Markets were very excited (briefly) this week about a study that found that Gilead Sciences helped patients with coronavirus heal a little faster.
But that was all the test found: Remdesivir, unfortunately, is not a miracle cure that will help us get out of prison tomorrow.
Even worse, as Faye Flam of Bloomberg writes, the trial was in a hurry to get fast FDA approvalwithout getting useful information about which patients help or hurt the most; and now that the study is finished, we have forever lost the chance to help doctors better treat patients with the virus.
All of which raise a significant number of questions and Emergency surgeon (and professor of surgery at Wash W.) Mark Hofnagl warns “I’m sorry to say that Remdesivir is probably worth nothing …”
In an excellent topic on Twitter, Hofnagl details what he calls “some exciting drug company frauds. “
First, the likelihood before the test that an infused small molecule inhibitor of the virus would improve mortality in symptomatic patients was already quite low. Unfortunately, antiviral drugs do not work well in acute illness. This is due to their mechanism of action and host response.
Antiviral drugs usually target some aspects of virus replication / assembly / transmission. Remdesivir is a smart pharmacological prodrug that inhibits a key fragment of RNA viruses that mammals do not have. – RNA-dependent RNA polymerase and inhibits virus replication.
Unfortunately, by the time you get the symptoms of the virus, you usually already have a high / peak viral load. Thus, when you give an antiviral drug to someone who is already sick, the damage from the virus is mostly done.
He is there in large numbers and in cells.
Choose your metaphor. The cat got out of the bag. The damage is done. At this point, the host’s response to the virus is activated, and your body inhibits replication through various mechanisms (which also make you feel terrible).
So how can RDRP suppression after the fact help? The answer is probably no. This, of course, was not in this trial – there is no difference, not even a trend in mortality, but in the analysis of subgroups the duration of the disease with early / mild illness can be reduced.
Now critics of stupid drugs that should never have been accumulated by governments say, “It sounds like Tamiflu!”
Yes. This is the same as Tamiflu, which can also shorten the flu for the day, but otherwise it is a practically useless antiviral agent (and actually harmful with a poor side effect profile).
Fortunately, the side effects of remdesivir in this trial did not seem serious only 3 times more patients stop than placebo, some rashes, nothing threatens life.
Where do the Shenanigans come from?
Well, remember how maybe this Chinese study showed a shortened course in a subgroup of patients? How is Tamiflu? But hasn’t mortality changed?
A month ago, the NIAID study changed its endpoints to remove death and instead look at the duration of the dz.
They changed their destination in the middle of the race to match the only positive result of another test, that they (or at least Gilead) certainly had a copy of the document as soon as it was transferred to Lancet.
Shenanigans! Get the broom!
Since the NIH trial of Remdesivir in the news …
– Walid Gellad, MD MPH (@walidgellad) April 29, 2020
It’s like announcing a race, and then when you realize that you won’t win, declaring your destination was actually where you are standing at the moment.
Then, even more suspiciously, on the day this study comes out, Lancet, Gilead and the NIAID announced a “positive trial” and they “significantly reduced the course of the disease.” It is noteworthy that the mortality allowance did not reach the value.
By the end of the day, reports that the FDA is about to urgently approve remdesivir for treatment of COVID.
Gilead gets what he wants. No one wants to be in control in further trials, and they will argue that all future trials should not be inferior.
Before we get the answer, is this drug really changing one’s destiny, it will become the gold standard of therapy. We will probably now never know whether (unlikely probability) mortality will change.
Absolute genius. You must greet them. On the day they report a negative test of their drug, based on the press release they took for the news cycle, and with some mid-level changes at their endpoints, their now “positive” test gets their FDA approval and the test stopped.
This is an infusion, once symptomatic, you need admission, examination, etc. Indeed, even the symptoms are probably too late for such therapy to work. Prevention (as in Gvilead Truvada / PreP) would be better – but not feasible in its current form.
In any case, a big win for Gilead, but I am not impressed by any, if the evidence presented so far that this will change the rules of the game.
* * *
How long before a Hoofnagle is banned on Twitter?
Hoofnagle is not alone in his skepticism.
Yves Smith Exclaims Naked Capitalism, it is troubling to watch the public try to convince remdesivir as the only promising drug for treating coronavirusand points to new study who found and tested 47 old drugs that could treat coronavirus: the results show promising results and a completely new way to combat COVID-19