By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved remdesivir, the first treatment for COVID-19. This comes about six months after the agency granted an Emergency Use Authorization (EUA) in May 2020. Remdesivir is an antiviral acting as a SARS-CoV-2 nucleotide analog RNA polymerase inhibitor. It is distributed as Veklury.
Remdesivir should be prescribed to treat COVID-19 in adults and pediatric patients ≥ 12 years of age and weighing at least 40 kg who need hospitalization.1 The agent should be used in a hospital or an equivalent inpatient care setting.
The recommended dose is a 200-mg single loading dose on day 1 delivered through intravenous infusion (30 minutes to 120 minutes).1 From day 2 on, follow a once-a-day maintenance dose of 100 mg. The recommended duration is five days if extracorporeal membrane oxygenation and/or invasive mechanical ventilation is not required. If clinical improvement is not achieved, duration may be extended to 10 days. For those requiring invasive mechanical ventilation, remdesivir should be given for 10 days. Because of the risk of reduced antiviral activity, co-administration with chloroquine or hydroxychloroquine is not recommended.1 Remdesivir is available as a 100-mg, single-dose vial.
Remdesivir is the only drug and only antiviral agent approved for COVID-19.
Remdesivir has not been proven to reduce overall mortality caused by COVID-19. Hypersensitivity reactions, including anaphylactic reactions, have been observed during and following administration.1 Increased risks of transaminase elevations also have been reported.1
Remdesivir’s approval was based on data from three randomized trials.1 The first, performed by the National Institute of Allergy and Infectious Diseases (NIAID), included hospitalized subjects with mild/moderate and severe COVID-19 and evidence of lower respiratory tract infection.1,2 The May 2020 EUA was based on an interim analysis of this study.3 A total of 541 subjects were randomized to remdesivir and 521 to placebo for 10 days. Subjects were stratified into four ordinal hospitalized severity categories (requiring any oxygen, requiring ongoing medical care, requiring use of high-flow oxygen device or requiring noninvasive ventilation, and extracorporeal membrane oxygenation or invasive ventilation). The primary outcome measure was time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. The authors watched for patients who reached one of these ordinal improvements: not hospitalized, and no limitation of activities; not hospitalized, limitation on activities, requiring home oxygen, or both; or hospitalized, not requiring supplemental oxygen, and no longer requiring ongoing medical care. The overall median time to recovery was 10 days on remdesivir vs. 15 days for placebo. In those with severe disease, the median recovery time was 11 days vs. 18 days. Those requiring supplemental oxygen were 45% more likely to benefit from remdesivir. Secondary endpoints were mortality and improvement of one or two categories on the 7-point ordinal severity scale. Mortality rates were not statistically different over the study period. Remdesivir-treated subjects were 50% more likely to improve in ordinal categories.
In an open-label, non-placebo-controlled, study of 397 severe COVID-19 subjects (evidence of pneumonia, oxygen saturation [SpO2] ≤ 94%, or receiving supplemental oxygen at screening), remdesivir (five-day course) showed no difference in improvement in clinical status on day 14 or time to clinical improvement compared to a 10-day course.1,4 There also was no significant difference in all-cause mortality. In another randomized, open-label, three-arm (five-day, 10-day, or standard of care) study of 584 subjects with moderate disease (evidence of pneumonia, SpO2 > 94%), a five-day treatment was better than standard of care in terms of improvement in clinical status on day 11.1 However, no difference was observed for the 10-day course vs. standard of care.1 All-cause mortality at day 28 was ≤ 2% in all groups. The cost for a five-day course of treatment is $3,120.
Remdesivir’s benefit appears to be modest, but may be better for those receiving low-flow oxygen. No mortality benefit has been demonstrated. The World Health Organization conducted an open-label, randomized trial on the effect of four drugs on in-hospital mortality as well as initiation of ventilation or hospitalization duration in more than 11,000 subjects in 30 countries.5 Investigators concluded remdesivir, hydroxychloroquine, lopinavir, or interferon produced little or no benefit. The study has neither been peer reviewed nor published. It has been criticized for its open-label design and for lacking the same level of scientific rigor as the NIAID study.6 Regardless, remdesivir is expected to be used extensively until other therapeutics are available.
- Gilead Sciences, Inc. Veklury prescribing information. October 2020.
- Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19. Final report. N Engl J Med 2020. doi: 10.1056/NEJMoa2007764. [Online ahead of print].
- The National Institute of Allergy and Infectious Diseases. NIH clinical trial shows remdesivir accelerates recovery from advanced COVID-19. April 29, 2020.
- Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med 2020; May 27;NEJMoa2015301. doi: 10.1056/NEJMoa2015301. [Online ahead of print].
- WHO Solidarity trial consortium. Repurposed antiviral drugs for COVID-19 — interim WHO SOLIDARITY trial results. Oct. 15, 2020.
- Keaten J, Marchione M. WHO study finds remdesivir didn’t help COVID-19 patients. The Associated Press. Oct. 16, 2020.