With daily coronavirus case counts and hospitalizations soaring, the debut of two medicines that can help keep high-risk COVID-19 patients out of the hospital would seem to be a breakthrough.
Eli Lilly’s monoclonal antibody treatment was authorized for emergency use earlier this month. Regeneron’s version — a mix of two antibodies that President Donald Trump received after his diagnosis in October — was authorized on Saturday.
But like so many treatments tried during the pandemic, monoclonal antibodies are not magic bullets. They pose logistical, medical, and ethical challenges that could reduce their availability — and patients’ demand for them. In fact, Temple University Hospital has drawn no participants for a trial of Lilly’s therapy, while Jefferson University Hospital has had fewer than 10.
Here is a deeper look at those challenges.
Monoclonal antibodies are laboratory-made proteins that mimic the natural antibodies produced by the body to fight the coronavirus as it launches an infection.
These antibody treatments are for newly diagnosed people who have mild to moderate COVID-19 symptoms, but an elevated risk of worsening and needing hospitalization. Patients who are over age 65, or obese, or have chronic health problems — or all of the above — are eligible under the U.S. Food and Drug Administration’s authorization.
The thing is, there is no sure way to predict who will need hospital care, and even high-risk people are very unlikely to get that sick. That is clear from the ongoing clinical trials conducted at sites across the country.
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In Regeneron’s trial, 3% of patients on the antibodies were hospitalized or went to the emergency room, compared to 9% of patients on a placebo. In the Lilly study, 1.6% on the drug were hospitalized vs. 6.3% on placebo.
These preliminary results were based on relatively small numbers of patients: 452 in Lilly’s study and 799 in Regeneron’s.
“The vast majority of people are going to recover on their own,” said Katherine Belden, an infectious disease specialist overseeing Jefferson University Hospital’s participation in the Lilly trial. “With this intervention, can you shut down viral replication early enough that they don’t progress? It’s a promising therapy, but I want to emphasize the study is ongoing.”
The current evidence is so scant that the Infectious Diseases Society of America has recommended against routine use of the therapies unless the patient understands and accepts the uncertainties.
“I think monoclonal antibodies show the potential for benefit,” Rajesh Gandhi, an infectious disease specialist at Massachusetts General Hospital, said during a society video briefing on Monday. “But it’s very difficult with such small numbers to be certain as to how big of an effect and … which patients are most likely to benefit.”
As for risks, the FDA warns that life-threatening immune system overreactions are possible, and that antibody therapy can actually make outcomes worse for patients who are already hospitalized or need supplemental oxygen.
“We really do need to identify patients early for them to see a benefit,” Belden said.
In the Lilly trial, patients were treated within 72 hours of a positive coronavirus test. In the real world, high-risk patients may not consult their doctors that quickly, especially since up until now, people with mild to moderate symptoms have been advised to stay home and quarantine.
Getting antibody treatments is not as easy as swallowing pills. The drugs must be given intravenously in a hospital or infusion center.
That’s tricky because contagious COVID-19 patients are a danger to other patients, particularly immune-compromised patients getting intravenous chemotherapy.
“We don’t want people running to the emergency room to get this therapy. We don’t want people running to infusion centers, where there are patients with cancer,” University of Pittsburgh physician Walid Gellad told NPR. “And we don’t want them running to their primary care doctor’s offices that are not set up for these infusions. It is not clear at all where the infusions are going to happen.”
The hour-long infusion, and the rather small chance of benefit, has made recruiting patients for the trials challenging. Temple University Hospital, one of 41 sites testing Eli Lilly’s antibody therapy, has not yet enrolled any patients, a spokesperson said. At Jefferson, enrollment is in the “single digits,” Belden said.
Regeneron, meanwhile, aimed to have 2,100 patients by the estimated completion date of Dec. 19, according to its protocol on clinicaltrials.gov. The data submitted to the FDA late last month were based on 799 patients.
The recruitment challenges could get worse now that patients can seek the antibody therapy outside a trial — and thereby ensure they aren’t getting a placebo.
“That’s something we’re discussing right now,” Belden said. “It’s going to depend on the supply. There may be patients eligible for the trial who are not eligible under the emergency use authorization.”
While demand for the drug from patients who meet the eligibility criteria remains to be seen, initial supplies will be limited. The U.S. Department of Health and Human Services is overseeing the purchase, and will dole out vials each week to each state based on needs.
New Jersey’s first batch of 1,550 vials of Lilly’s therapy “has been allocated to all hospitals,” state Department of Health spokesperson Nancy Kearney emailed last week. “We expect to be allotted additional units weekly based on hospital census and other factors.”
Pennsylvania’s first 2,300 vials were also distributed to health systems last week, health officials said.
A big concern is equitable access to the antibody therapies. Although the government is paying for the drugs, patients may face charges or co-pays for the infusion procedure. That could be a barrier for patients in low-income communities, which have been disproportionately hurt by the pandemic. Finding a physician or health clinic able to make a referral for the therapy in a timely fashion could be another obstacle.
The University of Pittsburgh Medical Center is trying to lower the barriers with a selection system that gives an edge to high-risk COVID-19 patients who are essential workers or live in poor neighborhoods, according to STAT, the health news website.