WASHINGTON (NYTIMES) - In documents released Tuesday (Oct 12), Moderna argued that the Food and Drug Administration (FDA) should authorise a half-dose of its coronavirus vaccine as a booster shot for recipients at least six months after the second dose, citing evidence that the vaccine's potency against infection wanes over time.
The agency noted in its own analysis that, overall, available data show that Moderna and the other vaccines "still afford protection against severe Covid-19 disease and death in the United States".
Moderna cited the rate of breakthrough infections, "real world evidence of reduced effectiveness against the Delta variant", and falling levels of neutralising antibodies from its vaccine six to eight months after a second dose.
The company said its clinical trial studies showed that a third injection boosted antibody levels - one measure of the immune system's response - higher than what they had been before the second dose.
The documents were released by the FDA before a two-day meeting of the agency's advisory committee, scheduled for Thursday and Friday. In its own briefing document for the committee, also released Tuesday, the FDA summarised the data without taking a position.
The committee is expected to vote on whether to recommend emergency authorisation of boosters of Moderna's and Johnson & Johnson's vaccines. While the panel's votes are not binding, regulators typically follow them.
Moderna did not try to argue that its vaccine is waning now against severe disease or hospitalisation, and the existing data does not appear to support that claim. That distinguishes Moderna's application from Pfizer-BioNTech's last month.
In its document, the FDA said, "Some real world effectiveness studies have suggested declining efficacy of Moderna Covid-19 vaccine over time against symptomatic infection or against the Delta variant, while others have not."
The agency said "there are many potentially relevant studies", and it has not independently reviewed the underlying data or conclusions of each one.
The FDA and the Centres for Disease Control and Prevention (CDC) decided to authorise boosters for many but not all Pfizer-BioNTech vaccine recipients. The eligible include those who are 65 or older, who live in long-term care facilities, who have underlying medical conditions or who are at higher risk of exposure to the virus because of their jobs or institutional settings. The last group includes healthcare workers, teachers and prisoners.
In the document released on Tuesday, the FDA proposed the outside experts consider essentially the same eligibility groups for Moderna recipients. But people familiar with the deliberations said that federal officials may also ask the committee to consider broadening eligibility for boosters of both vaccines to include more middle-aged people.
Moderna said it compared using a full dose and a half-dose as a booster and found that a half-dose boosted antibody levels well with lower risks of adverse side effects. It also tried to make a point about conserving limited supplies, saying a half-dose "would result in a substantial increase in the world wide supply" of its vaccine.
Several independent studies have tried to estimate how long Moderna's two-dose vaccine remains effective against mild, moderate and severe Covid-19. One looked at Covid-19 cases last summer among more than 15,000 volunteers in Moderna's clinical trial, some of whom had been vaccinated a full year earlier.
Researchers compared cases of Covid-19 in July and August among trial participants who had been fully vaccinated between July and October last year with cases among those who were fully vaccinated between December last year and March this year.
Those who got vaccinated later had a 36 per cent lower rate of Covid-19 disease. But Dr Hana M. El Sahly, a professor of molecular virology at Baylor College of Medicine and one of the lead researchers, said the study did not find a statistically significant difference between the two groups in cases of severe Covid-19 - of which there were only 19.
Overall, she said, "the findings do not indicate that a booster is needed". The study was backed by the National Institutes of Health, researchers said.
Another recent CDC study reviewed case files of nearly 3,700 patients in 21 different hospitals from March to August. Researchers found that of the three vaccines available in the United States, Moderna's vaccine held up best over six months.
The researchers said that Moderna was 93 per cent effective against hospitalisation, compared with 88 per cent for Pfizer and 71 per cent for Johnson & Johnson. Pfizer's efficacy dropped significantly after four months, to 77 per cent, while Moderna's basically held steady, they said.
Given the dearth of data showing that Moderna's protection weakens against severe disease, the committee's deliberations about boosters for Moderna recipients will likely revolve around other key questions.
First, is there a need to "harmonise" the US' booster strategy, making recipients of all three vaccines eligible even if they keep their potency for different periods of time? Some federal officials argue that with many Pfizer recipients already receiving boosters, the answer is yes.
"We're in this very complicated situation right now: People are going into pharmacies or places where vaccines are available and saying, 'I want my third dose of Moderna, or I want my second dose of J & J," said Dr H. Cody Meissner, an infectious disease expert at Tufts Medical Center who serves on the FDA panel. "I don't think anyone has much doubt that we will need a booster dose for these vaccines. What we don't know is, how urgent is the need?"
Another question is whether Moderna will eventually wane against severe disease. Some booster advocates argue that Moderna is following the same path as Pfizer's vaccine, just more slowly, because its initial dosage is significantly stronger, and the interval between the first two shots is longer.
Committee members are also expected to debate whether Moderna recipients should be given a booster simply to protect them against the risk of mild or moderate disease, or to try to disrupt transmission of the virus.
"The fundamental issue is, what are we trying to do?" Dr El Sahly said. "Both Moderna and Pfizer seem to have waned when it comes to mild to moderate disease, especially with the Delta variant. So if that's the goal, a booster is needed. If we want to prevent only severe disease that lands people in the hospital, that's a different mathematics."