COVID-19 drugs that work

[Aurel]

I’d like to start a thread of positive success stories on COVID-19 drug treatments. Indeed, drugs that work and ventilators seem the best hope for those who are already very sick.

Many drugs are in clinical trials, but doctors also experiment based on their knowledge and common sense. Here is a nice example of success combining Hydroxychloroquine and zinc sulfate, plus an antibiotic:

https://techstartups.com/2020/03/28/dr-vladimir-zelenko-now-treated-699-coronavirus-patients-100-success-using-hydroxychloroquine-sulfate-zinc-z-pak-update/

[tdw28210]

Originally Posted by Aurel

I’d like to start a thread of positive success stories on COVID-19 drug treatments. Indeed, drugs that work and ventilators seem the best hope for those who are already very sick.

Many drugs are in clinical trials, but doctors also experiment based on their knowledge and common sense. Here is a nice example of success combining Hydroxychloroquine and zinc sulfate, plus an antibiotic:

https://techstartups.com/2020/03/28/dr-vladimir-zelenko-now-treated-699-coronavirus-patients-100-success-using-hydroxychloroquine-sulfate-zinc-z-pak-update/

Positive HCQ posts? BRACE FOR IMPACT

[Aurel]

Here is a nice overview of drug candidates:

[sammyg2]

No idea if this is legit, but it sounds promising:

Immunologist says he has a possible cure for the coronavirus
By Victor Garcia

Distributed Bio co-founder and CEO Dr. Jacob Glanville joined "Tucker Carlson Tonight" Friday to talk about his company's laboratory engineering a therapeutic antibody to combat the coronavirus.

"So what we have done is we've engineered neutralizing antibodies that go and block the virus. The coronavirus, if you were to zoom in on it, you would see a series, a ring of spikes, and it uses those spikes to invade human cells," Glanville said. "We've identified a series of super potent antibodies that block those spikes and therefore make the virus no longer infectious."


Glanville explained the power of antibodies, saying it helped during the Ebola epidemic.

"This is the thing that turned the tide against Ebola. The Ebola used to be a death sentence, about 50 percent mortality rate," Glanville said. "And then once a good antibody neutralizing solution was made, then I think 94 percent of people can walk away."

"So that transformed Ebola from a dangerous crisis to a manageable treatment," Glanville added.

The doctor also spoke about the advantages of antibodies over vaccines.

"We've also got antibodies to treat rabies. We've got antibodies to treat RSV in babies. Antibodies are used to for anti-venom. So this is extremely well-established platform technology. It has the advantage," Glanville said. "You can produce antibodies much faster than you can make a vaccine. And as I'd heard you mentioned previously on all that modeling, every day counts. We're venting an incredible amount of money out of our economy and risking lives. And so you want to have a medicine as quickly as possible."


Glanville outlined the process, hoping to go toward human trial this summer.

"Our next move is we hand this off to the U.S. military, a consortium from the Gates Foundation and some private groups. And all of them are going to test the potency of neutralization of our therapeutic. We're also working with Charles River Laboratories that runs safety and talks to make sure the stuff safe to put into people," Glanville said. "And we're going to go into a scaled up manufacturer. So at that point, what you do as you do a phase one last two human trial, and that's we're aiming to do that towards the end of the summer around August."

[Aurel]

There is more and more evidence that HCQ + ZPAK or HCQ + ZPAK + Zn works.

French study
Wuhan study
Dr. Zelenko
Dr. Smith

Large scale testing done in NY (1100 patients)
Novartis is testing it.

https://www.foxnews.com/media/dr-stephen-smith-on-effectiveness-of-hydroxychloroquine-with-coronavirus-symptoms-beginning-of-the-end-of-the-pandemic

[Aurel]

Here is another good success story about HCQ. In this case, the Dr. combined it with Doxycycline because z-pak may have cardiac side effects dangerous in older patients.

https://nypost.com/2020/04/04/long-island-doctor-tries-new-hydroxychloroquine-for-covid-19-patients/

[pmax]

Shows that existing antivirals probably have an effect on the Wuhan flu virus, cocktails are next.

Two-Thirds of Severe Covid-19 Cases Improved on Gilead Drug

Over 18 days, 68% of the patients improved, with 17 of the 30 patients on mechanical ventilation being able to get off the breathing device. Almost half of the patients studied were ultimately discharged, while 13% died.

Mortality was highest among those who were on a ventilator, with 18% of them dying.

