Gilead boasts of positive remdesivir data on mortality — but their analysis provokes the skeptics
Gilead is surging again off data that suggest its antiviral remdesivir might improve survival.
The new data come from an analysis Gilead conducted comparing the death rate and recovery time of patients in one of its remdesivir trials to a group of 800 patients “with similar baseline characteristics and disease severity” who received only standard-of-care around the same time. The result, they said, suggested that patients who received remdesivir had a 62% better chance at surviving than those who did not.
Retrospective looks are more suspect than placebo-controlled trials, so the data are far from conclusive. But it does add new evidence to the question of whether remdesivir can improve mortality. The NIH trial that led the FDA to authorize remdesivir for use in Covid-19 patients only showed that remdesivir could help patients recover faster. Fewer patients on remdesivir died in that trial than on standard-of-care — 8% vs 11% — but the results were not significant.
Former FDA chief scientist Luciana Borio said that data from observational studies are difficult to interpret, but that the bulk of evidence points to remdesivir helping patients survive Covid-19. “It is very likely that Remdesivir does indeed afford patients a mortality benefit,” she said in an email. “The gold standard RCT conducted by the NIH demonstrating the clinical benefit of Remdesivir in improving time to recover wasn’t powered to detect a difference in mortality. It doesn’t mean that there wasn’t one”
In a tweet, former FDA chief Scott Gottlieb called the results “encouraging” but urged that it needed to be confirmed. The company acknowledged in their press release that a prospective study was needed.
This is very encouraging but needs to be confirmed in a prospective trial. It appears to be a retrospective analysis of the phase III data using historical matched controls, suggesting a survival benefit in severe Covid patients. https://t.co/84dRMsInTA
— Scott Gottlieb, MD (@ScottGottliebMD) July 10, 2020
Gilead was up 2% pre-market on the news, from $74.71 to $76.18.
Other analysts and experts, though, were more skeptical and in some cases entirely dismissive. Peter Bach, the director for the center for health policy and outcomes at Memorial Sloan Kettering Cancer Center, said on Twitter that comparing trial participants to real-world patients only works when doctors have a good understanding of the disease, something that isn’t the case with Covid-19.
Getting ?’s on this. 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 both well understood. Not true in covid. https://t.co/J90gpXHZKA
— Peter B. Bach, MD (@peterbachmd) July 10, 2020
Baird analyst Brian Skorney compared the study to work from Didier Raoult, the French physician who published in February one of the first trials on hydroxychloroquine in Covid-19. That study, despite ginning up significant interest in the drug, was seen as rife with issues, including in “losing” 6 of the trial’s 26 patients “in follow-up,” 4 of whom died.
Who did this analysis? Didier Raoult? https://t.co/cmdzH5vg3R
— Brian Skorney (@BrianSkorney) July 10, 2020
In the study, 312 patients from Gilead’s open-label SIMPLE trial were compared to 818 real-world patients who had similar characteristics. Patients who received remdesivir had a 7.6% chance of dying, compared to 12.6% for those who received standard-of-care. That translates to 62% improved odds of survival — or slightly more than double the 30% improved odds the NIH trial’s raw numbers suggested.
SunTrust analyst Robyn Karnauskas said the survival rates in each trial were “comparable,” while acknowledging the study was “not an apples-to-apples comparison.”
The remdesivir patients in the analysis also had a 74.4% chance of recovering by day 14, versus 59.9% for standard-of-care.
Not every trial, though, has found remdesivir has a benefit. On the same day as the NIH readout, The Lancet published a study from China that found remdesivir improved neither mortality nor other patient metrics. That study, though, was ended early after the first outbreak in China ended.
For hospitals that can get their hands on it, remdesivir so far has been one of only two proven treatments for Covid-19, along with a generic steroid called dexamethasone. More antivirals and neutralizing antibodies, though, are now being studied, having become a growing focus of the Trump administration. If more therapies prove effective, the new Gilead data could help physicians choose the best option.
“While not as vigorous as a randomized controlled trial, this analysis importantly draws from a real-world setting and serves as an important adjunct to clinical trial data, adding to our collective understanding of this virus and reflecting the extraordinary pace of the ongoing pandemic,” investigator Susan Olender of Columbia University Irving Medical Center said in a statement.
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