Officials with the FDA have approved the antiviral drug remdesivir (Veklury, Gilead Sciences) for the treatment of patients with the coronavirus disease 2019 (COVID-19) requiring hospitalization.1,2 Previously granted Emergency Use Authorization (EUA) by the FDA,1 remdesivir is now the only approved COVID-19 treatment in the United States.1,2

Remdesivir is indicated for patients aged 12 years and older and weighing at least 40 kg or about 80 pounds.1,2 According to Gilead, the drug works to stop replication of SARS-CoV-2, the virus that causes COVID-19.1 Remdesivir should only be administered in a hospital or in a health care setting capable of providing acute care comparable to inpatient hospital care.1,2

In addition to the FDA’s approval, a revised EUA has been issued for the use of remdesivir to treat hospitalized pediatric patients under age 12 years and weighing at least 3.5 kg or hospitalized pediatric patients weighing 3.5 kg to less than 40 kg with suspected or laboratory confirmed COVID-19 for whom use of an intravenous agent is clinically appropriate. This EUA is temporary, and does not take the place of the formal submission, review and approval process for the use of remdesivir in the patient population under age 12 years.1,2

Remdesivir is now widely available in hospitals across the country, following early steps taken to rapidly expand manufacturing capacity and increase supply.1

“The FDA is committed to expediting the development and availability of COVID-19 treatments during this unprecedented public health emergency,” said FDA Commissioner Stephen M. Hahn, MD, in a prepared statement. “Today’s approval is supported by data from multiple clinical trials that the agency has rigorously assessed and represents an important scientific milestone in the COVID-19 pandemic.2 

Under the Federal Food, Drug, and Cosmetic Act, approval of a new drug product requires substantial evidence of effectiveness and a demonstration of safety for the drug’s intended use(s). In considering approval of a drug, the FDA conducts a benefit-risk assessment based on rigorous scientific standards to ensure that the product’s benefits outweigh its risks for the intended population.2 

“The approval of [remdesivir] marks an important milestone in efforts to help address the pandemic by offering an effective treatment that helps patients recover faster and, in turn, helps preserve scarce health care resources,” said Barry Zingman, MD, professor of medicine at the Albert Einstein College of Medicine and Montefiore Medical Center, New York, in a prepared statement.1

“The availability of a rigorously tested treatment that can significantly speed recovery and offers other benefits such as lower rates of progression to mechanical ventilation, provides hospitalized patients and their families important hope and offers health care providers a critical tool as they care for patients in need,” said Zingman.1

The FDA’s approval of remdesivir is based on 3 randomized controlled trials including the National Institute of Allergy and Infectious Diseases’ (NIAID) double blind, placebo-controlled phase 3 ACTT-1 trial.1,2 The ACTT-1 trial showed that treatment with remdesivir resulted in clinically meaningful improvements across multiple outcome assessments compared with placebo in hospitalized patients with COVID-19. Based on the strength of these data, remdesivir has become a standard of care for the treatment of COVID-19 in hospitalized patients.1

In the ACTT-1 trial, remdesivir significantly improved time to recovery as compared to placebo by 5 days in the overall study population (10 vs. 15 days; rate ratio, 1.29; 95% CI, 1.12 to 1.49; p<0.001) and 7 days in patients who required oxygen support at baseline (11 vs. 18 days; rate ratio, 1.31; 95% CI, 1.12 to 1.52). As a secondary endpoint, remdesivir also reduced disease progression in patients needing oxygen, resulting in a significantly lower incidence of new mechanical ventilation or ECMO (13% vs. 23%; 95% CI, -15 to -4). In the overall patient population, there was a trend toward reduced mortality with remdesivir compared with placebo at day 29 (11.4% vs. 15.2%, HR 0.73; 95% CI, 0.52 to 1.03).1

The ACTT-1 trial results are complemented by results of a pair of phase 3 open-label trials of remdesivir conducted in adult patients with severe and moderate COVID-19. The SIMPLE-Severe trial, conducted in hospitalized patients who required supplemental oxygen and who were not mechanically ventilated, found that a 5-day or a 10-day treatment course of remdesivir achieved similar clinical outcomes (odds ratio 0.75; 95% CI, 0.51 to 1.12). The SIMPLE-Moderate trial, conducted in hospitalized patients who did not require supplemental oxygen, showed statistically improved clinical outcomes with a 5-day treatment course of remdesivir compared with standard of care (odds ratio 1.65; 95% CI, 1.09 to 2.48; p=0.017). According to Gilead, the odds of improvement in clinical status with the 10-day treatment course of remdesivir versus standard of care were also favorable, trending toward but not reaching statistical significance (odds ratio 1.31; 95% CI, 0.88 to 1.95).1

The incidence of adverse events (AEs) associated with remdesivir was similar to placebo in the ACTT-1 trial. Rates of serious AEs were numerically higher in the placebo group compared with the remdesivir group. Treatment discontinuation, all-cause grade 3 and 4 AEs, and laboratory abnormalities were similar across groups. In the SIMPLE-Severe trial, the most common AEs occurring in at least 5% of subjects in either the remdesivir 5-day or 10-day group, respectively, were nausea (5% vs 3%), aspartate aminotransferase increased (3% vs 6%), and alanine aminotransferase increased (2% vs 7%). In the SIMPLE-Moderate trial, the most common AEs occurring in at least 5% of subjects in the remdesivir groups was nausea (7% in the 5-day group, 4% in the 10-day group).1

According to Hahn, as part of the agency’s Coronavirus Treatment Acceleration Program, the FDA will to continue to help move new medical products to patients as soon as possible while also determining whether they are effective and if their benefits outweigh their risks.2


REFERENCES
 
  1. U.S. Food and Drug Administration Approves Gilead’s Antiviral Veklury® (Remdesivir) for Treatment of COVID-19 [news release]. Foster City, CA; October 22, 2020: Gilead Sciences. Accessed October 22, 2020. https://www.gilead.com/news-and-press/press-room/press-releases/2020/10/us-food-and-drug-administration-approves-gileads-antiviral-veklury-remdesivir-for-treatment-of-covid19
  2. FDA Approves First Treatment for COVID-19 [news release]. Silver Spring, MD; October 22, 2020: FDA. Accessed October 22, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19