After the Food and Drug Administration pulled its authorization of two COVID-19 antibody drugs because the treatments are highly unlikely to work against the omicron variant, Gov. Ron DeSantis of Florida misleadingly claimed the decision had been made “without a shred of clinical data” to support it. There may not be data from patients, but lab studies strongly suggest the treatments will not help omicron-infected people.
On Jan. 24, the FDA announced it was no longer authorizing two COVID-19 monoclonal antibody drugs in the U.S., given evidence that they are “highly unlikely” to work against the now-predominant omicron variant. The Centers for Disease Control and Prevention estimates omicron accounts for 99.9% of coronavirus infections in the country, as of Jan. 22.
“This avoids exposing patients to side effects, such as injection site reactions or allergic reactions, which can be potentially serious, from specific treatment agents that are not expected to provide benefit to patients who have been infected with or exposed to the omicron variant,” the FDA said in a press release explaining its decision.
In statements, the manufacturers of both antibody drugs in question — Eli Lilly and the biotech company Regeneron — said they agreed with the FDA and found the decision appropriate.
The agency said that it would allow the use of the drugs again if another variant comes along that is “susceptible to these treatments,” and pointed health care providers to treatments that are expected to be effective against omicron. Those include two newly authorized antiviral pills, the antiviral remdesivir, and a different monoclonal antibody, Vir Biotechnology and GlaxoSmithKline’s sotrovimab — although some of these are in short supply.
The state of Florida and its Republican governor, however, were critical of the agency’s move, demanding in a Jan. 24 press release that the government “reverse its sudden and reckless decision” and saying that the state had had to cancel more than 2,000 antibody treatment appointments for the following day.
“This abrupt and unilateral action by the Biden Administration will prevent access to lifesaving treatments for Floridians and Americans,” the release reads, failing to mention that the reason the FDA was suspending its authorization of the drugs was a lack of effectiveness.
“Without a shred of clinical data to support its decision, the Biden Administration has revoked the emergency use authorization for lifesaving monoclonal antibody treatments,” DeSantis then wrote in a Jan. 25 tweet. “Floridians have benefited from the state’s treatment sites and their access to treatment shouldn’t be denied based on the whims of a floundering president,” he added.
But DeSantis, who has long advocated antibody treatments — and has not always promoted vaccines with the same vigor — misleads by focusing solely on clinical data. While there may not be studies in people demonstrating that the antibody treatments are now useless, there’s an abundance of other data, including from the companies, that suggest these drugs have little, if any, ability to fight off the omicron variant.
Moreover, much of that evidence has been apparent for a month. The National Institutes of Health’s COVID-19 treatment guidelines have cautioned since Dec. 23 that the drugs are unlikely to be effective against omicron, and advised providing them only when 20% or more of a population is expected to be infected with a different variant, with the “understanding that treatment would be ineffective if they are infected with the Omicron variant.”
On Jan. 19, given the pervasiveness of omicron, the agency revised its guidelines further to recommend against giving the drugs entirely, since “real-time testing to identify rare, non-Omicron variants is not routinely available.” Multiple states, including Florida, have nevertheless continued to provide the drugs to large numbers of people.
Since September, the federal government has been supplying COVID-19 monoclonal therapies to states, based on the COVID-19 caseload and how much a locale has been using the drugs. State and territorial health departments then decide where to send the treatments.
This week, Florida was allocated 3,216 treatment courses of sotrovimab — the only monoclonal that likely remains effective against omicron — which was more than any other state, except for California and Texas. But those doses aren’t enough to replace the loss of the omicron-resistant drugs drugs. Last week, for example, Florida received twice as many treatment courses of the Regeneron and Eli Lilly therapies, combined, as sotrovimab.
Omicron-Resistant Antibody Drugs
The drugs in question are synthetic antibodies that include Regeneron’s REGEN-COV, which is a combination of the antibodies casirivimab and imdevimab, and Eli Lilly’s combo of bamlanivimab and etesevimab. Both antibody treatments target the spike protein of the SARS-CoV-2 virus and can prevent it from entering cells — or at least they could for past versions of the virus.
Earlier clinical trials showed the antibody cocktails, which are either infused intravenously or injected under the skin, reduced the risk of hospitalization or other negative outcomes in high-risk outpatients, leading the FDA to authorize them for non-hospitalized patients with mild to moderate COVID-19 who are at high risk for developing severe disease. As with any COVID-19 treatment, the monoclonals are not a substitute for vaccination.
But there’s virtually no reason to think those past results will hold against the highly mutated omicron variant. Because of its mutations, the shape of the omicron variant’s spike protein is different — and these particular antibodies can’t neutralize the omicron variant very well if at all, as numerous lab studies have shown.
