Early data from the Phase III ACTT trial led by the US National Institute of Allergy and Infectious Diseases (NIAID) indicate that hospitalised patients with advanced COVID-19 given Gilead Sciences' remdesivir had a 31% faster time to recovery than those on placebo. NIAID director Anthony Fauci, a key member of the White House coronavirus task force, said "although a 31% improvement doesn't seem like a knockout 100%, it is a very important proof-of-concept because what it has proven is that a drug can block this virus…this is very optimistic," and he suggested remdesivir "will be the standard of care."
The study, launched in late February, has an estimated enrollment of 1063 hospitalised adult patients diagnosed with COVID-19, with participants randomised to receive intravenous remdesivir for up to a 10-day total course, or placebo. The primary outcome measure is time to recovery by day 29, with recovery defined as being well enough for hospital discharge or returning to normal activity level. A key secondary goal of the study will look at treatment-related improvements on an eight-point scale at the 15-day mark.
Specifically, preliminary results showed the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those in the placebo group. Results also suggested a survival benefit, with a mortality rate of 8% for remdesivir-treated patients versus 11.6% for placebo, although Fauci noted the mortality benefit of the drug "has not yet reached statistical significance." The NIAID said detailed information about the trial results, including more comprehensive data, will be available in a future report, and that it will also give an update on plans for the ACTT trial moving forward.
Commenting on the news, RBC Capital Markets analyst Brian Abrahams said "the bottom line here is it is increasingly likely that this is an active drug with some benefits." However, he noted that "the magnitude is not overly dramatic, but it will probably be made available more broadly and become one of several potential future tools in physicians' arsenal." A report in The New York Times citing a senior official in the Trump administration said the FDA is moving to fast-track remdesivir as an emergency treatment for the novel coronavirus, with a decision potentially announced as early as Wednesday.
Meanwhile, Gilead also reported top-line results from the late-stage SIMPLE study that the company is conducting, with data showing that a five-day dosing duration of remdesivir led to "similar improvement in clinical status" as the 10-day treatment course being evaluated in the NIAID study and other ongoing trials. The initial phase of the SIMPLE trial, which is not placebo-controlled, randomised 397 hospitalised patients with severe manifestations of COVID-19 disease to receive intravenous remdesivir until either day five or 10, on top of standard care. Gilead noted that an expansion phase of the study was recently added and will enroll an additional 5600 patients, including patients on mechanical ventilation.
In results disclosed Wednesday, Gilead said the time to clinical improvement for 50% of patients was 10 days in the five-day treatment group, and 11 days in the 10-day group. Clinical improvement was defined as an improvement of two or more points from baseline on a seven-point scale, ranging from hospital discharge to increasing levels of oxygen support to death. Patients were deemed to have achieved clinical recovery if they no longer required oxygen support and medical care, or were discharged from the hospital.
Gilead noted that more than half of patients in both treatment groups were discharged from the hospital by day 14, with 60% of those in the five-day group and 52.3% of those in the 10-day group. It added that in that time frame, 64.5% of patients in the five-day treatment group and 53.8% of those in the 10-day group achieved clinical recovery.
Meanwhile, an exploratory analysis indicated that patients who received remdesivir within 10 days of symptom onset had improved outcomes compared with those treated after more than 10 days of symptoms. Pooling data across treatment arms, Gilead said that by the 14-day mark, 62% of patients treated early were able to be discharged from hospital, compared with 49% of those who were treated late.
In terms of safety, the drugmaker said remdesivir was generally well-tolerated in both the five- and 10-day treatment groups. The most common adverse events in either group were nausea, as well as acute respiratory failure, which occurred at rates of 6% and 10.7% in the five- and 10-day groups, respectively. Grade 3 or higher ALT liver enzyme increases occurred in 7.3% of patients overall, with 3% discontinuing remdesivir due to elevated liver tests.
Merdad Parsey, chief medical officer at the company, said these findings complement data from the NIAID-led trial. The five-day regimen "could significantly expand the number of patients who could be treated with our current supply of remdesivir," he remarked, adding "this is particularly important in the setting of a pandemic." Gilead expects data at the end of May from the second SIMPLE study evaluating the five- and 10-day dosing durations of remdesivir in patients with moderate COVID-19 disease.
Jefferies healthcare strategist Jared Holz suggested remdesivir will likely be approved for use in certain settings, at least until better alternatives are available. "There is a massive bias to look at the data with half-glass-full approach," he said, but that is "totally fair given the current predicament."
Last week, the World Health Organization accidently published negative results of another remdesivir trial in China, showing that the antiviral did not help hospitalised adult patients with severe COVID-19 avoid death or reduce their viral load. Commenting at the time, Gilead said the draft document mistakenly released by the WHO, and pulled from the agency's website soon after, contained "inappropriate characterisations" about the study, and that there could still be potential benefits for patients who are treated early on (for related analysis, see ViewPoints: Gilead takes issue with remdesivir’s ‘flop’ in Chinese Phase III trial). The authors of that study, which was published in The Lancet on Wednesday, confirmed that remdesivir was not associated with significant clinical benefits in their trial, but they noted that "the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies."
Meanwhile, a separate report said early results from another study conducted at the University of Chicago had found that COVID-19 patients, most with severe disease, who were given remdesivir "[saw] rapid recoveries in fever and respiratory symptoms."
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