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Federal advisers on Thursday overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continued testing of this medicine.
The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.
The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.
Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.
FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.
“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”
In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee, spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.
Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% – 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.
The advisers and FDA staff also homed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.
Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel Thursday that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.
In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.
The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.
“These cases underscore the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise fact sheets and prescribing information for their vaccine to draw attention to CDC guidelines for post-vaccination monitoring and management of immediate allergic reactions.”
mRNA Vaccines in the Lead
An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.
In a December 15 commentary for Medscape, Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”
“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.
The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.