Many of these studies tested whether the antibodies were effective in limiting infection of cells in a petri dish using viruses engineered to express coronavirus variant-specific spike proteins, or what are known as pseudoviruses. Such experiments can evaluate how well various antibodies fare against variant viruses, but are safer and faster to do than similar experiments using live, infectious virus.
A paper published in Nature by scientists in Hong Kong and at Columbia University, for example, found a dramatic reduction — more than 1,000 times — in the ability of the Regeneron and Eli Lilly antibodies to neutralize an omicron pseudovirus, compared with an ancestral pseudovirus. “Strikingly,” the authors wrote, all four of the tested combination drugs lost “substantial activity” against omicron, “likely abolishing or impairing their efficacy in patients.”
Several other unpublished papers that have not yet been peer-reviewed similarly found little or no neutralization activity of the antibodies used in the Regeneron and Eli Lilly cocktails against omicron pseudoviruses.
When tested against full-fledged, infectious omicron virus, the Regeneron and Eli Lilly antibodies also have failed. A Dec. 23 report published in Nature, for example, found all of the antibodies in those treatments, either individually or in combination as they appear in the cocktails, were “inactive” against an omicron virus isolated from a traveler returning to Belgium from Egypt.
Similarly, a Jan. 19 Nature Medicine study found the Regeneron and Eli Lilly antibody combinations used as treatments “lost all neutralizing activity” against an omicron virus taken from an infected American.
These findings are also consistent with what the companies have found.
“Evaluation of both pseudovirus and authentic virus confirm that they are not effective at treating the currently predominant Omicron variant,” Eli Lilly said in a statement of its antibody cocktail, adding that the company and the FDA “agree that it is not medically appropriate” to use the product.
In a statement to FactCheck.org, Regeneron called the FDA’s decision to limit the use of its drug “appropriate” and said that its previously effective cocktail “does not work against Omicron in lab tests, which tells us that unfortunately it is also not going to work in people infected with this variant.”
Both companies have other monoclonals that they say should work against omicron. Eli Lilly’s bebtelovimab is under review by the FDA for an emergency use authorization, while Regeneron is prepping to begin clinical testing of its candidate.
Clinical Data Loophole
DeSantis’ claim that there is no clinical data showing the Regeneron and Eli Lilly antibody treatments are ineffective is technically accurate, but he’s hiding behind that lack of data, rather than being transparent about the fact that all other available evidence to date strongly suggests the therapies are largely, if not entirely, useless.
The Florida Department of Health has made arguments similar to DeSantis’, citing a limitation mentioned in a study that it claims supports its position.
“Florida disagrees with the decision that blocks access to any available treatments in the absence of clinical evidence. To date, such clinical evidence has not been provided by the United States Food and Drug Administration (FDA),” the department said in a press release announcing the closure of the state’s antibody treatment sites following the FDA’s decision on the EUA.
“As stated in one of the pre-print studies cited on the NIH website, ‘despite observing differences in neutralizing activity with certain mAbs, it remains to be determined how this finding translates into effects on clinical protection against B.1.1.529.’”
But this is not the “gotcha” that it might appear to be. The senior author of that study, Dr. Michael S. Diamond, an infectious disease specialist and microbiologist and immunologist at the Washington University School of Medicine in St. Louis, told FactCheck.org that the cell culture findings should be confirmed in animals, but that some of that work has already been done. And pending confirmation isn’t a reason to ignore the existing data.
Diamond’s study, which is now published in Nature Medicine, is the one that found the Regeneron and Eli Lilly antibody cocktails “lost all neutralizing activity” when tested against live omicron virus. It also tested other monoclonals, including one from AstraZeneca that is used to prevent coronavirus infection, which had around a 30-fold reduction in neutralizing activity against omicron.
That monoclonal, Diamond said in an email, “is likely to be less effective but needs to be tested in vivo (animal models),” adding that it’s not known what a 30-fold reduction means, “but it cannot be good.” In contrast, he said, the Eli Lilly and Regeneron products “are likely to lose efficacy completely” (his emphasis) — and there now is some data in animals backing that idea.
Diamond pointed to an unpublished study posted to a preprint server on Jan. 24 that found in a mouse model, treatment with the Regeneron cocktail had no measurable virological effect against the omicron variant, despite being given at a higher dose than with previous variants.
While that experiment did not test Eli Lilly’s product, Diamond said that given the cell culture data, it’s “highly likely” the results would be the same.
“[W]hile we acknowledge in vivo studies are required, all data point to a major loss in efficacy of Lilly and Regeneron” antibodies, Diamond said, and “now data by another group … supports this point.”
Moreover, he said, waiting on clinical data isn’t practical in this situation. “I think there is no way to test in humans fast enough. I would prefer to give drugs (antibodies, small molecules) that do not show such loss in efficacy based on cell culture and animal data,” he said. “This is my reading of the FDA.”
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