The unfolding dosing controversy for COVID vaccines
Pressure is mounting to loosen up on the time between doses, but FDA is sticking to plan A
Pressure is mounting to loosen up on the time between doses, but FDA is sticking to plan A.
The one dose versus two controversy for COVID vaccines has a few twists left, with the incoming Biden administration departing from FDA’s conservatism in favor of giving more people their first shot sooner. While FDA is digging its heels in, it’s becoming more of a lone voice as more countries consider the raging pandemic an emergency worth breaking the glass for.
The Biden administration will not continue Operation Warp Speed’s policy of holding a second dose in reserve. It may hold some back, but the ratio will not be close to the one-to-one ratio of distributed-to-reserved vaccine that is the current policy, two sources who have been briefed by the Biden transition team told BioCentury.
Biden’s team is confident that manufacturing will keep up with demand for second doses, according to the sources, who wished not be named.
The position is in direct contrast to FDA’s announcement earlier this week that it would not bend from the authorized dosing schedules to stretch vaccine supplies further.
In a Friday briefing with reporters, FDA Commissioner Stephen Hahn reiterated the agency’s opposition to experimenting with single- or half-doses of vaccines that have been authorized in two-dose regimens. Other countries and the WHO this week indicated they are changing the dosing regimen to get the first dose to more people, or thinking of doing so.
The controversy sees scientific orthodoxy pitted against the urgency of the moment, layered on the orthogonal dilemma of retaining the public’s confidence in vaccines versus expanding protection across the population as fast as possible.
The issue is whether to only allow for use of regimens that have been proven safe and effective in clinical trials, as FDA believes, or whether to alter them to maximize the number of people who can obtain some level of immunity, either by stretching the interval between doses or by using lower doses than those authorized.
The agency’s concern with any deviation is that people will assume they are fully immunized when they are not, and that it runs a “significant risk of placing public health at risk,” according to the statement issued by Hahn and Center for Biologics Evaluation and Research (CBER) Director Peter Marks.
Those in that camp worry that if immunity wanes after a single dose before the next one is administered, the result would be that the population doesn’t receive proper protection and the vaccine supplies are effectively wasted.
Biden’s team has discussed and rejected the idea of withholding second doses altogether, according to the two sources.
The main argument for stretching doses is to stem the escalation of new cases, in particular given the emergence of variants with higher transmissibility. Those in this camp argue the clinical trial data contain enough information to believe sufficient protection is gained from the first dose, and that if supplies aren’t ramped up to allow the second dose per schedule, the delay won’t significantly dent the level of immunity.
According to modeling from scientists at the University of Toronto and Stanford University, 23-29% of COVID-19 cases could be averted by a flexible strategy that holds 10% of supplies in reserve and administers 90% during the first three weeks, and 50% thereafter.
What the two camps agree on is that decisions are being made on the basis of insufficient data, in a race against time that demands policymakers make risk determinations under pressure that will affect vast numbers of people.
However, it’s worth noting that the controversy doesn’t solve the major bottleneck in vaccinating the population. While the policy might double the number of people who could get vaccinated, the major problem at this point is deploying the vaccines that have already been distributed.
According to the CDC, 5.92 million people in the U.S. have received their first dose of vaccine, as of Jan. 7, less than 28% of the 21.4 million doses that were distributed. Globally, 18.6 million doses have been administered, according to data from the University of Oxford.
Former FDA Commissioner Scott Gottlieb and Operation Warp Speed Chief Scientific Advisor Moncef Slaoui have both proposed deviations from the authorized schedule that would allow more doses to be administered, citing the gravity of the escalating case numbers in the pandemic.
Gottlieb has called FDA’s approach unnecessarily conservative, and has advocated for holding a small reserve of vaccines, while administering as many as possible as soon as possible. His comments, made before the vaccine from Moderna Inc. (NASDAQ:MRNA) was authorized, were based on data from the clinical trial by Pfizer Inc. (NYSE:PFE) and BioNTech SE (NASDAQ:BNTX) indicating the first dose of Comirnaty (BNT162b2) is protective, coupled with confidence that Pfizer could manufacture sufficient doses to provide a second shot in time to meet the demand for the second vaccinations.
Slaoui has called for a different way to stretch supplies — halving the dose of the Moderna COVID-19 Vaccine (mRNA-1273). Slaoui cited Moderna’s clinical trial data showing that in individuals between the ages of 18 and 55, two doses of 50 μg elicited comparable immunity to two doses of 100 μg. Slaoui said Operation Warp Speed was in discussion with Moderna and FDA.
Phase IIa and Phase I data support the claim, based on neutralizing antibody titers. The 50 μg dose elicited 76% and 78% of the mean titers produced by the 100 μg dose in the two trials, respectively, at day 29, prior to the second dose. Those numbers rose to 100% and 84%, respectively, 28 days after the second dose.