ViewPoints: Any data is good data for remdesivir

Despite some obvious shortcomings from the data set, the first look at outcomes from COVID-19 patients treated with remdesivir has inspired some optimism, while raising expectations for the 'real' data later this month.

What happened

Gilead Sciences released results from its analysis of compassionate use of remdesivir in patients with COVID-19, reporting a mortality rate of 13% among 53 treated patients. The compassionate use cohort did not include a control group, but the company noted that compared to some regions- specifically, a 22% mortality rate from a cohort treated with lopinavir in Wuhan, China- the treatment offered promising results.

The company highlighted the apparent utility for remdesivir in severe patients already receiving ventilator support; 68% experienced an improvement in oxygen support at 18 days, including 57% of patients on ventilators. Mortality among patients on ventilators was 18%.

Four patients were receiving extracorporeal membrane oxygenation (ECMO), reflecting the most severe oxygen support status. Three improved sufficiently to stop receiving it.

The company said there were no new safety events in the cohort, reporting 12 patients with severe adverse events that were generally more severe in patients with invasive ventilation.

What it means

There are plenty of caveats to consider in the data set, which could otherwise bode well for the prospects of Gilead's upcoming clinical trial data. The authors highlighted the shortcomings themselves, writing that "interpretation of the results of this study is limited by the small size of the cohort, the relatively short duration of follow-up, potential missing data owing to the nature of the programme, the lack of information on eight of the patients initially treated, and the lack of a randomised control group."

Further, the analysis did not collect any data on viral load, which could have helped to validate the contribution of remdesivir's antiviral activity in improving patients. And while the company has floated the idea of five and 10 day treatment courses- with five days being the favourable option for an IV-delivered therapy- the study authors noted that inconsistency in treatment duration limited their ability to assess differences between regimens.

The biggest hurdle to drawing conclusions from the data is the lack of randomisation or a control group, which is complicated by variability in patient outcomes and hospital standards from region to region and over time. While the analysis argues that there's a favourable comparison between a 13% mortality rate for remdesivir and the 22% reported in Wuhan, it's not clear how standard of care might have differed region to region as patient management was optimised as the pandemic progressed.

However, Gilead points to higher ventilation rates in its compassionate use cohort to suggest that it achieved a lower mortality rate even in the face of a more severe patient population.

The analysis was also missing some key features that analysts had been expecting- namely, an indication of whether efficacy was tied to treatment early in disease progression. Evercore ISI's Umer Raffat noted that "the paper suggests timing of remdesivir initiation did NOT correlate with efficacy"- which would be contrary to prior predictions if validated in clinical trials.

Next steps

Gilead acknowledged the shortcomings of the analysis; in an open letter, CEO Dan O'Day wrote that "we recognise the limitations of these compassionate use data from a purely investigational perspective, while knowing they are of the greatest significance for the patients whose symptoms improved."

O'Day estimated that a more satisfying data set- this from a US trial of remdesivir in moderate to severe patients- will be available at the end of April. Meanwhile, China-based studies that had fired up in February have since fizzled out, as successful management of the pandemic has slowed patient enrolment. A publication from the halted trial is expected "when available." In May, data will become available from a National Institute of Allergy and Infectious Disease (NIAID)-sponsored trial, on top of Gilead's second US-based study in patients with moderate symptoms.

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