operation Warp Speed’s decision to hold half of the U.S. vaccine supply in reserve to ensure availability of the second dose was overly conservative. Gottlieb said a small reserve should be maintained while as many first doses as possible are administered. His recommendation (made prior to the Moderna EUA) was based on data indicating that the first dose is protective, coupled with confidence that Pfizer Inc. (NYSE:PFE) will be able to manufacture sufficient doses of Comirnaty (BNT162b2) to provide a second shot in time to meet demand for second vaccinations. 

Hahn and Marks said FDA had been following discussion around these proposals, and suggestions of mixing and matching vaccines. 

“These are all reasonable questions to consider and evaluate in clinical trials,” they wrote in the Jan. 4 statement. “Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19.”

“What we have seen is that the data in the firms’ submissions regarding the first dose is commonly being misinterpreted,” stated Hahn and Marks.

The Phase III trials on which EUAs were based involved two doses for 98% of participants in the Pfizer and BioNTech SE (NASDAQ:BNTX) trial and 92% for the Moderna trial, with three- and four-week intervals between the doses for the two vaccines, respectively, said Hahn and Marks. Participants who didn’t receive two vaccines in this regimen were only followed for “a short period of time,” meaning that conclusions can’t be drawn “about the depth or duration of protection after a single dose of vaccine from the single dose percentages reported by the companies.”

Hahn and Marks called the idea of using single doses or administering less than the dose studied “concerning,” noting that the immunity conferred was associated with the duration of protection provided. They cited the potential for harm in that individuals “may assume that they are fully protected when they are not, and, accordingly, alter their behavior to take unnecessary risks.

Hahn and Marks said FDA would “continue to strongly recommend” that healthcare providers adhere to the authorized dosing schedules for each vaccine, until vaccine manufacturers “have data and science supporting a change.”

The U.K.’s Joint Committee on Vaccination and Immunisation (JCVI) has taken the opposite tack, allowing for a flexible dosing schedule to enable as many at-risk individuals as possible to receive the first dose. The U.K.’s MHRA  authorized a two-dose regimen with 4-12 weeks between doses for for COVID-19 Vaccine AstraZeneca (formerly AZD1222 ), the vaccine from AstraZeneca plc (LSE:AZN; NASDAQ:AZN) and the University of Oxford, though the trial protocol included a four-week interval.

The JCVI said the same first-dose prioritization should be given to Comirnaty, which MHRA authorized at the start of December.

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