FDA authorizes 1st antiviral pill for COVID
December 22, 2021 11:18 AM Subscribe
Finally some good covid news. "In a highly anticipated decision, the Food and Drug Administration authorized the first antiviral pill to treat COVID-19 at home. The pill, called Paxlovid, is made by Pfizer. [...] The results from a Pfizer study involving more than 2,200 people at high risk for developing serious COVID-19 found Paxlovid reduced the risk of hospitalization or death by 89%, compared with a placebo, when taken within three days of first symptoms of illness. When taken within five days, the drug reduced the risk of hospitalization and death by 88%."
Also good news:
Convalescent plasma treatment for COVID-19 sees renewed promise in study
Convalescent plasma treatment for COVID-19 sees renewed promise in study
Researchers at John Hopkins University on Tuesday released the results of a 16-month nationwide study on convalescent plasma use on COVID-19 patients and found it had a 54% relative risk reduction in COVID-19-related hospitalizations.FDA clears AstraZeneca's Covid antibody treatment for immunocompromised
The AstraZeneca therapy involves getting preventive injections as often as every six months. According to a large placebo-controlled clinical trial, the cocktail is about 83 percent effective at preventing symptomatic disease during such an interval...posted by BungaDunga at 11:28 AM on December 22, 2021 [2 favorites]
AstraZeneca's scientists are testing Evusheld against the new variant, said Ruud Dobber, an executive vice president and president of the company’s BioPharmaceuticals Business Unit. They are optimistic about its efficacy against the omicron variant because both of the antibodies in the cocktail, tixagevimab and cilgavimab, target the virus’s spike protein in different and complementary ways.
I'm a pessimist and incorrigible snarker, and I'm sure there are many ways this could go horribly wrong (probably as a result of capitalism, one way or another), but this is as good as news gets.
posted by Faint of Butt at 11:29 AM on December 22, 2021 [12 favorites]
posted by Faint of Butt at 11:29 AM on December 22, 2021 [12 favorites]
Pfizer's doing good work. Nationalize them now. Void all medical patents.
posted by seanmpuckett at 11:30 AM on December 22, 2021 [39 favorites]
posted by seanmpuckett at 11:30 AM on December 22, 2021 [39 favorites]
More good news!
US Army Creates Single Vaccine Against All COVID & SARS Variants, Researchers Say
Maybe the anti vaxsers will go for this one. Have it administered by someone wearing location inappropriate camo from a matte black tacticool syringe.
posted by thatwhichfalls at 11:34 AM on December 22, 2021 [27 favorites]
US Army Creates Single Vaccine Against All COVID & SARS Variants, Researchers Say
Maybe the anti vaxsers will go for this one. Have it administered by someone wearing location inappropriate camo from a matte black tacticool syringe.
posted by thatwhichfalls at 11:34 AM on December 22, 2021 [27 favorites]
I don't mean to say that other news stories aren't as big as this one, but I'm confused why everyone I know isn't celebrating and overjoyed about this.
Like, this is a treatment is APPROVED. It will be available tomorrow. Studies are great, more vaccines are nice, but... there were 1,300 people that have died daily for the last few weeks. This should knock that down by 1/4th.
posted by bbqturtle at 11:37 AM on December 22, 2021 [18 favorites]
Like, this is a treatment is APPROVED. It will be available tomorrow. Studies are great, more vaccines are nice, but... there were 1,300 people that have died daily for the last few weeks. This should knock that down by 1/4th.
posted by bbqturtle at 11:37 AM on December 22, 2021 [18 favorites]
I'll be overjoyed when there's a plan for making sure people already have the medicine before they need it. If you have to take it within 2-3 days that might as well be you have to take it within 5 minutes. This system can't do anything within that amount of time.
posted by bleep at 11:43 AM on December 22, 2021 [9 favorites]
posted by bleep at 11:43 AM on December 22, 2021 [9 favorites]
Nationalize Pfizer?! Because our two key government health agencies, the FDA and CDC, have been such effective organizations lo these past two years?
posted by PhineasGage at 11:54 AM on December 22, 2021 [6 favorites]
posted by PhineasGage at 11:54 AM on December 22, 2021 [6 favorites]
Realistically, paxlovid is only going to be available in amounts that (globally) are going to make it very hard to get. Unless you have the money of course.
The army's Shock and Awe Warriors vaccine is only just out of phase one trials which, if I'm not mistaken, only means it's passed the "does this medicine kill people on contact?" test.
I'm considering starting a conspiracy theory about it - if they came up with this Blood and Honor! vaccine that protects from, apparently, everything perhaps they made the virus? DO THE RESEARCH!
posted by thatwhichfalls at 11:54 AM on December 22, 2021 [2 favorites]
The army's Shock and Awe Warriors vaccine is only just out of phase one trials which, if I'm not mistaken, only means it's passed the "does this medicine kill people on contact?" test.
I'm considering starting a conspiracy theory about it - if they came up with this Blood and Honor! vaccine that protects from, apparently, everything perhaps they made the virus? DO THE RESEARCH!
posted by thatwhichfalls at 11:54 AM on December 22, 2021 [2 favorites]
So, like, how is this going to play out? Are the Ivermectin people going to take this? Or are they going to refuse this because of tribal reasons?
posted by The Power Nap at 11:54 AM on December 22, 2021 [2 favorites]
posted by The Power Nap at 11:54 AM on December 22, 2021 [2 favorites]
So, like, how is this going to play out? Are the Ivermectin people going to take this? Or are they going to refuse this because of tribal reasons?
The new treatment will be declared The Mark of the Beast in 3...2...1...
posted by Billiken at 11:56 AM on December 22, 2021
The new treatment will be declared The Mark of the Beast in 3...2...1...
posted by Billiken at 11:56 AM on December 22, 2021
Cause ya’ know it only takes weeks to decide if a vaccine is effective and we will never have any more variants.
I think the point is you can pretty much plug and play whatever protein sequence you want immunity to on the surface of the nanoparticle, not that it's one and done. Same concept applies to mRNA vaccines. Plug in multiple mRNA sequences into the lipid mix and you can have multivalent vaccines.
I don't mean to say that other news stories aren't as big as this one, but I'm confused why everyone I know isn't celebrating and overjoyed about this.
Because treatment is only a stopgap at best and the job it does is already covered by the vaccine. People who are unvaccinated still have to get to the hospital early enough in their illness, be seen, get a bed, then get this course of treatment triaged to them since we only have a few hundred thousands courses of the stuff coming so availability isn't necessarily guaranteed.
posted by Your Childhood Pet Rock at 11:56 AM on December 22, 2021 [1 favorite]
I think the point is you can pretty much plug and play whatever protein sequence you want immunity to on the surface of the nanoparticle, not that it's one and done. Same concept applies to mRNA vaccines. Plug in multiple mRNA sequences into the lipid mix and you can have multivalent vaccines.
I don't mean to say that other news stories aren't as big as this one, but I'm confused why everyone I know isn't celebrating and overjoyed about this.
Because treatment is only a stopgap at best and the job it does is already covered by the vaccine. People who are unvaccinated still have to get to the hospital early enough in their illness, be seen, get a bed, then get this course of treatment triaged to them since we only have a few hundred thousands courses of the stuff coming so availability isn't necessarily guaranteed.
posted by Your Childhood Pet Rock at 11:56 AM on December 22, 2021 [1 favorite]
Cause ya’ know it only takes weeks to decide if a vaccine is effective and we will never have any more variants.
Phase one trials test safety and side effects of dosages. The situation is bad enough without us refusing to engage our brains.
And most of the anti-vaxxers will take it, because it will become their excuse not to get vaccinated. There will be a few hydro-or-bust fanatics, but most of them will be glad to have the out.
posted by praemunire at 11:59 AM on December 22, 2021 [3 favorites]
Phase one trials test safety and side effects of dosages. The situation is bad enough without us refusing to engage our brains.
