Yeah . . . JDB must've just misspelled "hydroxychloroquine" in the OP.
Remdesivir showing early promise in Chicago study
- Thread starter JamieDimonsBalls
- Start date
good summary:
https://blogs.sciencemag.org/pipeli...hats-happening-with-remdesivir#comment-316805
What’s Happening With Remdesivir?
By Derek Lowe
17 April, 2020
Well, everyone was just dealing with the news that Gilead’s antiviral remdesivir had had two trials suspended in China, when Stat‘s Adam Feuerstein and Matthew Herper broke news last night about a trial here in the US.
125 patients had been recruited at the University of Chicago to receive daily doses of remdesivir, and the only reason we have news of what’s going on is because of a series of mistakes. A Chicago infectious disease specialist overseeing the trial there mentioned during a video chat with colleagues that most of these patients had been discharged, with only two fatalities. The video was recorded and then leaked to Stat. And let’s be honest about this part: this was a severe breach of the trial protocol, the sort of thing that under other circumstances could lead to the whole thing being invalidated and not accepted by the FDA as evidence. That’s not going to happen here; everyone is just going to roll their eyes, kick their desks, and find a way to deal. But this is not the way to handle trial data – it complicates everything at a time when we don’t need to be doing that. The Chicago trial supervisor should have known better than to discuss results like this to a crowd of people over video, and whoever leaked it should have known better than to do it. Let’s not have any more of this.
Should Stat have published? That’s a classic journalism question: this was certainly news, and journalists report news. It seems certain that if they had declined that the video would have been sent to any number of other news outlets; the cat was already exiting the bag. Someone was going to run with this story, and overall I’m glad that this got sent to Feuerstein and Herper rather than to Sean Hannity or Dr. Oz. I don’t like this leak at all, but the parts I like the least are the steps that happened before the news got published.
But now that it’s out there, let’s talk about what’s in the leak. Gilead stock jumped like a spawning salmon in after-market trading on this, and one of the reasons was that that 113 of the 125 patients were classed as having “severe disease”. People ran with the idea that these must have been people on ventilators who were walking out of the hospital, but that is not the case. As AndyBiotech pointed out on Twitter, all you had to do was read the trial’s exclusion criteria: patients were not even admitted into the trial if they were on mechanical ventilation. Some will have moved on to ventilation during the trial, but we don’t know how many (the trial protocol has these in a separate group).
Note also that this trial is open-label; both doctors and patients know who is getting what, and note the really key point: there is no control arm. This is one of the trials mentioned in this post on small-molecule therapies as being the most likely to read out first, but it’s always been clear that the tradeoff for that speed is rigor. The observational paper that was published on remdesivir in the NEJM had no controls either, of course, and that made it hard to interpret. Scratch that, it made it impossible to interpret. It will likely be the same with this trial – the comparison is between a five-day course of remdesivir and a ten-day course, and the primary endpoint is the odds ratio for improvement between the two groups.
So we will have the choice to like remdesivir or to love it; there will be no direct standard of comparison for how these patients will have done without it. Everyone will be trying to synthesize such a comparator from other clinical trials and reports, but that’s a dangerous business. I hope that we can learn something from the subgroup analyses, but there’s a limit.
Bottom line: I’m sounding like a defective parrot here because I say this so often, but we have to wait for controlled trials in order to say anything definite. Such trials are underway, with actual comparisons to standard of care, but they take longer. Fast trials are generally not very interpretable, interpretable trials are generally not fast. I will be glad to see these numbers when they appear, but don’t believe anyone who runs with a “Cure for Covid!” headline, because it’s extremely unlikely that remdesivir (a single agent with a broad mechanisms that’s not optimized for this virus) is any such thing. Remember, there are as yet no single-small-molecule antiviral cures for anything, coronavirus or not. My hope for the drug is that it is effective enough to get people out of the hospitals more quickly and to keep more of them off ventilators than if they were not taking it. For that hope to be realized, we need that comparison to the people who are not taking it. This trial doesn’t have it.
https://blogs.sciencemag.org/pipeli...hats-happening-with-remdesivir#comment-316805
What’s Happening With Remdesivir?
