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A senior US Food and Drug Administration (FDA) official says Moderna\u2019s clinical trial on a new, potentially more effective flu vaccine<\/a> was a \u201cbrazen failure\u201d and that the FDA is now calling it into question.<\/p>\n The FDA unexpectedly refused to consider Moderna\u2019s application for a flu shot based on messenger RNA (mRNA) technology in a decision that experts say is already having a chilling effect on vaccine development.<\/p>\n Officials say the issue is the design of the study, in which control group participants over the age of 65 should have received a high-dose flu shot instead of a standard flu shot.<\/p>\n Outside experts say the reasons seem to go deeper.<\/p>\n \u201cIt\u2019s all pretext and obfuscation when the real agenda is rejecting conventional science and serving a predetermined anti-vaccine agenda,\u201d said Richard Hughes IV, a partner with Epstein Becker Green and law professor at George Washington University.<\/p>\n Dorit Reiss, professor of law at UC Law San Francisco, said \u201cpersonally humiliating a company is not a legitimate reason to refuse to review a submission\u201d, and the refusal needs to \u201caddress substantive reasons\u201d. Angela Rasmussen, an American virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan, says \u201cthey\u2019re just coming up with reasons to not approve mRNA anything, and they\u2019re going to eventually do it to all these vaccines\u201d.<\/p>\n Andrew Nixon, a spokesperson for the US Department of Health<\/a> and Human Services, said the concerns that mRNA and other vaccines are being targeted by officials were \u201cbaseless\u201d.<\/p>\n The senior FDA official who asked not to be named in a press conference with journalists on Wednesday said that the \u201cbrazen failure of Moderna\u201d to design the study differently \u201craises significant ethical concerns\u201d.<\/p>\n Even the way the FDA is communicating about the issue raises alarm, Reiss said.<\/p>\n \u201cNot identifying yourself tells me you are unwilling to stand behind the decision because you know it is weak, flawed and untenable \u2013 politically motivated, not substantially valid,\u201d she said. \u201cBeing anonymous here is a coward\u2019s act, and shows the government knows it has no case.\u201d<\/p>\n The vaccine application was rejected because it did not have an \u201cadequate and well controlled\u201d trial, with the control group lacking \u201cthe best-available standard of care in the United States at the time of the study\u201d, according to a letter signed by Vinay Prasad, director of the FDA\u2019s Center for Biologics Evaluation and Research (CBER).<\/p>\n Moderna says the FDA frequently weighed in on their process, and never objected to the study until now.<\/p>\n \u201cThis was an FDA-approved trial design,\u201d said Chris Ridley, spokesperson for Moderna.<\/p>\n When the Guardian asked whether the FDA approved the design, the official didn\u2019t answer directly, confirming that the FDA gave a \u201ca recommendation in writing\u201d to include a high-dose vaccine for older participants, \u201cbut of course, they did say if they don\u2019t follow the recommendation, it\u2019s important for patients to have informed consent\u201d.<\/p>\n At other points in the press briefing, however, the official characterized the FDA\u2019s stance in stronger terms.<\/p>\n \u201cWe told you not to run it in over 65,\u201d the official said of its directive to Moderna. \u201cYou didn\u2019t do what we told you, so go back to the drawing board.\u201d<\/p>\n In April 2024, Moderna said, CBER told the company in writing that \u201cwhile we agree it would be acceptable to use a licensed standard dose influenza vaccine\u201d in the control group, \u201cwe recommend you use a vaccine preferentially recommended for use in older adults\u201d, such as a high-dose vaccine. Such a move \u201cmay help inform ACIP\u2019s recommendation for the use of your vaccine in the older adult population\u201d, the FDA said, according to Moderna.<\/p>\n The Advisory Committee on Immunization Practices (ACIP<\/a>) and CDC<\/a> recommend the higher-dose vaccines when possible, though standard vaccines are recommended if higher doses aren\u2019t available.<\/p>\n Moderna included information about the decision to use the standard flu shot for all ages in the consent form that all trial participants signed, a plan with which FDA officials agreed, according to Moderna. It\u2019s highly unlikely that the FDA told Moderna not to proceed on a trial like this and the company did so, Hughes said.<\/p>\n \u201cIt\u2019s too risky for a manufacturer to simply run roughshod over agency guidance and continue down a path that very clearly is not in line with what was agreed to with the agency. What is more likely is that this FDA turned the tables at the 11th hour,\u201d he said.<\/p>\n The FDA last year only approved Covid shots from Novavax and Pfizer for certain groups of people. And instead of adding a warning label for a new Chikungunya vaccine after serious side effects were observed, the FDA revoked the license entirely, Hughes pointed out.<\/p>\n In the Moderna decision, Prasad overrode agency scientists who recommended review of the application, including a memo from David Kaslow, director of the vaccine office, according<\/a> to Stat News. The FDA official who refused to be named on Wednesday dismissed the reporting as \u201cgossip in the hallways of the FDA\u201d from \u201ca disgruntled person getting disproportionate coverage by reaching out and telling their version of the story\u201d.<\/p>\n Prasad\u2019s tenure at the FDA has been tumultuous<\/a>. He was fired<\/a> from the FDA in July before being reinstated, and the Wall Street Journal on Wednesday reported<\/a> that there are allegations of verbal and sexual harassment from Prasad at the agency.<\/p>\n Moderna could change its application to consider the vaccine for people from the ages of 50 and 64, the official said.<\/p>\n \u201cIt is entirely feasible that if they come back, maybe even show some humility and [say] that: \u2018Yes, we didn\u2019t follow your recommendation, these are the data we have, and let\u2019s just take a look at the 50 to 65 [sic] group, where there\u2019s a little more equipoise,\u2019 then the review team could say: \u2018We\u2019ll consider that cohort,\u2019\u201d they said.<\/p>\n Moderna did add a group of participants over the age of 65 who received the high-dose vaccine in the trial. But the FDA said that evidence wasn\u2019t robust enough to be considered for approval.<\/p>\n \u201cThey looked at immediate antibody response,\u201d the official said. \u201cPeople have been critical of using an antibody surrogate when you have the real-world outcome that is measurable.\u201d Antibody responses are frequently used in vaccine trials, especially for flu vaccines.<\/p>\n Nixon, the HHS spokesperson, said: \u201cModerna exposed participants age 65 and over to increased risk of severe illness by giving them a substandard of care against the recommendation of FDA scientists.\u201d<\/p>\n Rasmussen didn\u2019t find these arguments compelling: \u201cIt just seems like they couldn\u2019t really find anything that suggested that there would be a problem in the overall trial, so you focus on the older people.\u201d<\/p>\n