Coronavirus (COVID-19) update : #Remdesivir (Gilead Sciences' Drug) and #Coronavirus

Questions:
What is Remdesivir? 0:24
How does Remdesivir work? 1:06
What evidence is there that Remdesivir drug works? 1:40
What is the evidence that Remdesivir does not work? 2:30
What are the problems with trials? 3:38
What is the position of Remdesivir drug in the competition with other drugs for the treatment of coronavirus infection? 4:29

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Dr. Rabindra Tamang
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What is Remdesivir?
It is an experimental antiviral drug developed by the American biopharmaceutical company #Gilead Sciences. It was originally developed to treat Ebola virus disease and Marburg disease but was ineffective for these viral infections.
Early studies demonstrated Remdesivir's antiviral activity against several RNA viruses including SARS coronavirus and MERS related coronavirus. As of 2020, Remdesiir is being studied as a possible treatment for COVID-19, including WHO Solidarity Trial underway in over 100 countries.

How does Remdesivir work?
Remdesivir is a prodrug that metabolizes into its active form GS-441524 . This adenosine nucleoside analogue interfers with the action of viral RNA dependent RNA polymerase. It evades proof reading by viral exoribonucleases. This causes a decrease in viral RNA production and hence viral replication.
This drug is given through intravenous route. It is administrated daily for about 10 days.

What evidence is there that Remdesivir works?
Preliminary results on 29th April from a trial by the National Institutes for Allergy and Infectious disease showed patients who received the drug recovered 31% more quickly in 11 days compared with 15 for those who did not take it.
The death rate was also lower, 8% compared with 11%, but this was not statistically significant.
Before this trial, there were also positive signs from a New England Journal of Medicine paper based on data collected from patients taking Remdseivir on a compassionate basis.
In addition a leak of recording of a clinical trials investigator from University of Chicago, said the drug helped most of its patients recover and be discharged.

What is the evidence Remdesivir does not work?
Remdesivir had been described by the WHO as the biggest HOPE of treating coronavirus. However, these hopes appear to be dashed after the agency prematurely posted research which found the drug was ineffective and even potentially harmful.
A randomized double blind placebo controlled multicentric trial conducted 10 hospitals in Hubei, China published on 29th April, 2020 showed disappointing results.
237 patients were enrolled the trial showed no statistically significant benefit for those taking Remdesivir. Patients taking the drug recovered on average in 21 days compared with 23 days for those on a placebo.
Although not statistically significant, patients receiving Remdesivir had a numerically faster time to clinical improvement with symptoms of 10 days or less.

What are the problems with the trials?
Trial must enroll enough patients to be considered statistically significant. The trial conducted by National Institutes for Allergy and Infectious Diseases enrolled more than 1000 patients across the world. The above Chinese study included 237 patients but it fell short of its bigger target because China contained its outbreak, so there were not enough patients to study.
Most of the studies did not have a control arm or were, like the one described in the Journal of Medicine paper, based on data that was not collected as part of trial.
Gilead published results from its own study on Wednesday, 29th April which did not have control group. It compared people who took the drug for 5 days with those who took it for 10 days, making it hard to draw broader conclusions.

What is the position of Remdesivir drug in the competition with other drugs for the treatment of coronavirus infection?
Many other potential treatments are being investigated. Some of the drugs being tested are low priced generics such as the antimalarial hydroxychloroquine.
But, analyst had high hopes for Remdesivir based on how it has been used against Ebola and other coronavirus.

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