Gilead releases another round of murky remdesivir results
Jason Mast
Associate Editor
EndPoints News
6/1/20
A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.
In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.
Baird’s Brian Skorney called the 10-day result “perplexing.” For him, the results confirmed what some public health experts have said since Anthony Fauci sat on an Oval Office couch at the end of April and announced the drug improved recovery time by 4 days and might improve mortality in their randomized trial: Remdesivir is a tool, but far, far short of a panacea.The data “continue to indicate a very marginal clinical benefit, while reinforcing that a benefit is likely more than random noise,” Skorney wrote. “We continue to believe that both the commercial opportunity for Gilead and the macro benefit of remdesivir to society, at large, is very limited.”
The market, which has been pouncing on every scrap of data for months, swiftly issued its verdict on the data, sending Gilead’s stock down 3% Monday morning.The latest trial is notable in part because unlike some of the earliest batches of data, patients in this trial were classified as “moderate” rather than “severe.” Virologists have said since early in the outbreak that the drug, which blocks an enzyme the virus relies on to replicate, will work better the earlier it is given, when viral load is high and before the virus has kicked the body into the inflammatory cycle that causes some of Covid-19’s worst effects. Although the NIH-run trial included both moderate and severe patients, the data published in The New England Journal of Medicine last month pointed to a faster recovery time for patients who entered the trial within 10 days after their symptoms start.
In this Phase III trial, 584 Covid-19 patients were randomized into three different arms: 5 days of remdesivir, 10 days of remdesivir, or a control arm consisting of standard of care. No placebo was given and the trial was open label.
Investigators found that on day 11, patients in the 5-day arm were 65% more likely to jump by at least 1 point on a 7-point “clinical score” scale that ranges from not hospitalized (1) to five different levels of oxygen and other treatment within a hospital (2-6) to death (7). In the 5-day arm, 76% of patients improved by 1 point or more and 70% improved by at least 2 points. In the standard-of-care arm, though, 66% still improved by at least 1 point and 61% of patients by at least 2 points.
Some investors were unimpressed by the difference, particularly given that the 10-day arm failed to reach significance.NIAID investigators, when laying out their Covid-19 trial in February, had initially sought to measure if remdesivir improves overall survival, but later changed their endpoint to encompass different clinical outcomes, including time-to-recovery. Although their trial pointed to 3-percentage-point improvement in mortality, that result was not statistically significant, and while remdesivir has become the drug of choice for doctors that can get their hands on it in the absence of any other proven therapy, its ability to help patients live longer remains unclear.
Gilead had originally designed the trial to measure the percentage of patients discharged by 14 days, but changed it to “enable assessment of clinical improvement at an earlier time point in patients with less severe disease,” the company told Endpoints News. In a note, Evercore ISI’s Umer Raffat said the discharge data was important to doctors and still lacking.
“While remdesivir ‘worked’ on a 7-point scale,” he said, “a fair amount of critical data has not been disclosed just yet.”
Jason Mast
Associate Editor
EndPoints News
6/1/20
A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.
In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.
Baird’s Brian Skorney called the 10-day result “perplexing.” For him, the results confirmed what some public health experts have said since Anthony Fauci sat on an Oval Office couch at the end of April and announced the drug improved recovery time by 4 days and might improve mortality in their randomized trial: Remdesivir is a tool, but far, far short of a panacea.The data “continue to indicate a very marginal clinical benefit, while reinforcing that a benefit is likely more than random noise,” Skorney wrote. “We continue to believe that both the commercial opportunity for Gilead and the macro benefit of remdesivir to society, at large, is very limited.”
The market, which has been pouncing on every scrap of data for months, swiftly issued its verdict on the data, sending Gilead’s stock down 3% Monday morning.The latest trial is notable in part because unlike some of the earliest batches of data, patients in this trial were classified as “moderate” rather than “severe.” Virologists have said since early in the outbreak that the drug, which blocks an enzyme the virus relies on to replicate, will work better the earlier it is given, when viral load is high and before the virus has kicked the body into the inflammatory cycle that causes some of Covid-19’s worst effects. Although the NIH-run trial included both moderate and severe patients, the data published in The New England Journal of Medicine last month pointed to a faster recovery time for patients who entered the trial within 10 days after their symptoms start.
In this Phase III trial, 584 Covid-19 patients were randomized into three different arms: 5 days of remdesivir, 10 days of remdesivir, or a control arm consisting of standard of care. No placebo was given and the trial was open label.
Investigators found that on day 11, patients in the 5-day arm were 65% more likely to jump by at least 1 point on a 7-point “clinical score” scale that ranges from not hospitalized (1) to five different levels of oxygen and other treatment within a hospital (2-6) to death (7). In the 5-day arm, 76% of patients improved by 1 point or more and 70% improved by at least 2 points. In the standard-of-care arm, though, 66% still improved by at least 1 point and 61% of patients by at least 2 points.
Some investors were unimpressed by the difference, particularly given that the 10-day arm failed to reach significance.NIAID investigators, when laying out their Covid-19 trial in February, had initially sought to measure if remdesivir improves overall survival, but later changed their endpoint to encompass different clinical outcomes, including time-to-recovery. Although their trial pointed to 3-percentage-point improvement in mortality, that result was not statistically significant, and while remdesivir has become the drug of choice for doctors that can get their hands on it in the absence of any other proven therapy, its ability to help patients live longer remains unclear.
Gilead had originally designed the trial to measure the percentage of patients discharged by 14 days, but changed it to “enable assessment of clinical improvement at an earlier time point in patients with less severe disease,” the company told Endpoints News. In a note, Evercore ISI’s Umer Raffat said the discharge data was important to doctors and still lacking.
“While remdesivir ‘worked’ on a 7-point scale,” he said, “a fair amount of critical data has not been disclosed just yet.”
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