And most of the anti-vaxxers will take it, because it will become their excuse not to get vaccinated. There will be a few hydro-or-bust fanatics, but most of them will be glad to have the out.
posted by praemunire at 11:59 AM on December 22, 2021 [3 favorites]
Like, this is a treatment is APPROVED. It will be available tomorrow.
It will be available to a very few people soon, probably not tomorrow. It will be many months before it is widely available even in rich countries and possibly years for the rest of the world.
posted by ssg at 12:00 PM on December 22, 2021 [4 favorites]
It will be available to a very few people soon, probably not tomorrow. It will be many months before it is widely available even in rich countries and possibly years for the rest of the world.
posted by ssg at 12:00 PM on December 22, 2021 [4 favorites]
Because treatment is only a stopgap at best
Huh? Paxlovid reduces hospitalization and death by ninety percent. What kind of stopgap is that? Maybe set against the alternative of a perfect vaccine that everyone can take and that works perfectly in everyone, but while we're wishing, I'd like a pony.
This is outstanding news. Not a panacea. But outstanding news, particularly for those for whom the vaccine doesn't work.
posted by praemunire at 12:01 PM on December 22, 2021 [50 favorites]
Huh? Paxlovid reduces hospitalization and death by ninety percent. What kind of stopgap is that? Maybe set against the alternative of a perfect vaccine that everyone can take and that works perfectly in everyone, but while we're wishing, I'd like a pony.
This is outstanding news. Not a panacea. But outstanding news, particularly for those for whom the vaccine doesn't work.
posted by praemunire at 12:01 PM on December 22, 2021 [50 favorites]
this is excellent and it seems to me like a good time for all of those who can to 1) vaccinate 2) boost 3) STAY HOME 4) WEAR THOSE MASKS
the more space and time we give for supplies to ramp up and the ill and foolish and vulnerable to get taken care of, the sooner we can imagine an end to this. happy holidays.
posted by supermedusa at 12:04 PM on December 22, 2021 [7 favorites]
the more space and time we give for supplies to ramp up and the ill and foolish and vulnerable to get taken care of, the sooner we can imagine an end to this. happy holidays.
posted by supermedusa at 12:04 PM on December 22, 2021 [7 favorites]
Glad as anyone to hear it's approved, because I've been seeing the "Paxlovid is still illegal" meme for awhile. Why did it take nearly two months to get FDA approval? The article's "highly anticipated" wordage implies a LOT of people thought this should have happened sooner.
posted by radagast at 12:07 PM on December 22, 2021 [1 favorite]
posted by radagast at 12:07 PM on December 22, 2021 [1 favorite]
People who are unvaccinated still have to get to the hospital early enough in their illness, be seen, get a bed, then get this course of treatment triaged to them
Paxlovid is a pill taken at home prior to the onset of serious symptoms. It does not require hospitalization.
Further, the Biden administration has already announced a plan to allow pharmacists to prescribe Paxlovid directly. The idea is that you get your free COVID test at the pharmacy, then (if you meet the criteria in terms of days since symptom onset and risk factors) the pharmacist checks the result and hands you your free course of Paxlovid.
It will be many months before it is widely available even in rich countries and possibly years for the rest of the world.
Pfizer already announced that it's licensing the patents royalty-free for distribution of the drug in 90-something countries. Far from perfect, but a good step toward equitable access.
posted by jedicus at 12:13 PM on December 22, 2021 [49 favorites]
Paxlovid is a pill taken at home prior to the onset of serious symptoms. It does not require hospitalization.
Further, the Biden administration has already announced a plan to allow pharmacists to prescribe Paxlovid directly. The idea is that you get your free COVID test at the pharmacy, then (if you meet the criteria in terms of days since symptom onset and risk factors) the pharmacist checks the result and hands you your free course of Paxlovid.
It will be many months before it is widely available even in rich countries and possibly years for the rest of the world.
Pfizer already announced that it's licensing the patents royalty-free for distribution of the drug in 90-something countries. Far from perfect, but a good step toward equitable access.
posted by jedicus at 12:13 PM on December 22, 2021 [49 favorites]
This is indeed good news but if you think the death cultists are gonna embrace this because it's good medicine, I think you are mistaken. The only reason the cultists will embrace this is if their death cult leaders instruct them to embrace it.
posted by glonous keming at 12:24 PM on December 22, 2021 [3 favorites]
posted by glonous keming at 12:24 PM on December 22, 2021 [3 favorites]
it seems to me like a good time for all of those who can to 1) vaccinate 2) boost 3) STAY HOME 4) WEAR THOSE MASKS
I'm a bit worried that there will now be a group of unvaxxed mask deniers that will proclaim they don't need to do any of this because the cure-all pill is now available, even if the actual delivery of a pill to their hands is months away.
posted by JoeZydeco at 12:25 PM on December 22, 2021 [4 favorites]
I'm a bit worried that there will now be a group of unvaxxed mask deniers that will proclaim they don't need to do any of this because the cure-all pill is now available, even if the actual delivery of a pill to their hands is months away.
posted by JoeZydeco at 12:25 PM on December 22, 2021 [4 favorites]
💊 MERRY CHRISTMAS 💊
posted by Gerald Bostock at 12:27 PM on December 22, 2021 [8 favorites]
posted by Gerald Bostock at 12:27 PM on December 22, 2021 [8 favorites]
The idea is that you get your free COVID test at the pharmacy
I really hope that means they're expanding access to free tests again, because at least a few months ago, my experience was that in many (almost all?) states, if you don't have insurance, finding a free PCR test is extremely hard. Only a very few places in the major cities I checked offered them at all, only one of the options had any availability within less than 3 days, and many of them required me to fill out lengthy online forms and surveys before they'd let me schedule. If you're highly motivated and tech-literate, with time to spare and a means to get around -- and good English -- then you can jump through all the hurdles. Otherwise?
posted by trig at 12:29 PM on December 22, 2021 [5 favorites]
I really hope that means they're expanding access to free tests again, because at least a few months ago, my experience was that in many (almost all?) states, if you don't have insurance, finding a free PCR test is extremely hard. Only a very few places in the major cities I checked offered them at all, only one of the options had any availability within less than 3 days, and many of them required me to fill out lengthy online forms and surveys before they'd let me schedule. If you're highly motivated and tech-literate, with time to spare and a means to get around -- and good English -- then you can jump through all the hurdles. Otherwise?
posted by trig at 12:29 PM on December 22, 2021 [5 favorites]
I think a lot of the ivermectin crowd will take it. I do think there's something just extra scary/bad/unnatural-feeling about vaccination to a lot of people, whereas "get sick, take a pill" is something they understand and don't hate. Sure there will be "Pfizer evil" types too, but I think a lot of the "vaccine hesitant" are not into immunization but completely on board with a pill series to treat covid once you contract it.
I wish they would just get vaccinated but if this keeps them out of the hospital, I call it better than nothing. Great news.
Anyone see what ages it's approved for? Is this something we could use on 0-5 kids still waiting on vaccination?
posted by potrzebie at 12:43 PM on December 22, 2021 [6 favorites]
I wish they would just get vaccinated but if this keeps them out of the hospital, I call it better than nothing. Great news.
Anyone see what ages it's approved for? Is this something we could use on 0-5 kids still waiting on vaccination?
posted by potrzebie at 12:43 PM on December 22, 2021 [6 favorites]
Aren't single medication antivirals and antibiotics susceptible to resistance? I thought these things in general should be taken with several different medicines and that's the medical best practice. I don't know if that applies to the Pfizer pill but I know on TWiV they've talked about resistance if/when certain treatments are used improperly.
posted by polymodus at 12:49 PM on December 22, 2021 [2 favorites]
posted by polymodus at 12:49 PM on December 22, 2021 [2 favorites]
I think a lot of the ivermectin crowd will take it. I do think there's something just extra scary/bad/unnatural-feeling about vaccination to a lot of people, whereas "get sick, take a pill" is something they understand and don't hate.
The only downside of this is that it's >$500 for a course of treatment, but presumably that will be covered by insurance. If a person is willing to take ivermectin / hydroxychloroquine for covid treatment, they would probably be fine with this new medication.