...
Remdesivir, a broad-spectrum antiviral, is viewed by researchers and doctors as one of the most promising agents against Covid-19 to enter human trials to date. In lab studies conducted prior to the Covid-19 outbreak on numerous compounds, researchers at the University of North Carolina and Vanderbilt University found the drug had potent activity against against a wide variety of coronaviruses similar to the new coronavirus.

https://www.bloomberg.com/news/articles/2020-04-10/two-thirds-of-severe-covid-19-improved-on-gilead-s-remdesivir

[Aurel]

More Good news from Gilead sciences:

https://www.statnews.com/2020/04/16/early-peek-at-data-on-gilead-coronavirus-drug-suggests-patients-are-responding-to-treatment/

[pmax]

Originally Posted by Aurel

More Good news from Gilead sciences:

https://www.statnews.com/2020/04/16/early-peek-at-data-on-gilead-coronavirus-drug-suggests-patients-are-responding-to-treatment/

Sounds like good news given the apparent anecdotal cause and effect response within hours or days, just like HCQ ...

but I can't help noticing the contrast between the two as reported from the same site.

Early peek at data on Gilead coronavirus drug suggests patients are responding to treatment
By Adam Feuerstein and Matthew Herper

“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” said Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies for the hospital.
...
Asked about the data, Eric Topol, director of the Scripps Research Translational Institute, described them as “encouraging.”
...
But some of the anecdotes are dramatic. ... “Remdesivir was a miracle,” he said.

Doctors ‘keep an open mind’ about unproven coronavirus drug, but worry it could do more harm than good
By Allison Bond

April 10, 2020
“It is our duty to make sure what we are doing is evidence- and not fear-based,” said Rachel Bystritsky,

“We have to be careful to be guided by the best data we have, and to not lead people astray,” said Aruna Subramanian

“We have a tiny amount of information from looking at a small number of patients, but that information is mixed and from studies that aren’t of very good quality,” she said.

https://www.statnews.com/2020/04/10/doctors-worry-unproven-coronavirus-drug-hydroxychloroquine-harm/

It's really unfortunate that politics is so pervasive in the "scientific community".

[Aurel]

Remedsivir was patented by the Wuhan Institute of Virology for COVID-19, by the same bat lady who made the bat chimera virus with gain-of-function for human transmission. I can link all the documents if anyone is curious...

[jyl]

In this patient set, Remedsivir is being used on patients who have "severe" disease but are NOT on ventilation, so not the most severe cases. If you want some context, I have been watching data for my state (Oregon) and the ratio of death to hospitalization is about 15%, meaning if your Covid case is serious enough that you are hospitalized, you still have 85% chance of recovering. If you are hospitalized and not on a ventilator, your chances of recovery are probably even better, maybe 90+%?

So what you'd want to see from this non-placebo-controlled data isn't that "most" of 125 patients (113 with severe disease) have recovered and only a couple have died - that might not be too different from what is happening anyway. You'd want to see that patients given Remedsivir improved much faster, avoided lung damage, etc.

This data is more interesting than the HCQ data so far, because that HCQ data is in mild or very mild cases, and the HCQ placebo controlled trials aren't showing any efficacy - but there is much more and better data to come. But do note this is the "best" observational data we've seen for Remedsivir, other similar data has shown lower % of patients improving (like 70%).

There are actual placebo controlled randomized trials of Remedsivir ongoing. People have been trying to read the tea leaves from what has and hasn't been said about those. For example: none have been halted early for efficacy (bad), none have been halted early for safety (good), the ones under GILD's control have been upsized and had the endpoints changed (unclear but potentially not-good).

Anyway, I think there is a reasonable chance that Remedsivir has some efficacy in severe cases, and if so it would be the first drug found to have any such effect.

The issues with Remedsivir is more logistical. It is an IV drug, so has to be administered in a hospital setting, i.e. you only get the drug if you're already very sick and taking up a bed. It is in very short supply, I recall that it took GILD a month to make enough drug for the current trials, and it is not an easy drug to make.

[island911]

Remdesivir. I believe that I was first to post of that, weeks ago. - correction; a month ago. https://forums.pelicanparts.com/off-topic-discussions/1055195-question-smart-people-about-cornavirus.html

today their stock is doing well
https://www.cnbc.com/2020/04/16/sp-500-etf-jumps-2percent-after-hours-on-report-gilead-drug-showing-effectiveness-treating-coronavirus.html

[pmax]

If enough people say they get better hours after taking a drug be it HCQ or Remdesi, I'll believe the chances are good that those drugs do work for this disease.

The Wuhan flu looks like it is susceptible to common place antivirals and antiflu medications.

[jyl]

Ok, I just read through a deep dive on remedsivir and the ongoing trials.

