The FDA also expanded the pediatric emergency use authorization for remdesivir to include the treatment of non-hospitalized pediatric patients at high risk of disease progression.
The FDA has approved remdesivir (Veklury; Gilead) for the treatment of patients with COVID-19 who are not hospitalized but who have high risk for disease progression, including hospitalization or death. In addition to the approval, officials with the FDA expanded the pediatric emergency use authorization (EUA) to include the treatment of non-hospitalized pediatric patients at high risk of disease progression.
According to a press release, the approval is based on phase 3 data from the PINETREE trial showing that treatment with remdesivir significantly reduced the risk of hospitalization by 87% compared with placebo. Remdesivir is the antiviral standard of care for the treatment of patients hospitalized with COVID-19, and guidelines from the National Institutes of Health also recommend remdesivir for the treatment of non-hospitalized patients at high risk.
With this approval, remdesivir can be administered in qualified outpatient settings that are able to administer daily intravenous infusions over 3 consecutive days. The approval and EUA expansion come in response to the surge in COVID-19 cases and the reduced susceptibility to several anti-SARS-CoV-2 monoclonal antibodies due to the omicron variant, according to the press release.
Unlike the monoclonal antibodies, remdesivir targets the highly conserved viral RNA polymerase, which allows it to retain activity against existing SARS-CoV-2 variants of concern. In vitro laboratory testing has found that remdesivir retains activity against the omicron variant, as well. No major genetic changes have been identified in any known variants of concern that would significantly alter the viral RNA polymerase targeted by remdesivir, according to Gilead.
“Remdesivir has now helped to treat more than 10 million people around the world with COVID-19 and continues to play a key role in helping to reduce the burden of the pandemic,” said Daniel O’Day, chairman and CEO of Gilead Sciences, in the press release. “Based on the most recent data, we now understand that remdesivir is also effective in the early stages of COVID-19 infection, in addition to helping patients who are hospitalized with the disease.”
PINETREE was a randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of a 3-day course of remdesivir for intravenous use for the treatment of COVID-19 in non-hospitalized patients at high risk for disease progression. An analysis of 562 participants randomly assigned 1:1 to receive either remdesivir or placebo found that treatment with remdesivir resulted in a statistically significant 87% reduction in risk for the composite primary endpoint of COVID-19-related hospitalization or all-cause death by day 28 compared with placebo. According to the press release, no deaths were observed in either arm of the trial by day 28.
Furthermore, the safety profile was similar between remdesivir and placebo across the variety of outpatient settings. The most common treatment emergent adverse events in patients taking remdesivir were nausea and headache.
In the United States, remdesivir is indicated for the treatment of adult and pediatric patients 12 years of age and older who are either hospitalized or not hospitalized and are at high risk for progression to severe COVID-19. It is additionally authorized for these uses under the EUA for pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg.
The recommended treatment duration for non-hospitalized patients with confirmed SARS-CoV-2 at high risk of progression is 3 days. However, the recommended duration for hospitalized patients not on mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) is 5 days, with the option to extend to a total of 10 days as needed. Critically ill patients who require mechanical ventilation and/or ECMO should receive a 10-day course of treatment, according to Gilead.
“While we continue to advance remdesivir to benefit more patients in multiple settings, we are also advancing our investigational oral compounds,” O’Day said in the press release. “These are based on the same antiviral mechanism of action as remdesivir and a phase 1 trial of our oral COVID-19 antiviral, GS-5245, is now underway.”
FDA Approves Veklury (Remdesivir) for the Treatment of Non-Hospitalized Patients at High Risk for COVID-19 Disease Progression. News release. Gilead; January 21, 2022. Accessed January 24, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/1/fda-approves-veklury-remdesivir-for-the-treatment-of-nonhospitalized-patients-at-high-risk-for-covid19-disease-progression