Gilead’s RWD comparison for remdesivir is ‘not in the same league of evidence’ as controlled studies, says Bach
As real-world data continue to take on a more prominent role in clinical development, Gilead’s comparison of severe COVID-19 patients in a clinical trial of remdesivir versus a real-world cohort raises questions of how and when to it.
Gilead Sciences Inc. (NASDAQ:GILD) reported Friday that the mortality rate in its Phase III SIMPLE-Severe study of remdesivir was 7.6% vs. 12.5% in 818 patients from a RWD cohort receiving standard-of-care (SOC) treatment (odds ratio=0.38, 95% CI: 0.22, 0.68, p=0.001).
Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, reiterated to BioCentury his criticism of Gilead’s “choice to forgo a chance to produce substantive evidence about treatment effect.”
“This cross cohort comparison is not in the same league of evidence” as data from controlled trials, he said.
Gilead compared data from its Phase III SIMPLE-Severe study -- in which severe COVID-19 patients received SOC treatment plus a five- or 10-day course of remdesivir -- with RWD from patients treated with SOC alone. The company, which presented the results at a virtual international AIDS conference, said the two groups had similar baseline characteristics and disease severity but didn’t reveal specifics. The analysis was prespecified.
Industry stakeholders are eagerly looking for new sources and ways to use RWD to support the pandemic response (see “How Real-World Data are Poised to Break New Ground”).
According to Bach, it may be too early to apply RWD to clinical trials for COVID-19.
Shortly after Gilead announced the news, he tweeted that the “pandemic has taught us how wrong inferences can be when drawn from comparisons of unlike cohorts as here. The first principles test for these analyses is that natural history and its predictors [are] both well understood,” which is not the case for COVID-19.
SIMPLE-Severe’s exclusion of a control arm, plus the still evolving understanding of COVID-19’s progression, render Gilead’s association of the antiviral with a 62% reduction in death difficult to interpret.
Gilead acknowledged the survival benefit needs to be confirmed in a prospective clinical trial.
One prospective clinical trial -- the placebo-controlled ACTT study conducted by NIH -- has already failed to demonstrated a survival benefit for the drug.
ACTT, which randomized 1,059 hospitalized COVID-19 patients 1:1 to receive SOC plus placebo or SOC plus remdesivir, showed a trend toward a higher survival rate in the remdesivir group (see “Readout for Gilead’s Remdesivir”; “More Data Needed”).
In its statement, Gilead said the comparison of SIMPLE-Severe data with RWD add to the trend observed in ACTT.