In September, as doctors prepared for a fall and winter COVID-19 surge across the U.S., they sounded alarms about inadequate supplies of the antiviral medication remdesivir to treat their patients. But that supply concern seems to have been addressed: Gilead, remdesivir’s U.S. manufacturer, confirmed that they are “meeting real-time, global demand” in an email to Medical Bag.

“We were originally very concerned there would be a shortage of remdesivir, but that has not happened,” says Otto Yang, professor of medicine in the division of infectious disease at the David Geffen School of Medicine at UCLA. There currently seems to be an adequate supply, even during the current surge in cases and hospitalizations, he says.

The 4-, 10-, and 20-milligram doses of dexamethasone, a corticosteroid also approved as a COVID-19 treatment, on the other hand, are currently listed as “sporadic availability expected” on the U.S. Food and Drug Administration website. But because dexamethasone is one of many steroids that are “pretty much interchangeable,” there’s little concern of a shortage, Yang says.

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Margaret Green, an infectious disease doctor at the University of Washington in Seattle, said that supply of both remdesivir and dexamethasone was stable at her hospital as well. That is aided in part by the fact that UW Medicine has been careful about prescribing remdesivir since it was first cleared under the Emergency Use Authorization. “Our system set up an allocation team so all requests for remdesivir were adjudicated based on their evidence of likelihood of benefit. I think that trained all of us providers to think about what the evidence was for who this would help with and use it judiciously. And we have not had any supply shortages.”

At UW Medicine, the likelihood of benefit is a blinded process based on the report from the ACTT-1 randomized clinical trial, whose results were published in The New England Journal of Medicine. “We’re … giving it [to] patients who are hypoxic and needing supplemental oxygen,” Green says. Standard treatment is a five-day course of remdesivir, based on another randomized study of moderate-severity, hospitalized COVID-19 patients published in The Journal of the American Medical Association that showed no benefit for a longer, 10-day course.

Remdesivir was in the headlines again November 18, as the World Health Organization (WHO) recommended against using the treatment in hospitalized patients of any severity based on the WHO Solidarity Trial, which concluded that remdesivir provided no benefit. But Yang called the trial “highly flawed.”

“In a nutshell, it wasn’t placebo-controlled,” he says. “It was not quality controlled in terms of how the data were reported; it only followed patients for a certain amount of time and excluded patients that didn’t get followed for that amount of time. So, in fact, if a patient got better quickly and left the hospital early, they would be lost to the follow-up,” he says. This was in addition to the study being conducted in “resource-limited settings” where ICU and overall care may not have been adequate. If remdesivir works, it’s still only a small effect compared with how the patient is cared for overall, he explains. “If the patient doesn’t have a ventilator available, it doesn’t matter if they have remdesivir or not.”

Remdesivir and dexamethasone are “definitely not silver bullets,” Yang says. Remdesivir does seem to shorten recovery time for patients by days, with a median of 12 days in hospital versus 17 for the placebo group, and may reduce mortality by a small margin. Dexamethasone appears to reduce mortality in ventilated patients by a third, and one-fifth in patients only requiring oxygen, according to preliminary reports from the WHO.

Better therapeutics are sorely needed. Yang is concerned that patients are hesitating to sign up for placebo-controlled studies because they fear not receiving an active ingredient. “That’s going to slow down development of new agents if people don’t participate,” he says. “Without the placebo group, we don’t have a way to figure out if the drug works or not.”

He also said that UCLA had received “some” doses of Eli Lilly’s monoclonal antibody treatment, which received emergency use authorization on November 9. He suspects there may be issues with how that treatment is allocated, though that remains to be seen. Distribution for the COVID-19 vaccines could also be a hurdle when the first million or so doses are available.

While therapeutic supplies are stable, Green is concerned about rising cases — hospitals across the country are overwhelmed amid the latest surge, according to AP News — and public health messaging that doesn’t seem to be landing. She’s hopeful that vaccines on the horizon will enable healthcare workers to continue doing their jobs. At the moment, however, “everyone is exhausted,” she says. “We’re all trying our best. But right now our best isn’t good enough.”

Update: Since reporting this story, the WHO released the full Solidarity Trial report. “The findings for mortality and for initiation of ventilation cannot have been appreciably biased by the open-label design without placebos, or by variation in local care or patient characteristics, and were little affected when homogeneity was increased by stratification according to geographic region, age, or use of ventilation at entry. No trial drug reduced the initiation of mechanical ventilation,” the report says. It further argues that the reduction in patient hospital stays as measured by the ACTT-1 study could be accounted for because the group receiving remdesivir had fewer severe cases (patients needing oxygen or ventilation) by chance. “This chance imbalance might account for some of the differences in time to recovery between ACTT-1 and the Solidarity trial,” according to the report.