New Gilead remdesivir COVID-19 data show up old problems with limited data

Gilead Sciences has posted data on 53 severe COVID-19 patients who received remdesivir on a compassionate use basis. More than two-thirds of the patients improved after receiving remdesivir, although the lack of a control arm makes it hard to tell what role the antiviral played in their recoveries.

Remdesivir, a nucleotide analogue prodrug originally tested in Ebola patients, has emerged as one of the top near-term hopes of improving outcomes in COVID-19 patients. Responding to the dire need, Gilead has made remdesivir available to more than 1,700 people on a compassionate use basis while also providing it to subjects in its own clinical trials and those run by other sponsors.

Gilead provided a snapshot of the experiences of patients treated on a compassionate use basis in a paper published in The New England Journal of Medicine. The study covered 61 patients, eight of whom were excluded due to a lack of post-treatment data or a dosing error.

That left Gilead with an analyzable cohort of 53 patients, 30 of whom were on mechanical ventilation at the start of the study. The patients received 10 days of treatment with remdesivir and were then tracked for a median of 18 days.

As of the end of the follow-up period, 68% had an improvement in oxygen-class support. More than half of the mechanically ventilated patients were extubated. Almost half of the patients in the study were discharged in the analyzed period. Seven patients died. All bar one of the people who died were receiving invasive ventilation at baseline.

The lack of a control arm makes it hard to interpret the data. It is possible to compare the death rate to that seen in a clinical trial of Abbott’s Kaletra, 22%, to make the case that remdesivir is doing some good. But such cross-trial comparisons are rendered unreliable by confounding variables, such as the characteristics of the patients enrolled.

Given the remdesivir study lacked a control arm, few hard conclusions can be drawn from the data. One clear positive is the lack of safety red flags, although that was arguably to be expected based on how remdesivir performed in a larger study of Ebola patients.  

The strongest statement Jefferies analysts made in response to the data was that the results “suggest remdesivir may work and is generally safe.” As the Jefferies analysts note, the availability of viral load data would instill more confidence that the improvements seen in the study were linked to the drug. Yet the NEJM paper lacks those data, rendering it unclear whether remdesivir is squashing the coronavirus.

As such, the NEJM paper changes little. The focus is still on results from randomized clinical trials of remdesivir in moderate and severe patients that Chinese sponsors initiated as the virus began to take over Wuhan. In an update posted late last week, Gilead CEO Daniel O’Day said he expects to receive preliminary data from the study in severe patients at the end of the month. That study stopped early due to “stalled enrollment,” O’Day said. 

Expectations for the data in severe patients are modest, with the Jefferies analysts saying benefits in the 30% to 40% range are unlikely. That makes the May data on patients with moderate symptoms, a population that may be more responsive to remdesivir, perhaps the key determinants for the fate of the drug. Gilead has told investors not to base the company's future around the drug, but shares in the Big Biotech still jumped nearly 3% Monday morning.