Unless the whole "they rushed it through trials" drama starts to happen again...
posted by theorique at 12:50 PM on December 22, 2021 [1 favorite]
The only downside of this is that it's >$500 for a course of treatment, but presumably that will be covered by insurance. If a person is willing to take ivermectin / hydroxychloroquine for covid treatment, they would probably be fine with this new medication.
Unless the whole "they rushed it through trials" drama starts to happen again...
posted by theorique at 12:50 PM on December 22, 2021 [1 favorite]
after their human trials worked so well it was unethical to not give the pill to the control group. The FDA took two months to make a decision on it.
Operation, "meh, whatever" speed?
posted by pwnguin at 12:56 PM on December 22, 2021 [4 favorites]
Operation, "meh, whatever" speed?
posted by pwnguin at 12:56 PM on December 22, 2021 [4 favorites]
The anti-vaxxers will absolutely take it. They've have had no problem taking monoclonal antibodies (*mabs), which are now running low, cost a lot more money, and are less effective than Omicron.
Everyone's brave until they're starving of oxygen and they realize death is a possibility.
posted by meowzilla at 12:58 PM on December 22, 2021 [7 favorites]
Everyone's brave until they're starving of oxygen and they realize death is a possibility.
posted by meowzilla at 12:58 PM on December 22, 2021 [7 favorites]
I think the unvaccinated will take it. Once they actually have COVID, they seem to want everything medical science has to offer (with the possible exception of those who use their dying breath to say that whatever they've got, it's DEFINITELY NOT COVID BECAUSE COVID IS A HOAX).
I'm not sure how this will play out with this drug, but as an immunocompromised person in active chemotherapy, I get irritated when scarce resources become even scarcer because a bunch of people who didn't get vaccinated need treatment.
But lately, I've been in a seething white hot COVID rage, so I'll try to calm down and be glad for a bit. Yes, this is good news.
posted by FencingGal at 12:58 PM on December 22, 2021 [16 favorites]
I'm not sure how this will play out with this drug, but as an immunocompromised person in active chemotherapy, I get irritated when scarce resources become even scarcer because a bunch of people who didn't get vaccinated need treatment.
But lately, I've been in a seething white hot COVID rage, so I'll try to calm down and be glad for a bit. Yes, this is good news.
posted by FencingGal at 12:58 PM on December 22, 2021 [16 favorites]
I get irritated when scarce resources become even scarcer because a bunch of people who didn't get vaccinated need treatment
Better they take a pill at home than tie up a bed, though, no?
posted by praemunire at 1:11 PM on December 22, 2021 [3 favorites]
Better they take a pill at home than tie up a bed, though, no?
posted by praemunire at 1:11 PM on December 22, 2021 [3 favorites]
Ah, for anyone else wondering, it's approved for age 12+.
posted by potrzebie at 1:13 PM on December 22, 2021 [6 favorites]
posted by potrzebie at 1:13 PM on December 22, 2021 [6 favorites]
When Paxlovid becomes widely available, would there be any issues with everyone who gets COVID taking it? Anecdotally, I've heard of cases where people without any known risk factors found themselves in such bad condition that they probably should've gone to the hospital, but weren't able to. Also, would it reduce severity for even mild cases, e.g. turn it into a bad cold instead of getting stuck in bed with a fever for two weeks?
posted by airmail at 1:13 PM on December 22, 2021
posted by airmail at 1:13 PM on December 22, 2021
Everyone's brave until they're starving of oxygen and they realize death is a possibility.
"There are no anti-vaxers in ICU beds"
posted by pwnguin at 1:13 PM on December 22, 2021 [4 favorites]
"There are no anti-vaxers in ICU beds"
posted by pwnguin at 1:13 PM on December 22, 2021 [4 favorites]
Aren't single medication antivirals and antibiotics susceptible to resistance?
Pfizer tried pretty hard to induce resistance to its drug and couldn't. The drug targets a highly-conserved protease enzyme required by the virus to reproduce, and although it's not impossible for it to be mutated in a way that would resist Paxlovid, it's much harder than, e.g., spike protein mutations.
posted by jedicus at 1:14 PM on December 22, 2021 [6 favorites]
Pfizer tried pretty hard to induce resistance to its drug and couldn't. The drug targets a highly-conserved protease enzyme required by the virus to reproduce, and although it's not impossible for it to be mutated in a way that would resist Paxlovid, it's much harder than, e.g., spike protein mutations.
posted by jedicus at 1:14 PM on December 22, 2021 [6 favorites]
So just after some Googling it looks like the longer term issue is how to minimize resistance. The federal approval the Pfizer pill is based on only testing it as a monotherapy but one long run concern that scientists are interested in is how to enforce its use with other medicines (e.g. Paxlovid with molnupiravir) to minimize the risk of resistance.
posted by polymodus at 1:17 PM on December 22, 2021 [1 favorite]
posted by polymodus at 1:17 PM on December 22, 2021 [1 favorite]
Also, the pill contains two antiviral drugs, a new one and a previously existing one with different mechanisms. I presume this is to ward off resistance.
posted by sjswitzer at 1:19 PM on December 22, 2021
posted by sjswitzer at 1:19 PM on December 22, 2021
No, the second drug is just there to inhibit metabolism of the first, active drug so it stays in your system longer.
posted by jedicus at 1:20 PM on December 22, 2021 [9 favorites]
posted by jedicus at 1:20 PM on December 22, 2021 [9 favorites]
Yeah Google articles quite explicitly say Paxlovid is a monotherapy. At any rate the resistance issue also applies to the Merck pill, molnupiravir, as well. Both CEOs of both companies of course say the same thing, that because of the synthetic mechanisms they cleverly chose, that will thwart the virus. Which is reasonable to say and one can believe that, but is not empirical which is why some scientists say they want to research this aspect e.g. ideally using drug cocktails like with HIV or hepatitis C.
posted by polymodus at 1:29 PM on December 22, 2021
posted by polymodus at 1:29 PM on December 22, 2021
This is should be a valuable tool at not just avoiding harm but at preventing infection and spread. "Treatment as Prevention" was the AAAS breakthrough of the year a few years ago. That was HIV focused, but applies here too. If you knock down the viral load of a patient quickly, and exposed people take it for a week, you can stop outbreaks early.
This optimistic view applies more to low-Covid situations than this winter surge.
Aren't single medication antivirals and antibiotics susceptible to resistance? I thought these things in general should be taken with several different medicines and that's the medical best practice.
Resistance is always a concern. However, the cocktail approach to antiviral treatment is to deal with chronic infections like Hepatitis C and HIV/AIDS. In those cases you have massive diversity in the virus before you've even dosed, and (especially in HIV) reservoirs that can "try out" new mutations, and partial suppression from one drug inevitably leads to a strain that beats you.
In a chronic case, you drop the viral load early and your body finishes cleaning it up. For treatment you don't need a mixture. (There are some well known and generally insightful Covid observers who seem to miss this fundamental difference.)
You can absolutely still breed resistance in a population over time as they are exposed to the drug, but one drug that's this good has the potential to help for a long time. There are other promising drugs floating around in pipelines, often targeting different parts of the virus, which would be effective as well an hopefully some would be available by next winter.
posted by mark k at 1:29 PM on December 22, 2021 [3 favorites]
This optimistic view applies more to low-Covid situations than this winter surge.
Aren't single medication antivirals and antibiotics susceptible to resistance? I thought these things in general should be taken with several different medicines and that's the medical best practice.
Resistance is always a concern. However, the cocktail approach to antiviral treatment is to deal with chronic infections like Hepatitis C and HIV/AIDS. In those cases you have massive diversity in the virus before you've even dosed, and (especially in HIV) reservoirs that can "try out" new mutations, and partial suppression from one drug inevitably leads to a strain that beats you.
In a chronic case, you drop the viral load early and your body finishes cleaning it up. For treatment you don't need a mixture. (There are some well known and generally insightful Covid observers who seem to miss this fundamental difference.)
