VOLUME 43 : NUMBER 5 : OCTOBER 2020
NEW DRUGS

Remdesivir
Aust Prescr 2020;43:176–7

Approved indication: COVID-19

https://doi.org/10.18773/austprescr.2020.060

Veklury (Gilead)vials containing 100 mg powder or 100 mg/20 mL
concentrateFirst published
18 August 2020

Remdesivir, an antiviral originally designed to target
the Ebola virus, has been provisionally approved for
COVID-19. It is indicated for adults and adolescentswith pneumonia who require supplemental oxygen.
Remdesivir is a nucleotide analogue that delays
replication of viral RNA. It comes in the form of aprodrug which is metabolised to the active form
(remdesivir triphosphate) once it enters cells. In vitro
studies have shown that it has antiviral activity against
the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).1
There have been several studies of remdesivir in
hospitalised patients with COVID-19. These haveincluded a compassionate use program,2 twoplacebo‑controlled trials3,4 and two dosing trials5,6(see Table). Apart from the placebo-controlled trialin China,4 all of these studies are ongoing and results
are preliminary.

Some of the views
expressed on newly
approved products
should be regarded as
preliminary, as there
may be limited publisheddata at the time of
publication, and little
experience in Australia of
their safety or efficacy.
However, the Editorial
Executive Committee
believes that comments
made in good faith at
an early stage may still
be of value. Before new
drugs are prescribed,
the Committee believes
it is important that moredetailed information
is obtained from the
manufacturer’s approved
product information,a drug information
centre or some otherappropriate source.

176

The studies enrolled patients with severe disease
and an oxygen saturation of 94% or less, except theunpublished dosing trial which enrolled patients withmoderate disease.6 All except the dosing studies
included (some) patients who required mechanicalventilation. Trials assessed a 10-day intravenous
course of remdesivir starting with a loading dose of
200 mg on day 1 followed by 100 mg on subsequentdays. The two dosing trials compared a 10-day coursewith a 5-day course of remdesivir.5,6
The Adaptive COVID-19 Treatment Trial found thatpatients receiving remdesivir recovered faster thanthose receiving placebo (median of 11 days vs 15days).3 However, in the Chinese placebo-controlled
trial, remdesivir was not associated with a statisticallyshorter time to clinical improvement compared toplacebo (median 21 days vs 23 days). This trial was
terminated early due to control of the outbreak,therefore its statistical power was reduced from
80% to 58%.4
The dosing trials5,6 compared a 5-day course ofremdesivir with a 10-day course. One of the trials
reported no statistical difference in clinical benefit
between the two durations. There was no placebo
arm in this trial so the magnitude of the clinicalbenefit could not be quantified.5
The other dosing trial6 included a standard of carearm as a control. Enrolled patients were hospitalised

Full text free online at nps.org.au/australian-prescriber

with moderate disease (pneumonia without reduced
oxygen saturation). At 11 days, clinical improvement
was statistically better in patients who received the5-day course, but not the 10-day course, compared tostandard of care (see Table). These results have notyet been published in a peer-reviewed journal.
In terms of safety, increased liver enzymes arevery common with remdesivir. It is therefore notrecommended in people with elevated alanine
aminotransferase (≥5 times the upper limit of normal).
Headache, nausea and rash were common adverse
events in the trials.
Remdesivir is a category B2 drug in pregnancy.
Over 300 pregnant women have received it througha compassionate use program but there are nosafety data available from this so far. Animal studies
show that a metabolite of remdesivir is excreted
in breastmilk.
Remdesivir is administered by an intravenous infusion.
Peak plasma concentrations are reached 1.5–5 hours
after the start of the infusion. Most of the dose is
excreted as metabolites in the urine (74%) and faeces(18%). This product contains the excipient sulfobutyl
betadex sodium which is renally cleared. As thisaccumulates in people with impaired kidney function,remdesivir is not recommended when the estimatedglomerular filtration rate is less than 30 mL/min.
Drug–drug interaction studies have not been
carried out with remdesivir so the potential forinteractions is not known. In vitro studies suggestthat strong inhibitors and inducers of cytochrome
P450 (CYP) enzymes 2C8, 2D6 and 3A4 may affectremdesivir plasma concentrations. Concomitanthydroxychloroquine or chloroquine is notrecommended due to possible antagonism.
Remdesivir seemed to be marginally better thanplacebo or standard of care in patients with severe
COVID-19 in some of the clinical trials but not others.
However, clinical data are limited and most results arepreliminary. More comprehensive evidence of benefit
is awaited by the Therapeutic Goods Administration.
At this stage, the Australian guidelines for the clinicalcare of people with COVID-19 give a conditional
recommendation for remdesivir stating that, wherepossible, remdesivir should be used in the context
of a clinical trial but can be considered outside of atrial setting for patients with moderate, severe andcritical COVID-19. However, they do warn against its
routine use in pregnant and lactating women outsideof a trial.
T T manufacturer provided additional useful
information© 2020 NPS MedicineWise