By Derek Lowe
17 April, 2020
Well, everyone was just dealing with the news that Gilead’s antiviral remdesivir had had two trials suspended in China, when Stat‘s Adam Feuerstein and Matthew Herper broke news last night about a trial here in the US.
125 patients had been recruited at the University of Chicago to receive daily doses of remdesivir, and the only reason we have news of what’s going on is because of a series of mistakes. A Chicago infectious disease specialist overseeing the trial there mentioned during a video chat with colleagues that most of these patients had been discharged, with only two fatalities. The video was recorded and then leaked to Stat. And let’s be honest about this part: this was a severe breach of the trial protocol, the sort of thing that under other circumstances could lead to the whole thing being invalidated and not accepted by the FDA as evidence. That’s not going to happen here; everyone is just going to roll their eyes, kick their desks, and find a way to deal. But this is not the way to handle trial data – it complicates everything at a time when we don’t need to be doing that. The Chicago trial supervisor should have known better than to discuss results like this to a crowd of people over video, and whoever leaked it should have known better than to do it. Let’s not have any more of this.
Should Stat have published? That’s a classic journalism question: this was certainly news, and journalists report news. It seems certain that if they had declined that the video would have been sent to any number of other news outlets; the cat was already exiting the bag. Someone was going to run with this story, and overall I’m glad that this got sent to Feuerstein and Herper rather than to Sean Hannity or Dr. Oz. I don’t like this leak at all, but the parts I like the least are the steps that happened before the news got published.
But now that it’s out there, let’s talk about what’s in the leak. Gilead stock jumped like a spawning salmon in after-market trading on this, and one of the reasons was that that 113 of the 125 patients were classed as having “severe disease”. People ran with the idea that these must have been people on ventilators who were walking out of the hospital, but that is not the case. As AndyBiotech pointed out on Twitter, all you had to do was read the trial’s exclusion criteria: patients were not even admitted into the trial if they were on mechanical ventilation. Some will have moved on to ventilation during the trial, but we don’t know how many (the trial protocol has these in a separate group).
Note also that this trial is open-label; both doctors and patients know who is getting what, and note the really key point: there is no control arm. This is one of the trials mentioned in this post on small-molecule therapies as being the most likely to read out first, but it’s always been clear that the tradeoff for that speed is rigor. The observational paper that was published on remdesivir in the NEJM had no controls either, of course, and that made it hard to interpret. Scratch that, it made it impossible to interpret. It will likely be the same with this trial – the comparison is between a five-day course of remdesivir and a ten-day course, and the primary endpoint is the odds ratio for improvement between the two groups.
So we will have the choice to like remdesivir or to love it; there will be no direct standard of comparison for how these patients will have done without it. Everyone will be trying to synthesize such a comparator from other clinical trials and reports, but that’s a dangerous business. I hope that we can learn something from the subgroup analyses, but there’s a limit.
Bottom line: I’m sounding like a defective parrot here because I say this so often, but we have to wait for controlled trials in order to say anything definite. Such trials are underway, with actual comparisons to standard of care, but they take longer. Fast trials are generally not very interpretable, interpretable trials are generally not fast. I will be glad to see these numbers when they appear, but don’t believe anyone who runs with a “Cure for Covid!” headline, because it’s extremely unlikely that remdesivir (a single agent with a broad mechanisms that’s not optimized for this virus) is any such thing. Remember, there are as yet no single-small-molecule antiviral cures for anything, coronavirus or not. My hope for the drug is that it is effective enough to get people out of the hospitals more quickly and to keep more of them off ventilators than if they were not taking it. For that hope to be realized, we need that comparison to the people who are not taking it. This trial doesn’t have it.
