An 800-patient randomized, double-blind, placebo-controlled trial conducted by the National Institute of Allergy and Infectious Diseases (NIAID) has apparently met its primary endpoint of reducing the time to recovery in COVID-19 patients, according to the drug’s manufacturer, Gilead Sciences, in statements just released.
The NIAID, part of the US National Institutes of Health, conducted the study at multiple centers around the US. The primary endpoint of time to recovery was predefined as the first day on which the patient satisfies one of the following three categories:
1) Hospitalized, not requiring supplemental oxygen—no longer requires ongoing medical care;
2) Not hospitalized, limitation on activities and/or requiring home oxygen;
3) Not hospitalized, no limitations on activities1.
“The press release from Gilead previews data that is soon to be released regarding their drug remdesivir as a treatment option for COVID-19 patients. The announcement states that the primary endpoint of time to recovery was reached in a multisite, placebo-controlled, double-blinded control trial that included 800 COVID-19 patients randomized to 10 days of remdesivir versus placebo. We are awaiting the full data on this study,” said Virginia Brady, MD. Dr. Brady is associate editor for Respiratory Medicine for PracticeUpdate and is with Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center in Boston, MA.
The initial sample size was projected to be 572 subjects to achieve 400 subjects with a “recovered” status (per the primary objective). The primary analysis was to be based on 400 recoveries.
Remdesivir or placebo were administered as a 200-mg IV dose followed by a daily 100-mg dose for a total course of 10 days. No data on secondary endpoints such as specific treatment-related improvements or adverse effects are available at this time.
Gilead noted in a press release that “Remdesivir is not yet licensed or approved anywhere globally and has not yet been demonstrated to be safe or effective for the treatment of COVID-19.”2
In a separate press release, Gilead reported results from the phase III SIMPLE trial of approximately 400 patients which compared 5-day versus 10-day dosing of remdesivir3. The company reported similar improvement in clinical status for both doses (OR, 0.75; 95% CI, 0.51–1.12] on day 14) without any new safety signals in either arm.
“These study results complement data from the placebo-controlled study of remdesivir conducted by the National Institute for Allergy and Infectious Diseases and help to determine the optimal duration of treatment with remdesivir. The study demonstrates the potential for some patients to be treated with a 5-day regimen, which could significantly expand the number of patients who could be treated with our current supply of remdesivir,” said Medad Parsey, MD, PhD, the Chief Medical Officer of Gilead, in a press release.
The company also reported that earlier treatment, within 10 days of symptom onset, resulted in 62% of patients being discharged from the hospital at 14 days compared with 49% of patients who were treated with remdesivir more than 10 days after symptom onset.
These potentially positive results from remdesivir in COVID-19 are in line with earlier data reported from an unpublished study conducted by the University of Chicago. The study of 125 patients, of whom 113 had severe disease, seemed to show earlier discharge and reduced mortality4.
Meanwhile, researchers in China found no benefit in a study that ended early because of insufficient subjects.
Remdesivir is a nucleotide analog that is being investigated as a broad-spectrum antiviral agent against COVID-19 in multiple studies around the world as well as against viral pathogens such as Ebola, Marburg, MERS, and SARS.
1. Adaptive COVID-19 Treatment Trial (ACTT); https://clinicaltrials.gov/ct2/show/NCT04280705?term=remdesivir&fund=01&draw=2&rank=2
2. Gilead Sciences Statement on Positive Data Emerging From National Institute of Allergy and Infectious Diseases’ Study of Investigational Antiviral Remdesivir for COVID-19; https://www.gilead.com/news-and-press/press-room/press-releases/2020/4/gilead-sciences-statement-on-positive-data-emerging-from-national-institute-of-allergy-and-infectious-diseases-study-of-investigational-antiviral-rem
3. Gilead Announces Results From Phase 3 Trial of Investigational Antiviral Remdesivir in Patients With Severe COVID-19; https://www.gilead.com/news-and-press/press-room/press-releases/2020/4/gilead-announces-results-from-phase-3-trial-of-investigational-antiviral-remdesivir-in-patients-with-severe-covid-19
4. Early peek at data on Gilead coronavirus drug suggests patients are responding to treatment; https://www.statnews.com/2020/04/16/early-peek-at-data-on-gilead-coronavirus-drug-suggests-patients-are-responding-to-treatment/