Takeaways:
1. In vitro, it is potent vs SARS-COV-2 and the trial dosing is about as high as is safe, because adverse effects show up at higher doses
2. A few scattered individual patients treated with the drug had so-so results
3. About 17 Diamond Princess patients were treated with the drug in Japan, with seemingly good results, these were severe cases in older persons; no real data available
4. Some small “trials” in China yielded poor results, but turns out those did not use actual GILD-supplied drug, it was made by others (see manufacturing discussion below) so pretty meaningless
5. First real trial to read out will be a large Chinese trial (400+ patients planned). This trial is taking longer to complete than hoped, mostly because currently there aren’t as many severe cases in China as expected. An interim analysis was done at around 200 patients, trial was not stopped, means drug efficacy at the interim was not great but not nil (to put it colloquially). Suggests the topline data from complete trial could look so-so. However, the important thing (which will get missed in the initial reaction) is if there are subgroups in which the drug performs very well. Hope is that in patients who started therapy early, the drug will be clearly effective (antivirals often need to be given early to work well). Yes this trial is using genuine GILD drug.
6. Another large and well designed trial should read out in May, this is the NIAD trial. Not much info has leaked on this one.
7. The trial that got attention today is GILD’s own trial. This one does not have a placebo arm, but GILD likely has good visibility into data and that’s no doubt why they are doing an open label trial.
8. GILD is ramping up manufacturing capacity, likely based on what they are seeing from their own trial. This drug is very hard to make, it takes a year from start to end. GILD had only enough for 140K patients and that is all being committed to clinical trials and compassionate use. They have managed to cut manufacturing time to six months, by end 2020 they hope to have enough drug for 1MM patients.
9. And it is an IV drug, as mentioned before.

Basically, looks to me like this drug has a reasonable chance of being effective in at least a subcategory of patients, and it will be in short supply, so it will (should) be limited to those patients who fit the profile for efficacy.

It is unlikely to be a huge moneymaker for GILD. They can’t set a monster price for it (not in this time and political climate), 1MM commercial courses x $10K is $10BN, and frankly I’m not sure they can/will charge that much. Might well be only a few $BN revenue. Which is not a game changer for GILD, but there are big political and PR benefits too.

I bought GILD in portfolios in January for this drug (I like the stock for other things too), have not been paying super close attention to the rumours/tea leaves for the last couple months, but looks like it is time to start watching closely.

[Aurel]

GILD ~+12% pre-market opening today.

[pmax]

No surprise there isn't any mention from the Harvard types of the 25% severe side effects such as septic shock of taking remdesivir.

Originally Posted by Aurel

GILD ~+12% pre-market opening today.

Could very well be a pump and dump.

[RWebb]

Originally Posted by Aurel

I’d like to start a thread of positive success stories on COVID-19 drug treatments. Indeed, drugs that work and ventilators seem the best hope for those who are already very sick.

Many drugs are in clinical trials, but doctors also experiment based on their knowledge and common sense. Here is a nice example of success combining Hydroxychloroquine and zinc sulfate, plus an antibiotic:

https://techstartups.com/2020/03/28/dr-vladimir-zelenko-now-treated-699-coronavirus-patients-100-success-using-hydroxychloroquine-sulfate-zinc-z-pak-update/

I think it would be good to categorize drugs by their mode of action.

Some drugs may also be able to help those who are only moderately sick.

[DanielDudley]

Remdesivir seems promising, because they are only testing it on worst case patients, and it seems to be working. So far, I haven't seen any conflicting results, but it is complicated to make.

[DanielDudley]

Originally Posted by RWebb

I think it would be good to categorize drugs by their mode of action.

Some drugs may also be able to help those who are only moderately sick.

I think that shortening a moderate illness is only mildly useful. Reducing a severe life threatening episode so a person survives with few repercussions would be very useful. That's the game changer.

[jyl]

Another drug to watch is Actemra (Roche) and the similar Kevaza (sp?) (Regeneron). Worse Covid outcomes have been associated with high IL-6 levels, and older persons tend to have higher IL-6 (IL-6 is part of the immune response). These two drugs are IL-6 inhibitors normally used for rheumatoid arthritis, also used to suppress CRS (cytokine storm) in patients receiving certain immunotherapy e.g. CAR-T. You probably want a targeted immune suppressor, rather than broadly suppressing the immune system (e.g. steroids), although that is being tested too. Actemra’s patent protection is expired, which isn’t great for Roche, but realistically the biosimilars will probably have trouble ramping production so Roche will be able to make money if the drug proves effective. I think Regenron still has patent protection for its drug.