Since the National Institutes of Health released preliminary findings backing an FDA emergency authorization of Gilead Sciences’ COVID-19 therapy remdesivir, the medical community has been calling for detailed results to guide treatment practice. And now the data are here.
As the National Institute of Allergy and Infectious Diseases (NIAID) previously outlined, treatment with remdesivir cut recovery time for hospitalized patients by about 30%. Updated two-week death rates leaned further in the Gilead drug's favor at 7.1% versus 11.9% for placebo, though the difference wasn’t statistically significant, according to The New England Journal of Medicine. Previously, the death rates were 8% and 11.6%, respectively.
In a Saturday note to clients, SVB Leerink analyst Geoffrey Porges argued the numeric improvement in mortality, if further validated, “can change sentiment” about COVID-19, and that getting patients to recover faster can alleviate pressure on hospital systems in response to increases in cases.
The 1,063-patient study showed remdesivir’s benefits appear greatest for hospitalized patients in the middle of the disease-severity spectrum. For those who required oxygen supplementation but were not mechanically ventilated, remdesivir cut the time to recovery by 47% compared with placebo.
But remdesivir didn’t much help patients with mild or moderate disease, and outcomes for patients on invasive ventilation or extracorporeal membrane oxygenation were nearly the same in both arms of the study.
Overall, the probability of improvement in clinical status was 50% higher among remdesivir patients than in placebo patients.
“It is likely that the treatment benefit from remdesivir will increase in the real world once the lessons of this trial and other studies are incorporated into routine treatment practices,” Porges said.
Still, as Evercore ISI analyst Umer Raffat sees it, the NEJM paper is missing one key data set. “The single most important data disclosure that I was awaiting was this: How does mortality look different in patients that take remdesivir early?” he said. “These early trials on COVID are all about identifying not only whether a drug works, but also when to initiate the drug.”
The new study does separate recovery data for patients randomized within 10 days of symptom onset and those randomized after that point. But it doesn’t specify disease severity in either of those two groups.
Besides, the study, dubbed ACTT-1, stopped early at the recommendation of an independent data monitoring panel. Therefore, only a proportion of patients had completed the trial through day 29, the primary endpoint evaluation date, leaving 132 patients in the remdesivir group and 169 in the placebo group unanalyzed.
Porges acknowledged that, while large, ACTT-1 is just one study. Previously, in a Chinese study that didn’t complete due to low enrollment, researchers only found a numerically faster clinical improvement with remdesivir use compared with placebo in patients who started treatment with symptom duration of 10 days or less.
Gilead itself is running two studies in moderate and severe patients, respectively. In a Friday statement, the company said the moderate-patient trial is expected to read out at the end of this month. Meanwhile, the NIAID has started enrolling patients in the ACTT-2 trial combining remdesivir, an antiviral, with Eli Lilly’s anti-inflammatory JAK inhibitor Olumiant.
Physicians have been waiting anxiously for the detailed results to help direct already limited supply of the drug to those most likely to benefit. Gilead has committed to donating 1.5 million doses of the drug by June, which, depending on the duration of treatment, could cover 150,000 to 250,000 treatment courses. As the only drug to have shown a clear benefit in a large, well-designed clinical trial so far, remdesivir demand is outstripping supply.
After that initial supply runs out, Gilead will pivot to a commercial plan, and all eyes will be on how the biotech plans to charge for the drug. Based on the preliminary ACTT-1 results, drug cost watchdogs at the Institute for Clinical and Economic Review previously pegged $4,460 per course as a fair price for remdesivir.