You can absolutely still breed resistance in a population over time as they are exposed to the drug, but one drug that's this good has the potential to help for a long time. There are other promising drugs floating around in pipelines, often targeting different parts of the virus, which would be effective as well an hopefully some would be available by next winter.
posted by mark k at 1:29 PM on December 22, 2021 [3 favorites]
An interesting dive into the mechanisms of action of Paxlovid with the popular medical YouTube educator Dr Campbell. (This video is from a few weeks back but most likely not very much has changed with any of the fundamentals.)
posted by theorique at 1:35 PM on December 22, 2021
posted by theorique at 1:35 PM on December 22, 2021
There are some well known and generally insightful Covid observers who seem to miss this fundamental difference
But I don't think the heuristic of chronic vs non chronic is a black and white one because flu drugs can be resisted and flu is not a chronic infection compared to hepatitis or even h. pylori.
And like you say later, the implied issue is population level resistance. If drugs are used around the world then that's how viruses adapt to new medications. As Pfizer and Merck representatives say that likelihood seems low because of the way these new genetic drugs, Paxlovid and molnupiravir, are engineered. But at this point that is (reasonable) speculation, whereas the empirical data will come when people start using these drugs.
posted by polymodus at 1:39 PM on December 22, 2021
But I don't think the heuristic of chronic vs non chronic is a black and white one because flu drugs can be resisted and flu is not a chronic infection compared to hepatitis or even h. pylori.
And like you say later, the implied issue is population level resistance. If drugs are used around the world then that's how viruses adapt to new medications. As Pfizer and Merck representatives say that likelihood seems low because of the way these new genetic drugs, Paxlovid and molnupiravir, are engineered. But at this point that is (reasonable) speculation, whereas the empirical data will come when people start using these drugs.
posted by polymodus at 1:39 PM on December 22, 2021
For folks who think 2 months is too long, I’m going to go through the little I know about biological drug licensing (only partially applicable since this is a chemical drug).
So, you have a drug that cells crap out like yeast make ethanol. Great! Validate that those cells aren’t crapping out a weird virus that was inadvertently introduced by workers or is suddenly being expressed after hiding in the genome for years/decades. There’s probably better ways of doing this than electron microscopy but that’s the one I know of. This validation report will be ~200 pages if my own work is any indication.
Now presumably while the Upstream process development crew has been fighting the battle above and whatever other battles also exist and are codified by CFR or convention at the FDA, your downstream group is developing a purification procedure. This is my jam. Lots of separations via affinity, hydrophilic exchange, ion exchange, and combinations of the above.
BUT. Because the FDA is paranoid about Mystery Virus Expression you’re gonna need more than that. You’ll need a viral inactivation step for the maybe-existing viruses and likely a virus reduction filtration step. And if you’re using a cell line like CHO that might poop out empty XMuLV-like (xenotrophic murine lukemia virus) particles the FDA is SUPER CONCERNED. You need to prove that other viruses have no greater than a 1 in a million chance of a live viral particle (one) being in a vial of drug product. For XMuLV, it’s one in a million chance of one in a million vials (10^14) IIRC (21CFRp58 is what governs us).
The validation studies for this start at ~200 pages for very short re-validation of an existing procedure. We completed one this year that looked like a full set of the encyclopedia brittanica.
Then you have validation that the drug product is appropriately pure. Validation of the sanitization and cleaning procedures. Validation of the facility cleaning procedures and contamination prevention (hey Emergent). Validation of the sterility of packaging. Validation of stability. Validation of validation probably, I don’t know. This doesn’t even include the clinical trials!
This is an unbelievably large amount of paperwork and that someone could do even a cursory review in two months would be a heroic task. Given the high profile, I would imagine that many many people all spent two months agonizing over thousands upon thousands of pages of dense results and procedural descriptions, looking for flaws that could allow for human harm.
They likely do that anyway (I don’t know I’m not working for a regulator, don’t want that stress) but I imagine this one got even more extra attention.
posted by Slackermagee at 1:45 PM on December 22, 2021 [38 favorites]
So, you have a drug that cells crap out like yeast make ethanol. Great! Validate that those cells aren’t crapping out a weird virus that was inadvertently introduced by workers or is suddenly being expressed after hiding in the genome for years/decades. There’s probably better ways of doing this than electron microscopy but that’s the one I know of. This validation report will be ~200 pages if my own work is any indication.
Now presumably while the Upstream process development crew has been fighting the battle above and whatever other battles also exist and are codified by CFR or convention at the FDA, your downstream group is developing a purification procedure. This is my jam. Lots of separations via affinity, hydrophilic exchange, ion exchange, and combinations of the above.
BUT. Because the FDA is paranoid about Mystery Virus Expression you’re gonna need more than that. You’ll need a viral inactivation step for the maybe-existing viruses and likely a virus reduction filtration step. And if you’re using a cell line like CHO that might poop out empty XMuLV-like (xenotrophic murine lukemia virus) particles the FDA is SUPER CONCERNED. You need to prove that other viruses have no greater than a 1 in a million chance of a live viral particle (one) being in a vial of drug product. For XMuLV, it’s one in a million chance of one in a million vials (10^14) IIRC (21CFRp58 is what governs us).
The validation studies for this start at ~200 pages for very short re-validation of an existing procedure. We completed one this year that looked like a full set of the encyclopedia brittanica.
Then you have validation that the drug product is appropriately pure. Validation of the sanitization and cleaning procedures. Validation of the facility cleaning procedures and contamination prevention (hey Emergent). Validation of the sterility of packaging. Validation of stability. Validation of validation probably, I don’t know. This doesn’t even include the clinical trials!
This is an unbelievably large amount of paperwork and that someone could do even a cursory review in two months would be a heroic task. Given the high profile, I would imagine that many many people all spent two months agonizing over thousands upon thousands of pages of dense results and procedural descriptions, looking for flaws that could allow for human harm.
They likely do that anyway (I don’t know I’m not working for a regulator, don’t want that stress) but I imagine this one got even more extra attention.
posted by Slackermagee at 1:45 PM on December 22, 2021 [38 favorites]
Came here to...
posted by JoeXIII007 at 1:45 PM on December 22, 2021 [3 favorites]
echo "This is good news."posted by JoeXIII007 at 1:45 PM on December 22, 2021 [3 favorites]
But I don't think the heuristic of chronic vs non chronic is a black and white one because flu drugs can be resisted and flu is not a chronic infection compared to hepatitis or even h. pylori.
You can have resistance in a chronic disease, as I said. My point is you don't need a cocktail to treat flu. Either the strain is resistant or not. (I'm simplifying a bit, but this basically stands.)
Even with chronic infections the barrier to shutting them down early--before they become chronic--is much lower. It's why you can have effective HIV prevention without the full three-drug combo that you use for treatment of an infected person.
posted by mark k at 1:47 PM on December 22, 2021
You can have resistance in a chronic disease, as I said. My point is you don't need a cocktail to treat flu. Either the strain is resistant or not. (I'm simplifying a bit, but this basically stands.)
Even with chronic infections the barrier to shutting them down early--before they become chronic--is much lower. It's why you can have effective HIV prevention without the full three-drug combo that you use for treatment of an infected person.
posted by mark k at 1:47 PM on December 22, 2021
Sorry, not to abuse the edit window:
As Pfizer and Merck representatives say that likelihood seems low because of the way these new genetic drugs, Paxlovid and molnupiravir, are engineered.
These aren't "genetic" drugs. They are classic small molecule drugs. They both target active sites of proteins, which may increase the barrier for resistance relative to the antibody drugs (which target the virus' surface). But the main point is to hit the virus hard and stop replication so it can't sample resistant strains.
I would actually not be optimistic about Merck avoiding resistance. I haven't looked at detailed data but it isn't very effective (30% reduction, vs. 90% for Pfizer). Partially effective drugs are actually a classic way to breed resistant virus.
posted by mark k at 1:53 PM on December 22, 2021 [2 favorites]
As Pfizer and Merck representatives say that likelihood seems low because of the way these new genetic drugs, Paxlovid and molnupiravir, are engineered.
