Remdesivir’s challenge: treating COVID-19 patients when it could benefit them the most
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Data for Gilead’s remdesivir suggest the antiviral should be used early in the course of COVID-19. Now that the therapy has an EUA from FDA, the challenge will be treating patients with remdesivir when they’re most likely to benefit since it is administered on an in-hospital basis.
The EUA, granted by FDA Friday, covers adults and children hospitalized with lab-confirmed COVID-19 and severe disease. Severe disease is defined as blood oxygen saturation <94% on room air, requiring supplemental oxygen, mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
The agency based its decision on top-line data presented Wednesday from NIH’s randomized, controlled Phase III ACTT study as well as data from Gilead’s Phase III SIMPLE study showing comparable time to clinical improvement in severe COVID-19 patients given remdesivir for five or 10 days (see “Readout for Gilead’s Remdesivir”; “Remdesivir nears regulatory goal line”).
“The NIH study is the first adequately powered and designed study for remdesivir.”
NIAID Director Anthony Fauci said at the time that the preliminary ACTT data showed a “clear-cut significant positive effect in diminishing the time to recovery,” the primary endpoint, vs. placebo (11 vs. 15 days, p=0.001). NIH’s National Institute of Allergy and Infectious Diseases sponsored the study, which enrolled about 800 patients, including those with severe disease (see Table: “Phase III Trials of Remdesivir”).
The ACTT data provided the clearest look yet at the efficacy of the closely watched antiviral, which has been the subject of leaked and accidentally published data. Those reports have been “extremely unhelpful and confusing to the public and the medical community,” Luciana Borio, VP at In-Q-Tel Inc. and former FDA acting chief scientist, told BioCentury.
“The NIH study is the first adequately powered and designed study for remdesivir,” Borio, said. “It shows how important it is to conduct proper clinical trials to give us clear answers about the risks and benefits of promising drugs.”
Fauci called remdesivir the new standard of care for COVID-19 on Wednesday; however, the label appears at odds with data suggesting better outcomes are tied to starting treatment within 10 days of symptom onset.
In SIMPLE, an exploratory analysis showed that 62% of patients treated early vs. 49% of patients treated late were able to be discharged from the hospital.
The EUA suggests both five- and 10-day treatment courses, depending on disease severity.
Data are due late next month from 600 patients in another SIMPLE trial evaluating remdesivir’s effects in moderate COVID-19.
Getting remdesivir to patients
Gilead said Friday that the U.S. government will coordinate the donation and distribution of remdesivir to hospitals in cities most heavily affected by the outbreak. Distribution will be prioritized to hospitals with ICUs or deemed by the government to be most in need.
The company has yet to mention how much it might charge for the therapy.
On the Gilead’s 1Q20 earnings call Thursday, Chairman and CEO Daniel O’Day did not answer multiple questions from investors on the company’s plan to turn a profit from remdesivir.
“It’s too premature,” O’Day said. “Our focus will be on making sure we come up with a sustainable model that allows it to provide remdesivir to patients around the globe, that is intent on providing access and affordability.”
At a White House briefing Friday, O’Day said Gilead is “fully committed to continuing to expand the supply of this medicine.”
The company has been ramping up its manufacturing of the antiviral since the beginning of the year and can now produce the therapy in about 6-8 months, faster than an original estimate of 9-12 months.
“There are plenty of settings where first generation antiviral drugs have been eclipsed by subsequent approvals and I would expect the same thing to happen here.”
Gilead had set a goal of producing at least 500,000 treatment courses by October, 1 million by December and “millions more in 2021, if required.” But that goal were based on a 10-day treatment course. It now expects to be able to stretch that supply further based on the SIMPLE study.
The company said it is forming a consortium of pharmaceutical and chemical manufacturing companies to help it reach its manufacturing goals.
While it has yet to name any partners, the company is in discussions with undisclosed companies to establish end-to-end manufacturing supply chains separate from its own, CFO Andrew Dickinson said on the earnings call. “The difficulty there, as you might imagine, is that given the scarcity of some of the starting materials, we want to make sure that we don’t do anything to impact our supply chain.”
Gilead is looking ahead to developing combination therapies with remdesivir as the base, O’Day said.
Gilead has also been exploring subcutaneous and inhaled formulations of remdesivir for several months, though he declined to provide a timeline. An oral formulation, however, would not be feasible because remdesivir is first metabolized in the liver, he said.
According to BioCentury’s COVID-19 Resource Center, there are more than 350 therapies and vaccines in development for the novel coronavirus.
“This is a first generation antiviral,” former FDA Commissioner Scott Gottlieb told BioCentury on Wednesday. “There are plenty of settings where first generation antiviral drugs have been eclipsed by subsequent approvals and I would expect the same thing to happen here.”
Remdesivir, a nucleotide analog, was developed initially as a treatment for Ebola.
Washington Editor Steve Usdin, Associate Editor Paul Bonanos and Staff Writer Elizabeth S. Eaton contributed to this report.
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