The federal government has resumed shipping all three monoclonal antibody treatments—including one made by Indianapolis-based Eli Lilly and Co.—that are authorized for early-stage COVID-19 to states despite evidence that two might be ineffective against the omicron variant of the coronavirus that is sweeping the country.
The move has drawn mixed reactions from physicians and experts. Some are concerned many of the costly infusions will be useless, causing confusion among patients who have heard glowing reports about the treatments. They note that it can be difficult for doctors to determine whether their patients are infected with omicron or the previously dominant delta variant, making treatment decisions tricky.
But other physicians remain eager to receive even less-effective treatments because of a severe shortage of sotrovimab, the monoclonal antibody therapy that, according to laboratory tests, works best against omicron. Sotrovimab was developed by British pharmaceutical giant GlaxoSmithKline PLC with U.S.-based Vir Biotechnology.
Many doctors say they would rather have access to some monoclonal antibodies than none, partly because some of their patients might be infected by the delta variant.
That raises difficult questions. “Is it ethical and practical to give those treatments to people who you think almost certainly have omicron?” said Jeanne Marrazzo, director of infectious diseases at the University of Alabama at Birmingham. “Most patients are demanding something.”
She said the current situation is “a transition period,” as omicron overtakes delta. “But it is very murky, very confusing to patients.”
David Kessler, the chief scientific officer for the administration’s COVID response, said the government has been responding to requests from state and local health officials in making all three monoclonal antibodies available. But the administration has made clear that the two that don’t work against the omicron variant should be used “only if the delta variant represents a significant proportion of infections in the region and then only with the explicit understanding that these treatments would be ineffective if the patients are infected with the omicron variant.”
The bottom line, he said, is “don’t use [those treatments] unless you have the testing that shows that a patient does not have omicron.” He added that the administration this week will re-evaluate whether it should continue making all three antibody treatments available considering omicron’s overwhelming dominance.
After the omicron variant emerged around Thanksgiving, the Department of Health and Human Services briefly halted shipments of sotrovimab to stockpile it for the time when omicron became more prevalent. Shipments resumed weeks after that, as omicron became increasingly rampant.
On Dec. 23, the department announced it would pause shipments of two other monoclonal antibody treatments, made by Regeneron Pharmaceuticals and Eli Lilly, which laboratory tests have shown are less effective against the new variant.
Last week, the administration resumed shipments of those two medications. The latest reversal followed complaints from Florida Republican Gov. Ron DeSantis and some doctors that the Regeneron treatments could help in places where the delta variant of the virus is still infecting people. DeSantis also said he was not convinced the Regeneron and Lilly cocktails were ineffective against the omicron variant.
Those two treatments were used heavily last year to prevent hospitalizations of people infected by the delta variant, but have proven less effective against omicron in lab tests. (An injectable monoclonal antibody, AstraZeneca’s Evusheld, was approved last month for pre-exposure use in immunocompromised people; the company said lab studies show it “retained neutralizing activity” against omicron.)
New antiviral pills also are expected to be effective against both the delta and omicron variants, but those won’t be widely available for weeks or even months.
The Regeneron and Lilly medications, given to outpatients by infusion or injection, are free and have caused few side effects. They are authorized for anyone with mild to moderate disease who doesn’t need supplemental oxygen. They also can be given prophylactically to high-risk patients, including people 65 and older, who have been exposed to the virus.
The Biden administration agreed Dec. 31 to start shipping the Regeneron and Lilly products last week. In a news release Tuesday, DeSantis, one of the most vocal proponents of monoclonal antibody treatments, took credit for forcing the administration to change course. He said the state would soon receive an additional 30,000 doses of monoclonal antibodies.
In an email, DeSantis’s spokeswoman, Christina Pushaw, asserted that “there have been Omicron cases treated with other [monoclonal antibodies] that showed significant improvement, contrary to the initial study that came out and apparently informed the now-reversed HHS policy.”
A spokeswoman for HHS’s assistant secretary of preparedness and response, who is in charge of distributing the monoclonal antibodies, referred a reporter to updates on the agency’s website that announced the change of strategy.
The latest update attributed the change of heart to a recommendation from a panel at the National Institutes of Health, which concluded that “if the Delta [variant of concern] still represents a significant proportion of infections in the region and other options are not available or are contraindicated, patients can be offered” the other two monoclonal antibody treatments.
But experts worry that patients and doctors will be flummoxed by the advice they must digest about different monoclonal antibody treatments. In the vast majority of cases, they noted, physicians making treatment decisions do not know whether their patient is infected by the omicron or delta variants, because little genomic sequencing is being done. Even when tests are sequenced, the results are usually too late to be considered in treatment deliberations.
If omicron now accounts for 95% of all new U.S. cases, as Centers for Disease Control and Prevention Director Rochelle Walensky said Wednesday, the newly reauthorized therapies will have little effect.
“When delta and omicron were 50-50, fighting it out, I was very enthusiastic about continuing to use the Regeneron and Lilly monoclonals as long as there was a way of differentiating between the two,” said John W. Mellors, chief of infectious diseases at UPMC School of Medicine in Pittsburgh. “The dilemma was there wasn’t a rapid FDA-approved test to differentiate omicron from delta. And the reality is sequencing takes several days.”
Now, he said, “if I had local data that was reliable, that was broad enough that suggested delta is still prominent, yes I might give the antibody. But I’d want real time data on what people are becoming infected with.”
Most hospitals do not have the capability to do real-time sequencing to determine how to treat individual patients, Marrazzo said. She said her medical center’s laboratory regularly sequences batches of patient samples to determine the prevalence of each variant.
Marrazzo said the last time her hospital lab performed sequencing to determine the prevalence of the variants, on Dec. 22, the results showed almost 60% of new cases were caused by omicron and the rest by delta. But now, state data is showing that omicron is responsible for 99.8% of new cases in Alabama.
Marrazzo said the medical center on Tuesday received its first shipment of sotrovimab—16 courses that already are gone. She said physicians were using the Regeneron and Lilly treatments as backup, but now will halt those because of the overwhelming dominance of omicron. She expects more sotrovimab next week.
Nicole Iovine, an infectious-disease physician and chief epidemiologist for University of Florida Health in Gainesville, said in some areas of the country, especially parts of the west and Midwest, the delta variant still accounts for a portion of COVID-19 infections.
“In certain parts of the country, Regeneron is still likely to have an effect,” she said.
A CDC map of omicron’s spread shows it accounts for at least 77.4% of sequenced infections in each of 10 regions, with most at greater than 90%.