These aren't "genetic" drugs. They are classic small molecule drugs. They both target active sites of proteins, which may increase the barrier for resistance relative to the antibody drugs (which target the virus' surface). But the main point is to hit the virus hard and stop replication so it can't sample resistant strains.
I would actually not be optimistic about Merck avoiding resistance. I haven't looked at detailed data but it isn't very effective (30% reduction, vs. 90% for Pfizer). Partially effective drugs are actually a classic way to breed resistant virus.
posted by mark k at 1:53 PM on December 22, 2021 [2 favorites]
Also, mulnopiravir actually works by preventing coronavirus reproduction by causing mutations. In theory, it induces sufficient mutations to prevent replication entirely almost all the time. But many have pointed out the risk of introducing a drug that causes a whole lot of mutations, because it only takes one case where there are only a small number of mutations, that turn out to be helpful to the virus, which is then passed on to others...
It seems very unwise for us to be taking this risk for a drug that isn't even particularly effective, when a better alternative was approved at the same time. I sure hope these concerns are unfounded, but this seems like a roll of the dice that we really don't need to take.
posted by ssg at 2:04 PM on December 22, 2021
It seems very unwise for us to be taking this risk for a drug that isn't even particularly effective, when a better alternative was approved at the same time. I sure hope these concerns are unfounded, but this seems like a roll of the dice that we really don't need to take.
posted by ssg at 2:04 PM on December 22, 2021
Thank you for that explanation slackermagee. I was about to comment that 2 months seems like a very short time to approval to me, given that it's a highly technical exercise that has to be carefully carried out by a limited number of specialists. But your explanation is much more detailed and clear.
posted by roolya_boolya at 2:05 PM on December 22, 2021 [3 favorites]
posted by roolya_boolya at 2:05 PM on December 22, 2021 [3 favorites]
Another thank you for the details on validation, slagermagee.
posted by rrrrrrrrrt at 2:17 PM on December 22, 2021
posted by rrrrrrrrrt at 2:17 PM on December 22, 2021
Also good news is this preprint study from South Africa showing an 80% lower chance of hospitalization with Omicron compared to other variants. The UK study from a few days ago (PDF) was sometimes cast as saying there was no difference between Delta and Omicron hospitalization, but it really said they couldn't tell if there was a difference. If Omicron confers good immunity to other variants, it will push them out pretty effectively (the CDC estimates 70% Omicron now), so if it is less severe and Paxlovid becomes widely available this will be a much less scary disease.
On the other hand, Omicron seems wildly infective. There's some concerning case rate increases, for example New York City is reporting twice their previous highest case rate (though it was probably higher in early 2020 before testing became common). Even if Omicron is much milder, it looks like a hard winter.
posted by netowl at 2:22 PM on December 22, 2021
On the other hand, Omicron seems wildly infective. There's some concerning case rate increases, for example New York City is reporting twice their previous highest case rate (though it was probably higher in early 2020 before testing became common). Even if Omicron is much milder, it looks like a hard winter.
posted by netowl at 2:22 PM on December 22, 2021
This is good news. Let's get the pills produced, distributed, and affordable.
posted by doctornemo at 2:54 PM on December 22, 2021
posted by doctornemo at 2:54 PM on December 22, 2021
Even a wave of 'mild' cases can cause of lot of disruption. I wouldn't want to be in an ICU where half the (already less than minimal) staff is at home sick in their beds. Heck, a lot of people with fever symptoms, driving their cars to go to work because they have no sick time, can cause of lot of non-covid but excess deaths.
posted by meowzilla at 2:56 PM on December 22, 2021 [2 favorites]
posted by meowzilla at 2:56 PM on December 22, 2021 [2 favorites]
Also good news is this preprint study from South Africa showing an 80% lower chance of hospitalization with Omicron compared to other variants. The UK study from a few days ago (PDF) was sometimes cast as saying there was no difference between Delta and Omicron hospitalization, but it really said they couldn't tell if there was a difference. If Omicron confers good immunity to other variants, it will push them out pretty effectively (the CDC estimates 70% Omicron now), so if it is less severe and Paxlovid becomes widely available this will be a much less scary disease.
There are new UK papers that find a pretty clear decrease in severity as well. The biggest unknown here is still how much of that is accounted for by the fact that an increased proportion of cases are likely to be reinfection or breakthrough cases, which of course both tend to be less severe.
posted by atoxyl at 2:59 PM on December 22, 2021 [3 favorites]
There are new UK papers that find a pretty clear decrease in severity as well. The biggest unknown here is still how much of that is accounted for by the fact that an increased proportion of cases are likely to be reinfection or breakthrough cases, which of course both tend to be less severe.
posted by atoxyl at 2:59 PM on December 22, 2021 [3 favorites]
> So, like, how is this going to play out? Are the Ivermectin people going to take this?
Just name the animal version "Ivirmecten" and make it widely available at veterinarians and animal supply stores.
Then let the chips fall where they may . . .
posted by flug at 3:11 PM on December 22, 2021 [2 favorites]
Just name the animal version "Ivirmecten" and make it widely available at veterinarians and animal supply stores.
Then let the chips fall where they may . . .
posted by flug at 3:11 PM on December 22, 2021 [2 favorites]
Pfizer-mectin?
posted by theorique at 3:14 PM on December 22, 2021 [4 favorites]
posted by theorique at 3:14 PM on December 22, 2021 [4 favorites]
Tuckermectin.
posted by praemunire at 3:22 PM on December 22, 2021 [1 favorite]
posted by praemunire at 3:22 PM on December 22, 2021 [1 favorite]
While two months might be fast for a regular drug approval, when 1,000 people are dying every day, I don't have a lot of confidence that the FDA worked weekends and attempted to move up meetings to grant this. After all - it's for emergency approval. After a trial shows a 90% reduction in hospitalizations/death... Can't you look at that and make a decision in 10 minutes? What negative side effect could possibly warrant a thorough review that's worth 60,000 lives? I personally can't cut the FDA any slack. If one thousand people were dying a day, I could read through an encyclopedia in two, maybe three days. Maybe I'm oversimplifying this but if there are 10 chemical engineers and 10 epidemiologists, and after 36 hours of dividing and conquering they all give a green light, then the committee meeting should be held. I think that anyone reading this today would have put this at utmost urgency above everyone else in their lives - but the people that didn't were the people that scheduled the FDA review meeting two months after this was submitted.
I'm not alone in thinking the FDA moves too slowly. Renowned psychiatrist Scott agrees:
On the FDA
On paxlovid:
posted by bbqturtle at 3:33 PM on December 22, 2021 [2 favorites]
I'm not alone in thinking the FDA moves too slowly. Renowned psychiatrist Scott agrees:
On the FDA
On paxlovid:
posted by bbqturtle at 3:33 PM on December 22, 2021 [2 favorites]
Great measured commentary (as always), by Derek Lowe ("In the Pipeline", science.org): Paxlovid holds. .
posted by bumpkin at 3:40 PM on December 22, 2021 [2 favorites]
posted by bumpkin at 3:40 PM on December 22, 2021 [2 favorites]
> "What negative side effect could possibly warrant a thorough review that's worth 60,000 lives?"
One that could kill far more than 60,000 people?
posted by kyrademon at 3:59 PM on December 22, 2021 [7 favorites]
One that could kill far more than 60,000 people?
posted by kyrademon at 3:59 PM on December 22, 2021 [7 favorites]
My brother has a PhD in biophysics and used to work in the field, and his take on the "slow" approval process is that it's not so much "does this thing work?" but "is this thing being manufactured correctly?". Looking at the original EUA application for the vaccines, for example, there are two facilities inspectors listed, along with two product reviewers out of the 14 reviewers. You've got to make sure the factories are producing the thing properly and that just takes time-they were reviewing information from every factory.
