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Let's review the history of Remdesivir
1) Jan-Feb - COVID hits the world - remdesivir is an interesting compound that needs a home - gilead releases drug to a small number of individuals, compiles the data, and creates a historical control showing benefit https://www.nejm.org/doi/full/10.1056/NEJMoa2007016
1) Jan-Feb - COVID hits the world - remdesivir is an interesting compound that needs a home - gilead releases drug to a small number of individuals, compiles the data, and creates a historical control showing benefit https://www.nejm.org/doi/full/10.1056/NEJMoa2007016
2) April 29 - A group in Wuhan releases one of the first COVID clinical trials - on remdesivir. Small numbers but no real benefit (? reduction in time to clinical improvement) - couldn't power study appropriately given improvement in situation in Wuhan https://bit.ly/31dDASv
3) On the same day - Gilead releases a press release suggesting a significant benefit to the drug in a trial of 5 vs. 10 days - with no real control even though it's a phase III. Timing is literally hours before the release of the Wuhan study. https://www.gilead.com/news-and-press/press-room/press-releases/2020/4/gilead-announces-results-from-phase-3-trial-of-investigational-antiviral-remdesivir-in-patients-with-severe-covid-19
4) SAME day - the NIH releases the DSMB report showing the preliminary review shows ACTT-1 decreases time to recovery by 31% (11 vs. 15 days). Fauci makes a statement in the oval office that is captured by the world - saying this is the standard of care.
5) ACTT-1 Preliminary review published in May (interestingly not easy to find online) - definitely a signal towards mortality in non ventilated patients - lots of debate re: mortality and subgroup analysis, is time to recovery a useful endpoint on ordinal scale.
6) EUA authorization for Remdesivir goes through - the USA goes through a mad scramble to get drug. Other countries approve. Meanwhile a number of other "studies" of remdesivir come out sponsored by Gilead of little significance. World waits for ACTT-1 final for > 100 days
7) October - Trump takes remdesivir - and dominates the news. Meanwhile the data is slowly released on http://clinicaltrials.gov and eventually in the NEJM. No mortality difference but an interesting signal ? underpowered. https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
8) SOLIDARITY is released in preprint - and shows no benefit despite a 5x larger data set. Gilead argues open label and systemic issues with trial setup (Pot meet kettle).
9) Meanwhile in the background, there are reports that the results from SOLIDARITY were known to gilead, and many significant purchases were completed with global bodies in the interim.
The bottom line - This was medicine by press release, and really poor commercialization of a drug with limited benefit. It's lessons that skepticism matters, and without that hard mortality benefit like Dex in RECOVERY, nothing is now the standard of care.
Again we've had a rough journey amongst a number of drugs - for which commercial, private, and physician interests have clouded scientific progress. Irony is that dex - a cheap steroid, is so far the dominant figure. We're reverting back to the snakeoil era
