|Year : 2020 | Volume
| Issue : 3 | Page : 96-97
Remdesivir, the magic bullet for COVID-19?
Department of Pharmacology, MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India
|Date of Submission||17-May-2021|
|Date of Decision||27-May-2021|
|Date of Acceptance||08-Jun-2021|
|Date of Web Publication||30-Jun-2021|
Dr. Ipseeta Ray
Professor, Department of Pharmacology, MGM Medical College and Hospital, Navi Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Coronavirus infection, or COVID 19, was originally identified in Wuhan, China, in December 2019, but quickly spread over the world, resulting in a pandemic. Remdesivir, an antiviral agent by inhibiting viral RNA-dependent polymerase enzyme and was earlier used against Ebola, HIV etc, was presumed useful in the quest for a remedy against SARS-CoV-2. Several investigations had shown its promising antiviral properties in vitro and in vivo against severe acute respiratory syndrome due to coronavirus (SARS-CoV-1). Hence, Remdesivir was approved by the US FDA in the second half of 2020, followed by DCGI, for treatment in adults and children with SARS-CoV-2, requiring hospitalisation with moderate to severe symptoms. Pivotal trials (ACTT 1, SIMPLE Severe trial) showed a faster median time to recovery in these patients. However, several studies found no statistically significant difference in time to clinical improvement or mortality between patients who got remdesivir and those who did not. Although it was hailed as a "Miracle medicine" when it was first launched for COVID-19, its limited efficacy may not justify its status as such. The goal of this review is to outline the evidence and clinical studies of remdesivir, as well as its rise and decline as a treatment option.
Keywords: Remdesivir, COVID-19, Antiviral drugs
|How to cite this article:|
Ray I. Remdesivir, the magic bullet for COVID-19?. J Pediatr Assoc India 2020;9:96-7
| Introduction|| |
Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent RNA polymerase, with in vitro inhibitory activity against SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV), was identified early as a promising therapeutic candidate for COVID-19. It was because of its ability to inhibit SARS-CoV-2 in vitro., In addition, in nonhuman primate studies, initiated in 12 h after inoculation with MERS-CoV, remdesivir reduced lung virus load and damage to lungs.
On October 22, 2020, FDA approved remdesivir for use in adults and pediatric patients (12 years of age and weighing at least 40 kg) for treating SARS-CoV-2 who required hospitalization. The Drug Controller General of India (DCGI) also approved remdesivir for restricted emergency use in COVID-19 treatment in India. The approval was part of the DCGI's accelerated approval process to address urgent and unmet needs in pandemic scenario.
| Clinical Evidence|| |
In a Phase 3 adaptive, randomized double-blind placebo-controlled trial (ACTT-1) showed a faster median time to recovery in hospitalized patients (n = 541) receiving remdesivir, as compared to placebo group (n = 521) for 10 and 15 days, with some survival benefit (mortality by day 15 was 6.7% vs. 11.9%). A Phase 3 adaptive randomized double-blind trial then compared remdesivir alone (n = 518) versus a combination regimen of remdesivir and baricitinib (n = 515). There was a better clinical outcome when combined. Analysis of data from Phase 3 SIMPLE-Severe trial and real-world retrospective cohort of patients indicated that remdesivir was associated with reduced mortality and greater recovery rate [Table 1].
Subgroup analyses of data from Phase 3 SIMPLE-Severe trial indicated that response to remdesivir was better among black race, below 65 years of age, treatment outside of Italy, and requiring only low-flow oxygen support on room air at baseline. Further, it was seen that remdesivir with hydroxychloroquine regimen was associated with lower recovery rate at day 14 (57% vs. 69%) and higher risk of ADRs, compared to those treated with remdesivir alone.
A randomized double-blind placebo-controlled trial in hospitalized patients of severe COVID-19 in China showed no statistically significant difference in time to clinical improvement between patients who received remdesivir (n = 158) and patients who received placebo (n = 78) over 21 days versus 23 days. Mortality in 28 days was similar in both the groups (14 vs. 13%). No effect on viral clearance was reported in the study.
[Table 2] summarizes the results of two Phase 3 randomized open-label trials in hospitalized patients of severe COVID-19 not requiring mechanical ventilation sponsored by the manufacturer (Gilead) to compare the effectiveness of 5- versus 10-day administration of remdesivir.
|Table 2: Outcome of SARS-Cov-2 Patients with Remdesivir, as Compared to Standard of Care|
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Solidarity trial – 2743 patients recruited to remdesivir group and 2708 to standard care group. Remdesivir did not reduce mortality, need for initiation of ventilation, and hospital stay in COVID-19 patients.
| Recommendations for Use of Remdesivir in COVID-19|| |
Injection remdesivir 200 mg intravenous (IV) on day 1, followed by 100 mg IV OD (day 2–5).
To consider remdesivir in patients who are reverse transcription–polymerase chain reaction positive for SARS-CoV-2, pneumonia confirmed by chest imaging, oxygen saturation of 94% or lower on room air, or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less and were within 10 days of onset of symptoms.
The role of remdesivir is optimal in the first 10 days. It reduced symptom duration but no benefit in mortality. Computed tomography (CT) severity score more than 8 (out of 25) can also be used in patients with CT severity score less than 8 with dense consolidation (rather than Ground Glass Opacity (GGO)), high fever without raised C-reactive protein (viremia phase), especially in the elderly, and with comorbidities even with normal CT.
Hospitalization is important for all age groups of patients to initiate remdesivir.
| Children|| |
Remdesivir is now available through an Emergency Use Authorization for the treatment of COVID-19 in hospitalized pediatric patients.
It is recommended that remdesivir be used in a restricted manner within 3 days of onset of symptoms after ascertaining that child's renal and liver functions are normal and to be monitored for side effects.
There is no role of remdesivir in mild cases of COVID-19.
Suggested doses (body weight based)
- From 3.5 to 40 kg: 5 mg/Kg I.V. on the 1st day, then 2.5 mg/Kg I.V. once daily for 4 days
- More than 40 Kg body weight: 200 mg I.V. on the 1st day, followed by 100 mg I.V. once daily for 4 days.
| Caution while Using Remdesivir|| |
No data exists about safety in pregnancy or during breastfeeding.
Avoid if hepatic cirrhosis; alanine aminotransferase or aspartate aminotransferase more than five times the upper limit of normal; known severe renal impairment (estimated glomerular filtration rate less than 30 mL/min per 1·73 m2); or receiving continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
However, many centers are using remdesivir, if clearly indicated, in compensated cirrhosis patients, renal compromised patients, and in those on hemodialysis with careful monitoring without any major issues.,,
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[Table 1], [Table 2]