I'll also note that skimping on the manufacturing step was what killed the early CDC covid test, at least according to the FPP on that a bit ago. There were concerns about cross contamination, they were ignored in the name of speed, and then we had non functioning tests.
posted by damayanti at 4:00 PM on December 22, 2021 [17 favorites]
I'll also note that skimping on the manufacturing step was what killed the early CDC covid test, at least according to the FPP on that a bit ago. There were concerns about cross contamination, they were ignored in the name of speed, and then we had non functioning tests.
posted by damayanti at 4:00 PM on December 22, 2021 [17 favorites]
I'll also note that skimping on the manufacturing step was what killed the early CDC covid test, at least according to the FPP on that a bit ago. There were concerns about cross contamination, they were ignored in the name of speed, and then we had non functioning tests.
There was also this case of contamination at a J&J plant that was one of the factors that led to J&J being dropped in a lot of places, and another in a shipment of Moderna vaccines to Japan.
If this drug gets released and then has to be recalled shortly afterwards, or production has to be paused, that could make a lot of people decide they don't trust it at all even when it comes back on the market. It's pretty important to get it right.
posted by trig at 4:25 PM on December 22, 2021 [16 favorites]
There was also this case of contamination at a J&J plant that was one of the factors that led to J&J being dropped in a lot of places, and another in a shipment of Moderna vaccines to Japan.
If this drug gets released and then has to be recalled shortly afterwards, or production has to be paused, that could make a lot of people decide they don't trust it at all even when it comes back on the market. It's pretty important to get it right.
posted by trig at 4:25 PM on December 22, 2021 [16 favorites]
An interesting dive into the mechanisms of action of Paxlovid with the popular medical YouTube educator Dr Campbell.
That video was a hot take on why ivermectin should be used to treat covid. There’s currently no clinical data showing ivermectin is effective in treating covid.
posted by waving at 4:40 PM on December 22, 2021 [9 favorites]
That video was a hot take on why ivermectin should be used to treat covid. There’s currently no clinical data showing ivermectin is effective in treating covid.
posted by waving at 4:40 PM on December 22, 2021 [9 favorites]
While two months might be fast for a regular drug approval, when 1,000 people are dying every day, I don't have a lot of confidence that the FDA worked weekends and attempted to move up meetings to grant this. After all - it's for emergency approval. After a trial shows a 90% reduction in hospitalizations/death... Can't you look at that and make a decision in 10 minutes? What negative side effect could possibly warrant a thorough review that's worth 60,000 lives?
My brother has a PhD in biophysics and used to work in the field, and his take on the "slow" approval process is that it's not so much "does this thing work?" but "is this thing being manufactured correctly?". Looking at the original EUA application for the vaccines, for example, there are two facilities inspectors listed, along with two product reviewers out of the 14 reviewers. You've got to make sure the factories are producing the thing properly and that just takes time-they were reviewing information from every factory.
Manufacturing issues were a problem for the J&J vaccine (remember when they had to toss 60 milion doses because of a manufacturing partner screw-up?), and are part of why the Novavax COVID-19 vaccine still isn't available in the US (it only just got EU approval). Particularly for new technologies, and for companies that haven't historically made a certain kind of treatment or drug, scale-up and manufacturing can be real pitfalls - and getting them right really is important, because great clinical results are worth nothing if you can't actually reliably manufacture the drug or vaccine or treatment that yielded those great results. That's not to say the FDA's EUA process is fine, but there is more to it than just reading reported clinical trial results.
I also wonder whether the disappointing molnupiravir results (discussed on In the Pipeline) made the FDA less willing to fast-track paxlovid until they had the full set of preliminary data, not just the interim results (which had looked rather better for molnupiravir than the full dataset ended up looking). Note that Pfizer released a bunch of results on December 14th (a week ago) that weren't in the original November EUA application, and given the timing, I'd rather assume that those did feature into the FDA's decision.
It seems very unwise for us to be taking this risk for a drug that isn't even particularly effective, when a better alternative was approved at the same time. I sure hope these concerns are unfounded, but this seems like a roll of the dice that we really don't need to take.
One possible reason is that Paxlovid is co-administered with Ritonavir, which slows down human enzymes that would otherwise break down Paxlovid before it could actually have an effect on viral replication. Unfortunately, Ritonavir itself has a lot of nasty and potentially fatal drug interactions (and gets a so-called black box warning.) For patients who can't safely take paxlovid, having another option - even a less effective one - might be worth it.
posted by ASF Tod und Schwerkraft at 4:47 PM on December 22, 2021 [7 favorites]
My brother has a PhD in biophysics and used to work in the field, and his take on the "slow" approval process is that it's not so much "does this thing work?" but "is this thing being manufactured correctly?". Looking at the original EUA application for the vaccines, for example, there are two facilities inspectors listed, along with two product reviewers out of the 14 reviewers. You've got to make sure the factories are producing the thing properly and that just takes time-they were reviewing information from every factory.
Manufacturing issues were a problem for the J&J vaccine (remember when they had to toss 60 milion doses because of a manufacturing partner screw-up?), and are part of why the Novavax COVID-19 vaccine still isn't available in the US (it only just got EU approval). Particularly for new technologies, and for companies that haven't historically made a certain kind of treatment or drug, scale-up and manufacturing can be real pitfalls - and getting them right really is important, because great clinical results are worth nothing if you can't actually reliably manufacture the drug or vaccine or treatment that yielded those great results. That's not to say the FDA's EUA process is fine, but there is more to it than just reading reported clinical trial results.
I also wonder whether the disappointing molnupiravir results (discussed on In the Pipeline) made the FDA less willing to fast-track paxlovid until they had the full set of preliminary data, not just the interim results (which had looked rather better for molnupiravir than the full dataset ended up looking). Note that Pfizer released a bunch of results on December 14th (a week ago) that weren't in the original November EUA application, and given the timing, I'd rather assume that those did feature into the FDA's decision.
It seems very unwise for us to be taking this risk for a drug that isn't even particularly effective, when a better alternative was approved at the same time. I sure hope these concerns are unfounded, but this seems like a roll of the dice that we really don't need to take.
One possible reason is that Paxlovid is co-administered with Ritonavir, which slows down human enzymes that would otherwise break down Paxlovid before it could actually have an effect on viral replication. Unfortunately, Ritonavir itself has a lot of nasty and potentially fatal drug interactions (and gets a so-called black box warning.) For patients who can't safely take paxlovid, having another option - even a less effective one - might be worth it.
posted by ASF Tod und Schwerkraft at 4:47 PM on December 22, 2021 [7 favorites]
The biggest unknown here is still how much of that is accounted for by the fact that an increased proportion of cases are likely to be reinfection or breakthrough cases, which of course both tend to be less severe.
They say 20-25% less hospital admissions overall, 11% less for unvaccinated and not previously infected, but they note that the reinfections data is not very reliable and they don't give a confidence interval for that 11%, so I wouldn't put much faith in it. Either way, 11% is pretty much insignificant.
posted by ssg at 4:50 PM on December 22, 2021 [2 favorites]
They say 20-25% less hospital admissions overall, 11% less for unvaccinated and not previously infected, but they note that the reinfections data is not very reliable and they don't give a confidence interval for that 11%, so I wouldn't put much faith in it. Either way, 11% is pretty much insignificant.
posted by ssg at 4:50 PM on December 22, 2021 [2 favorites]
I see that this approval is for use with high-risk patients. Is that limitation because they want to prioritize the limited supply? Any signals of when approval might be expanded? In the meantime, would use for low-risk patients be "off-label," but at a doctor's discretion, or not permitted at all?
posted by daisyace at 4:53 PM on December 22, 2021
posted by daisyace at 4:53 PM on December 22, 2021
Either way, 11% is pretty much insignificant.
Not in the context of a maxed-out health care system. It could always be better, of course.
posted by praemunire at 5:04 PM on December 22, 2021 [1 favorite]
Not in the context of a maxed-out health care system. It could always be better, of course.
posted by praemunire at 5:04 PM on December 22, 2021 [1 favorite]
I see that this approval is for use with high-risk patients. Is that limitation because they want to prioritize the limited supply?