As we've learned, ventilators are causing more harm than benefit for a large number of patients since they are designed for ARDS, not COVID.
https://www.statnews.com/2020/04/21/coronavirus-analysis-recommends-less-reliance-on-ventilators/
By using ventilators more sparingly on Covid-19 patients, physicians could reduce the more-than-50% death rate for those put on the machines, according to an analysis published Tuesday in the American Journal of Tropical Medicine and Hygiene
Gilead's coronavirus drug flops in first trial - FT
https://news.trust.org/item/20200423162137-vgafb
https://news.trust.org/item/20200423162137-vgafb
That isn't good news, obviously, though many other studies are ongoing.
Remdesivir targets viral replication machinery very specifically, so there is rationale for why it SHOULD work, whereas many other treatments would work by yet-unclear mechanisms. But the results will decide, not the expectation of what makes sense, at first.
Remdesivir targets viral replication machinery very specifically, so there is rationale for why it SHOULD work, whereas many other treatments would work by yet-unclear mechanisms. But the results will decide, not the expectation of what makes sense, at first.
News should be coming, but experts warn the results could be murky
https://www.statnews.com/2020/04/27...-worry-next-studies-may-increase-uncertainty/
https://www.statnews.com/2020/04/27...-worry-next-studies-may-increase-uncertainty/
we already have data on what percent are dying once we hit this or that stage of development.
let that data base be the control group.
a "time is no object" mindset doesn't work here. DUH!
seems like every time i see an interview on tv with some "expert" there to discuss how well this or that drug or combination of drugs is performing, the guest gives a 5 min lecture on all the things they don't know yet.
stop wasting wasting my time telling me what you don't know.
tell me exactly what you do know to date, what percent are responding well and what percent have died, and what are the responding well and dying percentages for those for that stage of illness who took other drugs or treatments.
no one fighting for their life in a limited time race is interested in being in the placebo group, so fk the placebo group thing and do away with it.
this isn't an academic or intellectual exercise.
how is this drug or combination or treatment doing to date vs everything else being tried.
"everything else being tried" is the placebo group.
the day one treatment is doing noticeably better than others, shift to that.
and hospitals need to be communicating with each other all the time on how well this or that, is or isn't doing.
i've heard that this isn't happening, and if not, fix that sht now, regardless of what financial or disclosure arrangement X hospital has with Y pharma company.
Wondering about buying the stock? Have cash reserve waiting to put in market. Already missed a couple companies because I was afraid to pull trigger couple weeks ago.
No, that's what controlled clinical trials MUST be, actually, in order to establish a statistical benefit and tolerable risks.
"Compassionate use" is different, though, and data from compassionate use is going to be murky and open to interpretation, because treatment course is left up to doctors rather than to following a defined clinical protocol.
How "controlled" must the control group be, though? It seems we are awash in data about COVID patients. Doesn't this open the door to constructing a control cohort based on similar clinical characteristics from patients outside the trial? Wouldn't it be a significant finding if a drug reduces death rates (statistically significant) across 2 clinically matched populations?
It wouldn't meet the criteria for FDA approval, but right now I think the goal is getting emergency use authorization, which is a lower standard.
Not trying to challenge you, just a question because you seem to be knowledgeable about clinical trials.
i'm not interested in if a treatment option does 2-3% better than those getting no treatment at all..
i'm interested in how current and new treatments are doing vs all other treatment options tried to date, and vs those who got "no treatment" to date.
you act like we don't already have a significant sample size of different treatments, or no treatment at all population, to compare against.
if we're trying to protect data on how other treatments are doing as "proprietary", then that needs to stop now.
that said, you're welcome to volunteer to take nothing if you have to go to the hospital due to the virus, to be part of the control group.
i want whatever has been working best to date vs everything else, and vs nothing at all, up to that point.
if asked to try something new, i want to get the something new, not a placebo to duplicate an already existing "no treatment" sample population, which is a waste of everyone's time and resources.
comparing treatment options of all hospitals to date gives us a "control group" to compare new treatment options against.
and again, if hospitals aren't sharing all the data they have to protect proprietary data, that needs to stop.
we're not looking for 2% gains in a 20 yr old mature trial market here, we're looking for significant jumps in effectiveness in an emerging trail market, and everyone is on the clock.