VOLUME 43 : NUMBER 5 : OCTOBER 2020
NEW DRUGS

Table Efficacy of the antiviral remdesivir* for severe COVID-19
Trial

Study arms

Efficacy

Mortality

Compassionate use
program (single-arm)2

Remdesivir for 10 days
(53 patients)

Clinical improvement interms of oxygen requirement:
68% of patients improved,
15% got worse

13% after a median of
15 days of treatment

Placebo-controlled trial(Adaptive COVID-19
Treatment Trial)3

Remdesivir (538 patients)
vs placebo (521 patients)for 10 days

Median time to recovery:†11 vs 15 days (rate ratio 1.32,
CI 1.12–1.55 P<0.001)

7.1% vs 11.9% at 14 days
(HR 0.7, CI 0.47–1.04)

Placebo-controlled trial(in Hubei, China) †† 4

Remdesivir (158 patients)
vs placebo (78 patients)for 10 days

Median time to clinicalimprovement: 21 vs 23 days
(HR 1.23, CI 0.87–1.75)

14% vs 13% at 28 days

Open-label, randomised
dosing trial ‡ 5

Remdesivir for 10 days
(197 patients) vs 5 days
(200 patients)

Clinical improvement of 2 points
on a 7-point scale:§ 54% vs 65%

11% (10 days) vs 8%(5 days)Remdesivir for 10 days
(193 patients) vs 5 days
(191 patients) vs standardof care (200 patients)

Clinical improvement on a
7-point scale§ compared tostandard of care at day 11:

Open-label, randomised
dosing trial withstandard of care arm # 6

Median time to recovery:
11 vs 10 days
1% (10 days) vs0% (5 days) vs 2%(standard of care)• 5-day course – OR 1.65
(CI 1.09–2.48, p=0.17)• 10-day course – OR 1.31
(CI 0.88–1.95, p=0.18)

CI confidence intervals, HR hazard ratio, OR odds ratio* Patients received a loading dose of 200 mg on day 1 followed by 100 mg a day after that.
† Recovery defined as hospital discharge or hospitalisation for infection control purposes only.
†† Concomitant treatments for COVID-19 were allowed including lopinavir/ritonavir, interferons and corticosteroids.
‡ Patients receiving mechanical ventilation were not included in this trial.
§	1=death, 2=hospitalised and receiving invasive ventilation, 3=hospitalised receiving non-invasive ventilation or highflow oxygen, 4=hospitalised receiving low-flow oxygen, 5=hospitalised with no oxygen requirement but needing
medical care, 6=hospitalised with no oxygen or medical care needed, 7=not hospitalised# Patients had moderate disease (pneumonia without reduced oxygen saturation).

REFERENCES
1.

2.

3.

4.

5.

6.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al.
Remdesivir and chloroquine effectively inhibit the recently
emerged novel coronavirus (2019-nCoV) in vitro. Cell Res
2020;30:269-71. https://doi.org/10.1038/s41422-020-0282-0
Grein J, Ohmagari N, Shin D, Diaz G, Asperges E,Castagna A, et al. Compassionate use of remdesivir forpatients with severe Covid-19. N Engl J Med 2020;382:2327-36.
https://doi.org/10.1056/NEJMoa2007016
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS,Kalil AC, et al. Remdesivir for the treatment of Covid-19 –preliminary report. N Engl J Med. Epub 2020 May 20.
https://doi.org/10.1056/NEJMoa2007764
Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir
in adults with severe COVID-19: a randomised, double-blind,placebo-controlled, multicentre trial. Lancet 2020;395:1569-78.
https://doi.org/10.1016/S0140-6736(20)31022-9
Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R,
Montejano R, et al. Remdesivir for 5 and 10 days in patientswith severe Covid-19. N Engl J Med. Epub 2020 May 27.
https://doi.org/10.1056/NEJMoa2015301
ClinicalTrials.gov. Study to evaluate the safety and antiviral
activity of remdesivir (GS-5734™) in participants withmoderate coronavirus disease (COVID-19) compared tostandard of care treatment. ClinicalTrials.gov Identifier:
NCT04292730. Updated 2020 Jul 27. https://clinicaltrials.gov/
ct2/show/record/NCT04292730 [cited 2020 Aug 13]

The Transparency Score is explained in New drugs:
transparency, Vol 37 No 1, Aust Prescr 2014;37:27.
At the time the comment was prepared, information
about this drug was available on the websites of theFood and Drug Administration in the USA, and theEuropean Medicines Agency and the TherapeuticGoods Administration.

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