It began life as an antiviral drug for Hepatitis C and Ebola and was also tested for SARS and MERS, but it was only when the COVID-19COVID-19COVID-19 pandemic swept the world that Remdesivir truly became a household name.

The drug became a part of the COVID-19 treatment in many countries as an experimental therapy for moderate cases (those on oxygen), and it continues to be used widely among patients. It was part of the treatment extended to US President Donald Trump after he was diagnosed with COVID-19 late in September.

However, there have been questions regarding its use since July, when the some countries began a review of Remdesivir amid reports of its adverse effects, especially on the liver, among patients. 

The confusion intensified in October as interim results from the WHO’s Solidarity Trial — which is aimed at zeroing in on an effective Covid treatment — said Remdesivir and three other drugs “appeared to have little or no effect on hospitalised COVID-19 patients, as indicated by overall mortality, initiation of ventilation and duration of hospital stay”. 

Just a week later, the US Food & Drug Administration (FDA) approved Remdesivir for use among coronavirus patients subject to certain conditions, making it the first treatment for COVID-19 to receive the watchdog’s approval. 

The controversy around the use of Remdesivir stems from divergent claims about its efficacy among patients, and appears to centre on the stage at which it should be administered to patients.

Here is how science explains Remdesivir, and why there are different assessments about its efficacy.

How does Remdesivir work

A virus is not strictly a living organism. It cannot replicate unless it has entered a host cell. Once it does, the virus uses the genetic material of the host cell to make multiple copies of itself and then goes on to invade other cells, repeating the process till the “viral load” is high enough for the body to start showing symptoms of the infection. 

When Remdesivir enters a cell, it mimics some of the viral material that is used to make copies of the virus, thus disrupting the copying process. This can, however, only work when the virus is still new to the body and has not made enough copies of itself to invade multiple sites in the body. It won’t work if the body’s immune system has started becoming hyperactive because of the viral load.

In some countries, it is recommended that Remdesivir should not be used if a patient with COVID-19 displays signs of liver damage, has severe renal impairment, is pregnant or lactating, and less than 12 years old. 

Even Gilead, in its safety summary about the drug, mentions the possibility of elevated liver enzymes in patients taking the drug.

The controversy

On 15 October, a preprint on the interim results of the WHO’s Solidarity trial — meant to study the impact of four drugs on mortality from COVID-19 — said Remdesivir and three other drugs “appeared to have little or no effect on hospitalised COVID-19 patients, as indicated by overall mortality, initiation of ventilation and duration of hospital stay”.  

Gilead Sciences, the American firm that first manufactured the drug, strongly contested the findings, pointing out in a statement that the study was not peer-reviewed, and that there is “more robust evidence from multiple randomised, controlled studies published in peer-reviewed journals validating the clinical benefit of Veklury® (Remdesivir)”.

“The benefits of Veklury have been demonstrated in three randomised, controlled clinical trials, including a randomised, double-blind, placebo-controlled clinical trial (ACTT-1) — the gold standard for evaluating the efficacy and safety of investigational drugs. The results from the National Institute for Allergy and Infectious Diseases (NIAID)’s ACTT-1 trial, which was conducted primarily in the United States and Europe, found that treatment with Veklury resulted in clinically meaningful improvements across multiple outcome assessments in hospitalized COVID-19 patients,” Gilead said.

The NIAID study was published in the New England Journal of Medicine this month. It concluded that Remdesivir is superior to placebo in shortening the time to recovery in adults who were hospitalized with COVID-19 and had evidence of lower respiratory tract infection.

On 22 October, the US Food & Drug Administration approved Remdesivir for use among Covid patients subject to certain conditions. The approval of Veklury, the FDA said, was supported by the agency’s analysis of data from three randomised, controlled clinical trials that included patients hospitalized with mild-to-severe COVID-19.

The drug was already in use in the US under emergency use authorization. 

When initially Remdesivir was included in COVID-19 treatment, its use was suggested for moderate patients who are on oxygen.

Some doctors said they have seen patients with mild and moderate disease improve with the drug.

In India where Remdesivir is used for months to treat patients, one doctor said “the drug does not seem to work in really severe patients. But the unfortunate thing is, without a trial, there is no way of ascertaining whether it (recovery) was because of the drug or not. In a viral disease, quite a few patients improve on their own,” he added. 

“In mild or moderate disease, when the patient is on oxygen, we used Remdesivir with several other medicines including steroids and anti-clotting agents. It is difficult to say which of these medicines work. There is also the theoretical possibility that the patient would have got better anyway without any medicine. In a private setup when we are pushed to the wall, we use it, often the families insist,” he said.

Microbiologist Dr Gagandeep Kang, currently attached to Christian Medical College Vellore, said that the failure of Remdesivir “to prevent mortality in the Solidarity trial” does not mean it does “not work at all to treat illness or progression to severe disease”.

Remdesivir was shown not to prevent mortality in the Solidarity trial. Does this mean that Remdesivir does not work at all to treat illness or progression to severe disease? It does not, since that is not what Solidarity was set up to measure.

 “If an antiviral works well to suppress replication of the virus when given early after infection, it may well not work when given at a later stage because symptoms, severity and consequent mortality may be because of host response,” the microbiologist added.

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