And this is why anything coming out from China should be ignored.
https://www.cnbc.com/2020/04/29/gil...ata-on-remdesivir-coronavirus-drug-trial.html
And yet the losers in the WHO continue to republish the garbage out of that country
Reading that article closely doesn't make me think this is any kind of sure fire treatment. At most, it sounds like the drug isn't harmful.
Looks like good news. Though I don't really understand what to conclude from this.
The study tracked two groups of patients who were hospitalized with Covid-19. One group received a 5-day treatment of remdesivir, while the other group took the drug for 10 days. The researchers said more than half of the patients in both treatment groups were discharged from the hospital within 14 days. They said 64.5% of the patients who received the shorter treatment course were discharged, compared with 53.8% of the group who were treated for 10 days.
The real question is whether a patient is less likely to need a ventilator or die with remdesivir, not whether a 5-day treatment is better or worse than a 10-day treatment.
A
anon_mlxxvlbug9dpa
Guest
This is not fully correct. Dosing matters. If five days of dosing is optimal over ten from a burden on hospitals perspective, cost perspective, and general pharmacology perspective (where the goal is always lowest necessary therapeutic dose), it matters.
Of course you’re right that the big question is pharmacological interventions over standard of care.
some contradictory news, indications of positive results with remdesivir
https://www.local10.com/business/20...-proved-effective-against-virus-in-us-study/?
A biotech company said Wednesday its experimental drug has proved effective against the new coronavirus in a major U.S. government study that put it to a strict test.
Gilead Sciences’s remdesivir would be the first treatment to pass such a test against the virus, which has killed more than 218,000 people since it emerged late last year in China. Having a treatment could have a profound effect on the global pandemic, especially because health officials say any vaccine is likely a year or more away.
The study, run by the National Institutes of Health, tested remdesivir versus usual care in about 800 hospitalized coronavirus patients around the world. The main result is how long it takes patients to recover.
California-based Gilead gave no details on results Wednesday, but said an announcement is expected soon. NIH officials did not immediately reply to a request for comment.
https://www.local10.com/business/20...-proved-effective-against-virus-in-us-study/?
A biotech company said Wednesday its experimental drug has proved effective against the new coronavirus in a major U.S. government study that put it to a strict test.
Gilead Sciences’s remdesivir would be the first treatment to pass such a test against the virus, which has killed more than 218,000 people since it emerged late last year in China. Having a treatment could have a profound effect on the global pandemic, especially because health officials say any vaccine is likely a year or more away.
The study, run by the National Institutes of Health, tested remdesivir versus usual care in about 800 hospitalized coronavirus patients around the world. The main result is how long it takes patients to recover.
California-based Gilead gave no details on results Wednesday, but said an announcement is expected soon. NIH officials did not immediately reply to a request for comment.
The problem is that people are looking for a magic bullet when it is unlikely that one exists. I'm more heartened by Dr. Fauci noting that he's heard positive things about the testing than I am about Gilead saying things went well, but the excitement needs to be tempered to something more like "the drug helps shorten recovery time" than "the drug stops the virus in its tracks" (not that you're saying either of those things.)
Here's another article:
https://www.statnews.com/2020/04/29...g-shows-patients-are-responding-to-treatment/
Sounds like NIH results are anticipated sooner than later.
WaPo is saying there will be an announcement from NIAID during the afternoon briefing from the Administration task force.
I won't be heartened much by anyone's spin, or any reactionary summation of any study.
