As the omicron variant threatens to wipe out monoclonal antibodies, the U.S. is saving up one that will still work
With the omicron variant of the coronavirus poised to thwart most covid-19 treatments, U.S. public health officials are stockpiling the one monoclonal antibody that remains effective so that it can be deployed when the variant becomes more prevalent.
The decision to pause every-other-week shipments to states of the treatment, sotrovimab, shortly after Thanksgiving is part of a broader strategy to marshal the most effective tools to combat omicron, according to David Kessler, chief scientific officer of the White House covid-19 response team.
Omicron represents an estimated 3% of coronavirus cases in the United States, but in some states it is estimated to make up 13% of all cases, Rochelle Walensky, director of the Centers for Disease Control and Prevention, said Wednesday. Some hospitals are reporting even more concerning figures: At Houston Methodist, omicron grew from 13% of cases to more than 30% in four days. In New York, the percent of positive tests doubled in three days - a key sign of accelerating spread.
When omicron becomes dominant, it is expected to wipe out or weaken much of the covid-19 medicine cabinet, putting the focus on sotrovimab, which is an intravenous infusion from Vir Biotechnology and GlaxoSmithKline. Laboratory studies have shown that the treatment will hold up against the new variant. Antiviral pills that have yet to be authorized are also expected to help fill in the gaps.
Sotrovimab is an antibody that was identified in the blood of a patient who had recovered from the first severe acute respiratory syndrome virus, which emerged nearly two decades ago. It was chosen because it blocked SARS and SARS-CoV-2 and appeared to latch onto a region of the virus' spike protein that was less likely to change, according to George Scangos, chief executive of Vir. That made it more likely to stand up to future viral variants.
"I don't feel good that the competition got knocked out, frankly, because we're talking about lifesaving treatments," Scangos said. In the first year following the drug's authorization in May, Vir and GlaxoSmithKline had planned to manufacture 2 million treatments, but the companies are trying to find ways to increase manufacturing capacity.
The government moved to conserve sotrovimab when early analysis of omicron's mutations suggested the drug might hold up against the variant, Kessler said. A growing number of studies have bolstered confidence that it will still work. But the supply is limited, with about 50,000 total doses on hand - an inventory expected to grow to about 350,000 by early January, according to Kessler. The U.S. government distributed 180,000 doses to states before the pause in late November. The distribution data does not report which doses have been used.
As they took sotrovimab offline temporarily, officials increased shipments to states of monoclonals from Regeneron Pharmaceuticals and Eli Lilly. Those drugs are not expected to work against omicron but are highly effective against the delta variant - and are in greater supply. There were 400,000 doses of those treatments allocated to states for the period Nov. 29 to Dec. 26.
"The strategy of the U.S. government has been to ship those now, because delta is still the predominant strain," Scangos said. "Those antibodies are still going to be providing benefit to patients. Given that everybody expects omicron to take over, they are reserving sotrovimab for early next year. That makes complete sense."
Monoclonal antibody drugs are a central part of the treatment tool kit against covid-19, proving remarkably effective at keeping people out of the hospital. Three are authorized for treatment, and one was recently authorized for prevention in immune-compromised patients.
The treatments work by recognizing the hallmark spike proteins that stud the outside of the virus, and omicron's heavily mutated spikes are expected to dodge the Regeneron and Lilly drugs. Regeneron announced Thursday that its existing drug would have "diminished potency" against omicron and said it is working on a next-generation antibody cocktail that could begin human testing early next year.
Lilly spokeswoman Allison Howell said the mutations in omicron made it likely that the company's cocktail would lose some of its ability to block the virus, and Lilly is working to understand the threat. The company's scientists, she said, had always anticipated more monoclonals would be needed.
AstraZeneca announced Thursday that its long-acting monoclonal antibody, which was recently authorized as a treatment to prevent illness, was likely to retain protection against omicron. It is a cocktail, and a preprint study had suggested that omicron could escape the individual components of the cocktail.
"My concern is that if Omicron changes some more, as it's likely to do, then the new variant could completely evade the combination," David R. Martinez, a viral immunologist at the University of North Carolina Gillings School of Global Public Health said in an email.
Once omicron reaches a high enough level in certain regions, the government will switch to sotrovimab.
"The hard part is: tell me when you switch over," Kessler said.
Kessler said a team is working on details of when and how to make the switch. In areas dominated by delta, existing treatments from Regeneron and Lilly will continue to work well. But regions will reach a tipping point, and some areas may be close to that.
Roy M. Gulick, an infectious-diseases physician at Weill Cornell Medicine and co-chair of the National Institutes of Health's Covid-19 Treatment Guidelines panel, said the decision to switch will probably be made based on surveillance showing the prevalence of a variant in regions, not by waiting to see if an individual patient is infected with delta or omicron.
"Once it becomes the dominant variant, then most - but not all - of the monoclonal antibodies won't be effective against the infection anymore," Gulick said. "You will know, based on the public health approach, what's in your community."
In the spring and summer, the Eli Lilly monoclonal antibody cocktail, which did not work against the gamma and beta variants, was suspended in some states and regions, and eventually paused nationally. When the levels of those variants later dropped, it went back into use.
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