Some clinicians are confused about the best dosing for Eli Lilly’s new Covid-19 treatment, which the Food and Drug Administration approved for emergency use on Monday.
The drug is a monoclonal antibody, a lab-concocted version of what our bodies produce to fight off the new coronavirus. The FDA gave doctors the green light to give bamlanivimab to those 12 or over whose Covid-19 is not yet serious enough to require hospitalization, but who are at high risk of getting to that point.
Reducing the number of people who get sick enough to require admission would be a huge boon, as it could help keep medical centers from being overwhelmed. Preliminary findings showed that the medication could potentially have that effect if given early enough.
Some clinicians wondered, though, if the decision to authorize doses of 700 milligrams — rather than a greater quantity — was made in part because the drug is in short supply.
In data first released in September, researchers tried three different doses, but only the middle one — 2,800 milligrams — met the primary goal that the study had set, of reducing the amount of virus found inside patients. Given that that wasn’t the case for those patients who got either 700 milligrams or 7,000 milligrams, it seemed like this finding might just be a fluke. After all most patients, even those who’d gotten a placebo, had almost no virus in them at all after 11 days, anyway.
“What we understand with Covid is that the viral load is highest at the very beginning and it goes down by seven or eight days,” explained Helen Boucher, chief of geographic medicine and infectious diseases at Tufts Medical Center, in Boston, who wasn’t involved in the research. “By day 11 almost everybody’s viral load was better: We can’t make too much out of that. There’s no biologic plausibility as to why you’d see this only in the middle dose and not the lower or higher dose.”
But that left people wondering whether the FDA had authorized the best possible dose.
“This is not an ideal situation, because the dose discrepancies have confused people,” wrote Walid Gellad, director of the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing, in an email to STAT. “Also the government already purchased 700mg vials, which may be relevant here, and a 2800mg dose would mean many fewer doses.”
An Eli Lilly spokesperson said the company is “confident in the growing body of evidence” supporting a 700 mg dose and that the more meaningful findings were that 10% of those who got the placebo ended up in the hospital or at the emergency room, while only 3% of those who got the drug did.
In a Tuesday press conference, Janet Woodcock, the leader of therapeutics for Operation Warp Speed — the federal government initiative to spur the development of Covid-19 drugs and vaccines — acknowledged that only the 2,800 milligrams met that particular goal, but said that that didn’t undermine the efficacy of the 700-milligram dose. “If you look at the hospitalizations … there was a decrease in each of the subgroups,” she said. She directed questions about this to the FDA, but said, “the lower dose is a rational choice in this situation. You don’t want to give more of a drug than you need. … I think you could probably go lower, frankly.”
The Department of Health and Human Services is planning to begin distribution of vials this week, using weekly numbers of Covid-19 cases and hospitalizations to determine how much of the supply should go where. Each state and territorial health department will then allocate its portion to treatment centers.
Officials anticipate logistical challenges, because the drug has to be administered through an hourlong infusion, and is authorized only for coronavirus-infected outpatients.
Given the limited quantity of the drug available, there are also thorny ethical questions at hand. To be eligible, for instance, you have to be at high risk for developing severe Covid-19. “That includes a lot of people who are traditionally underserved by the health care system,” said Boucher. “The challenge before me as a clinician is: How to use it equitably if it’s in such low supply?”
As for the questions about dose, she hopes those will be answered as studies continue and more data are released. “We don’t have all the data that FDA has,” she said. For now, she warned, of the results that have been published so far, “The key is the numbers are pretty small, and that can’t be emphasized enough.”