I will be heartened by peer-reviewed publication of all of the data and an independent scientific analysis of that data, its limitations, and possible confounding variables (if any).
A
anon_mlxxvlbug9dpa
Guest
Everything I read from Gilead is very conservative and cautious, most likely for SEC reasons. Most of the cheerleading and hyping is coming elsewhere.
"The data shows that remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery," Fauci said at the White House on Wednesday. The data he referred to is from a large study of more than 1,000 patients from multiple sites around the world. Patients either received the drug, called remdesivir, or a placebo.
https://www.nbcnews.com/health/heal...remdesivir-shows-promise-large-trial-n1195171
https://www.nbcnews.com/health/heal...remdesivir-shows-promise-large-trial-n1195171
It is not going to be an easy task to ramp up production to the level needed to give millions of people what (so far) appears to have benefit in a 10-dose treatment schedule. It is not a particularly simple molecule.
https://cen.acs.org/biological-chem...bNtauzUCj_afQk-lJX4IsGbr8CM6QL36kd7FtWUrHJBUw
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Yes, this is the next question. How much is available? Likely to raise patent issues around the world as others attempt to replicate it.
Yup. I've seen those reports since I commented on the earlier report about a 5 day vs. 10 day regimen.
Don't get me wrong, I'm not claiming this isn't promising or worth pursuing, but I'm cynical by nature and tend to withhold judgment on things until there's a substantial amount of evidence in.
A
anon_mlxxvlbug9dpa
Guest
They’ll release their patent for compassionate use I would think. I’d be shocked if they don’t.
so what specifically has been done today to enable or ramp up US production to needed levels.
and elsewhere.
or like with masks and testing, are we just hoping the tooth fairy brings it.
This has always seemed the most promising treatment regimen out there in the realm of possibility.
I don't think it's likely to be any kind of clear cut solution.... but could well be something that brings mortality rates down and is a piece of the puzzle. As it is now.... seems this is only something that can be administered in the hospital setting... so only people really sick people taking it.
Which to my understanding, isn't ideal for how this drug works..... seems it would work much better very early on after infection. But no reasonable way to administer that early on... at least not now.
31% faster recovery time
not like flipping a switch or anything, but that's great if it holds up
not like flipping a switch or anything, but that's great if it holds up
Before today there was only a theory remdesivir would work, like hydroxychloroquine. So any major investment by Gilead to ramp-up production of this drug that wasn't really too useful for anything else was a gamble because many docs wouldn't use it without evidence.
After today, it's got US govt endorsement of evidence that it helps, so many more docs and patients will want to give it a try. Still a gamble if something better comes along next week. Wouldn't surprise me if they try for some kind of co-funding from governments for development.
Would have to push this through temporary clinics, urgent care, ASCs, etc. in order to provide to infected individuals much quicker. However, it should probably be limited to "at-risk" individuals if there was a plan to broadly roll this out.
A, they had info before today.
B, if under patent, all govts need to mandate they license it out to anyone and everyone with credible production abilities, and start building many more production facilities yesterday.
if whomever has the rights to it doesn't want to cheaply license out those rights to anyone and everyone with safe production abilities within 1 hour of every request, then all govts need to give the ok to everyone to start making it immediately anyway, and let the patent holder fight the govts in court later.
time to stop f'ing around with this.
It is great, but the impact on deaths appears not to be statistically significant. If that holds up, I am hoping people do not resume high risk behavior based on this drug being available.
IIUC, this is provided intravenously over a 5 or 10 day period. Can't imagine how you'd do that on an outpatient basis at scale.
Right now if you test Covid positive you're told to quarantine and it's hoped you don't crash. Perhaps those who test positive could be given this regimen as a matter of course, no matter how symptomatic you are. But then we're back to the supply and capacity concerns...
This is exactly what I've been wondering. I'm not hearing any estimates of impact on actual death rates.
