The drug remdesivir has been under the spotlight as a possible treatment for critical cases of novel coronavirus disease (COVID-19). Globally, it is one of the four possible lines of treatment being investigated in the Solidarity trials under the aegis of the World Health Organization (WHO). While the drug is yet to get approval in any country to treat COVID-19, recent studies have claimed they have found promising results.
What is remdesivir?
It is a drug with antiviral properties that was manufactured by US-based biotechnology company in 2014, to treat Ebola cases. It was also tried in patients of MERS and SARS, both caused by members of the coronavirus family, but experts said it did now show promising results back then.
Coronaviruses have a single-strand RNA as their genetic material. When the novel coronavirus SARS-CoV2 enters a human cell, an enzyme called RdRP helps the virus replicate. Remdesivir works by inhibiting the activity of RdRP.
Infectious disease expert Dr Tanu Singhal said, “When the virus engulfs itself around a human cell, it injects its RNA inside the cell. The RdRp enzyme causes viral replication. Remdesivir inhibits the enzyme and stops further replication.”
What have studies found?
A small cohort study published in The New England Journal of Medicine on April 10 used remdesivir on 61 patients in USA, Canada, Europe and Japan. These patients were critically ill with low oxygen levels, and were administered remdesivir under manufacturer Gilead’s compassionate use programme. Each patient was administered a 10-day course of remdesivir — 200 mg on the first day and 100 mg each on the other nine days. Of them, 53 patients were studied. The study found clinical improvement in 68% of the cases, with their oxygen levels improving; 47% patients could be discharged after treatment, and more than 50% patients (17 of 30) no longer required mechanical ventilator support. The study found that clinical improvement was less frequent in patients on invasive ventilators or among elderly people. Seven patients died despite treatment with remdesivir.
Another study, published on April 13 in the Journal of Biological Chemistry by researchers from the University of Alberta, reported promising results but not in patients. The researchers conducted a laboratory study in which the drug was able to prevent the virus from replicating.
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The lab study also targeted the enzyme that drives the virus’s replication in the body. Matthias Götte, chair of medical microbiology and immunology at the University of Alberta, said that remdesivir tricks the virus by mimicking its building blocks. “These coronavirus polymerases (RdRP enzymes described above) are sloppy and they get fooled, so the inhibitor gets incorporated many times and the virus can no longer replicate,” Götte said in a statement.
How promising are these results?
No study on remdesivir so far has been large enough to be viewed with credibility. The study published in The New England Journal of Medicine looked at 53 patients, who represent too small a cohort to draw definitive conclusions. Also, 13% of the patients in the study died.
The study had no control arm, meaning another group of patients who were not administered the drug, to compare outcomes of treatment with and without remdesivir. Unless such trials are conducted, the effect of the drug remains a grey zone.
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The study’s lead author, Jonathan D Grein, director of hospital epidemiology, Cedars-Sinai Medical Center, Los Angeles, said “no definitive conclusions can be drawn from these data” but he encouraged further controlled trials to validate the treatment potential of remdesivir.
Dr Harshad Limaye of the internal medicine department in Mumbai’s Nanavati Hospital, a designated COVID-19 hospital, said remdesivir did not show great results with Ebola either. “But the Ebola and coronavirus are different. We should wait for the trials to measure the efficacy of the drug for COVID-19,” Dr Limaye said.
What is India’s stand on remdesivir?
The Indian Council of Medical Research (ICMR) has said it can consider using the drug if local manufacturers are willing to procure it. Remdesivir is currently not available in India. The ICMR plans to wait and watch for the results of WHO’s Solidarity trials to make an assessment on the efficacy of remdesivir for COVID-19 treatment.
Where else in remdesivir being studied?
Currently, there are about six trials and studies being done globally for remdesivir. China has initiated two clinical trials using remdesivir in multiple sites in Hubei province, the worst hit with COVID-19. One study will focus on critically ill patients with low oxygen levels. The other study will focus on patients with moderate symptoms.
In the US, the National Institutes of Health has started a phase-II randomised placebo-controlled trial for adult patients. In France, the INSERM research institute is conducting a study to evaluate potential treatments for COVID-19; these include remdesivir.
Gilead is also running a phase-III trial in the US, Asia and Europe.
What are the other lines of treatment being investigated?
Hydroxychloroquine, an anti-malarial drug, is undergoing multiple trials to assess if it can be used to treat severe COVID-19 cases. It works by decreasing the acidity in parts of the cell where the virus is present, thereby inhibiting it.
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Again, ritonavir and lopinavir are two antiviral drugs used for treatment of HIV. These too work by inhibiting the virus;s RNA. Specifically, they target the enzyme that helps the virus split proteins.
These two drugs are being used in India and several countries for seriously ill patients. In HIV patients, these two antiviral drugs work together to decrease the viral load in blood. Their use in COVID-19 patients seeks the same outcome. “But so far, it has not shown great success in viral suppression,” said Dr Pravin Amle, infectious disease expert. He relies on the antibiotic azithromycin as his first choice.
In Wuhan, a clinical trial on 199 patients published in The New England Journal of Medicine on March 18 did not find a clinical difference between patients given ritonavir-lopinavir and those not given the combination.
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