FDA Approves Remdesivir for Treatment of COVID-19

Officials with the FDA have approved Gilead’s remdesivir (Veklury) for the treatment of coronavirus disease 2019 (COVID-19), making it the first FDA-approved treatment for the disease, the company announced.

Remdesivir was granted emergency use authorization (EUA) by the FDA back in May and given to President DonaldTrump after he was diagnosed with COVID-19 earlier this month.

Remdesivir is indicated for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of COVID-19 requiring hospitalization. According to Gilead, remdesivir should only be administered in a hospital or in a health care setting capable of providing acute care comparable to inpatient hospital care.

Along with the approval, the FDA also issued a new EUA for the use remdesivir to treat hospitalized pediatric patients under 12 years of age weighing at least 3.5 kg or hospitalized patients weighing 3.5 kg to less than 40 kg with COVID-19 for whom use of an intravenous agent is clinically appropriate.

In a previous interview with Drug Topics® conducted when remdesivir was still only authorized for emergency use, Julie Ann Justo, PharmD, infectious diseases clinical pharmacist and associate professor at the University of South Carolina College of Pharmacy, discussed the drug as a potential treatment for COVID-19.

“Originally, most people will be familiar with it as it was an investigational agent in the treatment of Ebola virus,” Dr Justo told Drug Topics®. “Remdesivir itself, its purported mechanism of action, it’s a nucleotide analogue that is going to disrupt viral replication at the RNA polymerase.”

“When the virus is inside the human cell and trying to hijack and increase its own replication, remdesivir is theorized to block that replication, starting relatively early on in the disease course of the SARS-CoV-2 virus.”

Over the past couple of months, remdesivir emerged as one of the more promising treatments for COVID-19. However, just last week, interim results from the World Health Organization's Solidary Therapeutics Trial suggested that remdesivir, along with hydroxychloroquine, lopinavir/ritonavir, and interferon regimens, appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalized patients. The purpose of the study, which spans more than 30 countries, was to examine the effects of repurposed drugs for the treatment of COVID-19.²

In a statement responding to the Solidarity Trial results, Gilead said, "The emerging data appear inconsistent with more robust evidence from multiple randomized, controlled studies published in peer-reviewed journals validating the clinical benefit of Veklury (remdesivir)."³

The FDA’s approval is based on data from 3 randomized controlled trials, including the phase 3 ACTT-1 trial, which showed that treatment with remdesivir resulted in clinically meaningful improvements across multiple outcome assessments compared with placebo in hospitalized patients with the disease.

The ACTT-1 study evaluated the efficacy and safety of a 10-day treatment course of remdesivir versus placebo in 1063 hospitalized adults with mild, moderate, or severe COVID-19 who were also receiving standard-of-care treatment.

Results of the study showed that remdesivir significantly improved time to recovery 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). Additionally, remdesivir 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), according to the study.

Two other phase 3 trials, SIMPLE-Severe and SIMPLE-Moderate, examined the use of remdesivir in adult patients with severe and moderate COVID-19, respectively. In the SIMPLE-Severe study, conducted in hospitalized patients who required supplemental oxygen and who were not mechanically ventilated, the results showed 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). In the SIMPLE-Moderate trial, which was conducted in hospitalized patients who did not require supplemental oxygen, the results demonstrated statistically improved clinical outcomes with a 5-day treatment course compared with standard of care (odds ratio 1.65; 95% CI, 1.09 to 2.48; p=0.017).

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.

In terms of adverse effects (AEs), the most commonly reported AEs in study participants in the SIMPLE-Severe in either the 5-day or 10-day treatment group were nausea, AST increased, and ALT increased. In the SIMPLE-Moderate trial, the most common AE was nausea.

“I think for pharmacists, the biggest thing to remember is not to lose sight of our original purpose, which is to optimize therapy for our patients,” Dr Justo previously told Drug Topics®. “It’s very important to understand the background pharmacology of this agent, which is readily available, and the FDA factsheet that’s been provided for health care providers. I encourage pharmacists, physicians, and other folks that will be interacting with and using this medication in patients to read that and be familiar with that so they can properly both dispense the medication, administer the medication, and then also to counsel patients and families.”

Reference

1. U.S. Food and Drug Administration Approves Gilead’s Antiviral Veklury® (remdesivir) for Treatment of COVID-19. News release. Gilead; October 22, 2020. 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. Solidarity Therapeutics Trial produces conclusive evidence on the effectiveness of repurposed drugs for COVID-19 in record time. News release. World Health Organization; October 15, 2020. Accessed October 22, 2020. https://www.who.int/news/item/15-10-2020-solidarity-therapeutics-trial-produces-conclusive-evidence-on-the-effectiveness-of-repurposed-drugs-for-covid-19-in-record-time

3. Gilead Sciences Statement on the Solidarity Trial. Company statement. Accessed October 22, 2020. https://www.gilead.com/news-and-press/company-statements/gilead-sciences-statement-on-the-solidarity-trial