The study included lower-risk patients, but the rate of hospital admissions between the placebo and the drug wasn't statistically significant for them. The viral load measures were statistically significant, so there's good evidence that it works in lower-risk patients... but not the same quality of evidence. I don't know that's why they've approved it in higher-risk patients only, but it sounds like a sufficient reason to me.
posted by BungaDunga at 5:31 PM on December 22, 2021 [1 favorite]
The study included lower-risk patients, but the rate of hospital admissions between the placebo and the drug wasn't statistically significant for them. The viral load measures were statistically significant, so there's good evidence that it works in lower-risk patients... but not the same quality of evidence. I don't know that's why they've approved it in higher-risk patients only, but it sounds like a sufficient reason to me.
posted by BungaDunga at 5:31 PM on December 22, 2021 [1 favorite]
Wow, first flogging vit D to death absent any scientific consensus and now full conspiracy theory on ivermectin? Oh well, Campbell was communicated the basics in March 2020 reasonably well.
posted by joeyh at 5:42 PM on December 22, 2021 [1 favorite]
posted by joeyh at 5:42 PM on December 22, 2021 [1 favorite]
11% is fine, the problem is that people hear "it looks milder" and up their risk budget way more than 11%.
posted by away for regrooving at 5:43 PM on December 22, 2021 [3 favorites]
posted by away for regrooving at 5:43 PM on December 22, 2021 [3 favorites]
Renowned psychiatrist Scott
That’s kind of a weird way to describe the guy. “Pseudonymous psychiatrist who is known for having a lot of opinions online?”
posted by atoxyl at 6:59 PM on December 22, 2021 [3 favorites]
That’s kind of a weird way to describe the guy. “Pseudonymous psychiatrist who is known for having a lot of opinions online?”
posted by atoxyl at 6:59 PM on December 22, 2021 [3 favorites]
They say 20-25% less hospital admissions overall, 11% less for unvaccinated and not previously infected, but they note that the reinfections data is not very reliable and they don't give a confidence interval for that 11%, so I wouldn't put much faith in it. Either way, 11% is pretty much insignificant.
It would not have occurred to me as an American that the “hospitalizations” figure used here would include visits that are not overnight admissions but it does:
The extent of reduction is sensitive to the inclusion criteria used for cases and hospitalisation, being in the range 20-25% when using any attendance at hospital as the endpoint, and 40-45% when using hospitalisation lasting 1 day or longer or hospitalisations with the ECDS discharge field recorded as “admitted” as the endpoint
Using “admissions” in the sense of people formally admitted gives a 28 percent adjusted reduction.
posted by atoxyl at 7:13 PM on December 22, 2021 [1 favorite]
It would not have occurred to me as an American that the “hospitalizations” figure used here would include visits that are not overnight admissions but it does:
The extent of reduction is sensitive to the inclusion criteria used for cases and hospitalisation, being in the range 20-25% when using any attendance at hospital as the endpoint, and 40-45% when using hospitalisation lasting 1 day or longer or hospitalisations with the ECDS discharge field recorded as “admitted” as the endpoint
Using “admissions” in the sense of people formally admitted gives a 28 percent adjusted reduction.
posted by atoxyl at 7:13 PM on December 22, 2021 [1 favorite]
Not in the context of a maxed-out health care system.
At the speed Omicron cases are increasing, an 11% reduction in hospitalizations staves off whatever bad outcome you're concerned about for less than a day.
posted by ssg at 9:01 PM on December 22, 2021 [2 favorites]
At the speed Omicron cases are increasing, an 11% reduction in hospitalizations staves off whatever bad outcome you're concerned about for less than a day.
posted by ssg at 9:01 PM on December 22, 2021 [2 favorites]
Two months is great for authorization of a new drug. FDA can be criticized for all kinds of things but not this.
I would welcome any info on your experience preparing and/or reviewing a submission package like that for Paxlovid and/or other info as evidence for why it could have been reviewed faster.
Need for a drug is not evidence that it could have been deemed safe and effective faster.
posted by Tandem Affinity at 9:15 PM on December 22, 2021 [10 favorites]
I would welcome any info on your experience preparing and/or reviewing a submission package like that for Paxlovid and/or other info as evidence for why it could have been reviewed faster.
Need for a drug is not evidence that it could have been deemed safe and effective faster.
posted by Tandem Affinity at 9:15 PM on December 22, 2021 [10 favorites]
Can't you look at that and make a decision in 10 minutes? What negative side effect could possibly warrant a thorough review that's worth 60,000 lives?
Keep in mind you are NOT giving this to the sickest people. You are giving it to people with mild-to-moderate Covid who are not hospitalized. The approval specifically excludes hospitalized people. So to save 60,000 lives you are dosing millions of people who are fairly healthy.
A rare side effect, caused either by the drug itself or a manufacturing problem, could materially impact the benefits in this case. Actual review of the data is often to define labels, indications, patients, and manufacturing specifications; it's not a binary "yes, you're good, do what you want."
Also: Given that the pill is going to be supply-constrained for the next few months, the total number of people helped by it is pretty much independent of whether approval was today or late last month.
Maybe I'm oversimplifying this but if there are 10 chemical engineers and 10 epidemiologists, and after 36 hours of dividing and conquering they all give a green light, then the committee meeting should be held.
Yes, you are. This is a case of not knowing what goes into review and approval, so assuming there must not be much to it. I get that there's venting about this god-damned pandemic going on, but you might as well have no review as do a long weekend and pretend it matters.
For example, a lot of the time would be spent in back and forth between the company and the FDA, as questions are asked and Pfizer researchers, process chemists, formulators, etc., scramble to answer them. IME in a high urgency review the submitting company is often adding supplemental data as it goes, though I don't know for sure if that happened here.
I don't have a lot of confidence that the FDA worked weekends and attempted to move up meetings to grant this.
Why not? I've been in pharma 30 years, and while I don't want to overstate my experience with FDA inspections and reviews--it's stressful and I've tried to avoid being directly involved--it's nonzero and I'm positive the FDA did in fact put in long hours and prioritize schedules and move up meetings.
In fact, I'd bet money there were meetings between the FDA and Pfizer that were basically the FDA helping Pfizer figure out how to clarify important issues without needing to run new experiments and reanalyze data.
posted by mark k at 9:19 PM on December 22, 2021 [25 favorites]
Keep in mind you are NOT giving this to the sickest people. You are giving it to people with mild-to-moderate Covid who are not hospitalized. The approval specifically excludes hospitalized people. So to save 60,000 lives you are dosing millions of people who are fairly healthy.
A rare side effect, caused either by the drug itself or a manufacturing problem, could materially impact the benefits in this case. Actual review of the data is often to define labels, indications, patients, and manufacturing specifications; it's not a binary "yes, you're good, do what you want."
Also: Given that the pill is going to be supply-constrained for the next few months, the total number of people helped by it is pretty much independent of whether approval was today or late last month.
Maybe I'm oversimplifying this but if there are 10 chemical engineers and 10 epidemiologists, and after 36 hours of dividing and conquering they all give a green light, then the committee meeting should be held.
Yes, you are. This is a case of not knowing what goes into review and approval, so assuming there must not be much to it. I get that there's venting about this god-damned pandemic going on, but you might as well have no review as do a long weekend and pretend it matters.
For example, a lot of the time would be spent in back and forth between the company and the FDA, as questions are asked and Pfizer researchers, process chemists, formulators, etc., scramble to answer them. IME in a high urgency review the submitting company is often adding supplemental data as it goes, though I don't know for sure if that happened here.
I don't have a lot of confidence that the FDA worked weekends and attempted to move up meetings to grant this.
Why not? I've been in pharma 30 years, and while I don't want to overstate my experience with FDA inspections and reviews--it's stressful and I've tried to avoid being directly involved--it's nonzero and I'm positive the FDA did in fact put in long hours and prioritize schedules and move up meetings.
