Last week, the US Food and Drug Administration (FDA) gave emergency approval to use the drug remdesivir for critical COVID-19 patients. This came days after Dr Anthony Fauci, director of the US National Institute of Allergies and Infectious Diseases (NIAID), made a strong case for the drug. And yet, also last week, a study published in The Lancet put a question mark about the benefits of using the drug.
What is it about remdesivir that holds promise, and why is it debated?
What is remdesivir?
It was manufactured in 2014 to treat for Ebola, by US-based biotechnology firm Gilead Sciences. It has since been used to treat for MERS and SERS, both caused by members of the coronavirus family. This was, however, not with much success. Current research is looking at whether the drug’s antiviral properties work against SARS-CoV2, the coronavirus that causes COVID-19 disease.
What is the basis of the hopes bing pinned on remdesivir?
SARS-CoV2 replicates itself inside the human cell with the help of an enzyme called RdRp. When remdesivir is injected intravenously, it inhibits this enzyme and effectively blocks replication of the coronavirus. The Journal of Biological Chemistry published a study on April 13 concluding that indeed, the “drug is able to inhibit the virus” and prevent its further spread in human cells.
“Since January, our teams have been working day and night to determine whether remdesivir might work in patients with COVID-19. These efforts include collaboration with study investigators and governments on the various clinical trials. (The) news, that remdesivir might play a role in easing the burden of the pandemic, is the outcome we all hoped would be possible,” Gilead Sciences chairman and CEO Daniel O’Day said.
Remdesivir: Who all are studying it?
There are six major trials or studies under way for remdesivir. It is one of the lines of treatment being investigated under the Solidarity trials under the aegis of the World Health Organization (WHO). Other investigations include Gilead’s own SIMPLE study, the US NIAID’s trials, the French institute Inserm’s DisCoVeRy study, and two clinical trials in China.
On its website, Gilead says it is collaborating with the US FDA, Centers for Disease Control and Prevention (CDC), Department of Health and Human Services, NIAID and Department of Defense-CBRN Medical, the China CDC and National Medical Product Administration (NMPA), WHO, and researchers and clinicians across Europe and Asia to assess the antiviral properties of remdesivir.
The SIMPLE trial is looking at whether a five-day course of remdesivir works as effectively as a 10-day course. Phase-3 results showed that it is indeed so. The trial evaluated 397 patients hospitalised for severe COVID-19 infection. A spokesperson for Gilead said, “This shorter duration of therapy may enable patients to be discharged from the hospital earlier and allow healthcare providers to treat more patients with the existing supply of medication.”
What benefits have been found so far?
Initial trial results made public by NIAID found that mortality rate was 8 per cent in COVID-19 patients administered remdesivir, as opposed to 11.6 per cent in another arm of patients not given this drug. Recovery time improved from 15 to 11 days. The full trial results are yet to be published.
NIAID director Fauci, an immunologist and a member of the US task force against COVID-19, told the media in the White House: “The data shows that remdesivir has a clear cut, significant, positive effect in diminishing the time to recover. Although a 31 per cent improvement does not seem like a knockout 100 per cent, it is a very important proof of concept. What it is proving is that a drug can block this virus.”
A study published in The New England Journal of Medicine on April 10 found clinical improvement in 68 per cent cases with improved oxygen levels after they were administered a 10-day course of remdesivir. The study was, however, of a small cohort of 53 patients and did not have a control arm to compare results for those who were not administered remdesivir.
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Dr Jagmeet Singh, professor of cardiology in Harvard Medical School, suffered from COVID-19 and required ICU support for pneumonia. He is a participant in one of the US trials for remdesivir, although he does not know in which arm he was placed and whether he received the drug. “My response to this drug is somewhat lukewarm. While the drug certainly reduces days of hospitalisation by over 30 per cent and there seems to be some directional evidence in reduction of mortality rate, there is still lack of statistical data to confidently draw conclusions. The Gilead study had no control arm; if it is directional it lacks scientific purity,” he said.
Why is not everyone optimistic?
Some of the trials were limited in scope. Then there was the study in The Lancet on April 29, about a clinical trial of 237 COVID-19 patients in 10 hospitals in China. “In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits,” it said.
The study found adverse drug reaction in 18 people and stopped remdesivir treatment prematurely in them. It said that there were adverse events in 66% of the remdesivir-treated patients.
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Commenting on the study in The Lancet, the Gilead spokesperson said, “The study did not identify any new safety concerns with remdesivir treatment. Cardiac events (cardiac arrest or acute coronary syndrome) and treatment discontinuation due to respiratory failure were events associated with both remdesivir and placebo. The number of patients who completed the study was too low to enable any statistically meaningful conclusions. Data from fully-powered trials are needed to determine the safety profile of remdesivir as treatment for COVID-19.”
To what extent is remdesivir being used in India?
Dr V Ravishankar, chief operating officer in Lilavati Hospital, Mumbai, who until last week had 25 COVID-19 patients, most of them on intensive care support, said doctors in his team are trying ritonavir, lopinavir, and even immunosuppressant tocilizumab, but not remdesivir. “We came across some global reports of adverse reaction of remdesivir in COVID-19 patients. If patients are already critical, we can’t risk experimenting at this stage,” he said.
Dr Jalil Parker, a pulmonologist, said that ideally they wait for sufficient data from clinical trials before using a drug. “But we don’t have many options right now, and we have to try newer drugs for patient with COVID-19. It is doctor’s call whether or not to use the drugs before clinical trial results. I am open to its use.”
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How much of it is available?
Since January, investments have been made to ramp up production and establish a supply chain. Until January there was an inventory to treat 5,000 patients on a 10-day course. By March end, it was scaled up to 30,000 patients. By May end the company plans to produce enough stock for 1.4 lakh patients. Gilead has for now stopped meeting individual requests for supply under its Compassionate Use programme, except for pregnant women and children with severe infection.
The Gilead spokesperson said India is not on its Compassionate Use programme for the drug. “India is part of the large global study designed by the WHO — the Solidarity trial,” the spokesperson said.