In fact, I'd bet money there were meetings between the FDA and Pfizer that were basically the FDA helping Pfizer figure out how to clarify important issues without needing to run new experiments and reanalyze data.
posted by mark k at 9:19 PM on December 22, 2021 [25 favorites]
Also worth noting that the Danish data showed no reduction in severity when adjusted for age and vaccination status.
posted by ssg at 9:20 PM on December 22, 2021 [7 favorites]
“It is primarily young and vaccinated people who are infected with Omicron, and when we adjust for this, we see no evidence that Omicron should result in milder disease,” said Henrik Ullum, director of the Statens Serum Institut, Denmark’s public health agency, in a press conference on Wednesday.I think people, including a lot of media and public-facing doctors and scientists, are very eager to latch on to anything that shows possible reduced severity. Unfortunately, all we have is some evidence for slightly reduced severity and some evidence for the severity being about the same. We have good evidence that vaccination and prior infection reduces severity, but that's nothing new. The general public keeps hearing less severe and probably aren't getting the nuance. I would think a lot of people are going to figure they don't need to make any changes for Omicron because it is "less severe" — and that's going to make this wave a lot worse than it would be otherwise.
posted by ssg at 9:20 PM on December 22, 2021 [7 favorites]
At the speed Omicron cases are increasing, an 11% reduction in hospitalizations staves off whatever bad outcome you're concerned about for less than a day.
OK, you're right, we're doomed, whatever might seem to be good is actually bad, etc.
posted by praemunire at 9:36 PM on December 22, 2021 [7 favorites]
OK, you're right, we're doomed, whatever might seem to be good is actually bad, etc.
posted by praemunire at 9:36 PM on December 22, 2021 [7 favorites]
I keep thinking that it's not that the virus changed, it's that we changed. Many, many people are either vaccinated or have already had COVID. It makes sense we'd see strains that cause milder infections just because most people have one form of immunity or another.
Imagine if Omicron was the first version we faced - we'd be shut down tighter than a drum. But it's one of many waves, each wave hitting a population with more and more defenses against the worse outcomes.
That's partly why it's so hard to get good numbers on Omicron, very few immune systems are a blank slate. Each population we study has some amount of immunity etc.
posted by elwoodwiles at 10:07 PM on December 22, 2021 [2 favorites]
Imagine if Omicron was the first version we faced - we'd be shut down tighter than a drum. But it's one of many waves, each wave hitting a population with more and more defenses against the worse outcomes.
That's partly why it's so hard to get good numbers on Omicron, very few immune systems are a blank slate. Each population we study has some amount of immunity etc.
posted by elwoodwiles at 10:07 PM on December 22, 2021 [2 favorites]
I'm watching today's TWiV podcast and Racaniello says "we're gonna have resistance arising within months. You heard it here. First, AIDS, HIV antiviral, AZT, within months we had resistance. One drug therapy is not good."
posted by polymodus at 12:58 AM on December 23, 2021 [1 favorite]
posted by polymodus at 12:58 AM on December 23, 2021 [1 favorite]
I keep thinking that it's not that the virus changed, it's that we changed. Many, many people are either vaccinated or have already had COVID. It makes sense we'd see strains that cause milder infections just because most people have one form of immunity or another.
Not only our immunity but also our own psychology, level of knowledge, and familiarity with the situation has changed dramatically. I remember driving to some volunteer work I was doing in March or April of 2020 during lockdown: I put on rubber gloves to pump gas (and then sanitized my hands after taking off the gloves); I wore masks outdoors while spaced >10 feet from other people. The knowledge gaps and the uncertainty of the situation led to a lot of unnecessary precautions - but we didn't know they were unnecessary at the time!
If Omicron had the first version to drop then we would likely have reacted - psychologically, emotionally, socially - to it the same way we reacted to the first wild type. We wouldn't know the difference.
posted by theorique at 3:39 AM on December 23, 2021 [1 favorite]
Not only our immunity but also our own psychology, level of knowledge, and familiarity with the situation has changed dramatically. I remember driving to some volunteer work I was doing in March or April of 2020 during lockdown: I put on rubber gloves to pump gas (and then sanitized my hands after taking off the gloves); I wore masks outdoors while spaced >10 feet from other people. The knowledge gaps and the uncertainty of the situation led to a lot of unnecessary precautions - but we didn't know they were unnecessary at the time!
If Omicron had the first version to drop then we would likely have reacted - psychologically, emotionally, socially - to it the same way we reacted to the first wild type. We wouldn't know the difference.
posted by theorique at 3:39 AM on December 23, 2021 [1 favorite]
atoxyl: ""Renowned psychiatrist Scott
That’s kind of a weird way to describe the guy. “Pseudonymous psychiatrist who is known for having a lot of opinions online?”"
He isn't pseudonymous any more, and hasn't been for a while. His name is Scott Siskind.
I don't think I'm up for arguing about his reputation.
posted by Nancy Lebovitz at 4:22 AM on December 23, 2021 [2 favorites]
That’s kind of a weird way to describe the guy. “Pseudonymous psychiatrist who is known for having a lot of opinions online?”"
He isn't pseudonymous any more, and hasn't been for a while. His name is Scott Siskind.
I don't think I'm up for arguing about his reputation.
posted by Nancy Lebovitz at 4:22 AM on December 23, 2021 [2 favorites]
The guy's reputation includes racism, eugenics, and being ignorant as fuck about public health, so it's more than relevant when we're talking about a pandemic where inequalities very much based on demographics such as race and disability are directly affecting how much suffering and death those groups have experienced and continue to experience.
posted by Glegrinof the Pig-Man at 5:14 AM on December 23, 2021 [9 favorites]
posted by Glegrinof the Pig-Man at 5:14 AM on December 23, 2021 [9 favorites]
I don't recall racism ever being a criticism of Scott. Is that just a baseless accusation? Or is mentioning racism (for or against) make it "part of your reputation"?
Seems like a weird ad hominem on a subject mostly unrelated to the topic at hand.
posted by bbqturtle at 5:49 AM on December 23, 2021
Seems like a weird ad hominem on a subject mostly unrelated to the topic at hand.
posted by bbqturtle at 5:49 AM on December 23, 2021
Here's a whole bunch of emails where he goes hard in on "human biodiversity" and other white supremacist pro-eugenics bullshit. I don't think it's an ad hominem or unrelated to point out that the guy has expressed support for the same ideas that led Nazis to kill "undesirables," many of whom died from treatable diseases.
posted by Glegrinof the Pig-Man at 6:02 AM on December 23, 2021 [3 favorites]
posted by Glegrinof the Pig-Man at 6:02 AM on December 23, 2021 [3 favorites]
The FDA has approved Merck's molnupiravir as well. As expected it comes with some restrictions: not for use by pregnant people, and all people taking it should use contraception during and for some time after the treatment, to avoid a possible but unknown risk of birth defects.
posted by jedicus at 7:49 AM on December 23, 2021
posted by jedicus at 7:49 AM on December 23, 2021
for fun and tears i took a lil dip in the pool and it looks like the leading emergent meme amongst the death cult thought-leaders (aka 4chan-level trollfarms) w.r.t. Paxlovid is that it's just a tweaked and Pfizer-patented copycat of ivermectin. will check back with them in a few hours to see if they've decided that means it's good or it's bad.
posted by glonous keming at 8:20 AM on December 23, 2021 [7 favorites]
posted by glonous keming at 8:20 AM on December 23, 2021 [7 favorites]
Thank you for your brave service, glonous_keming.
posted by PhineasGage at 9:20 AM on December 23, 2021 [10 favorites]
posted by PhineasGage at 9:20 AM on December 23, 2021 [10 favorites]
Can't you look at that and make a decision in 10 minutes? What negative side effect could possibly warrant a thorough review that's worth 60,000 lives?
Look at it this way. We already have 30-40% of the population, depending on where you are, who are vocally against the vaccines because BIG PHARMA IS TRYING TO CONTROL US ALL WITH EXPERIMENTAL DRUGS. Yes, there is a huge public interest in getting this drug into mass production ASAP, if it works as described. But there is also a huge public interest in making the process as bulletproof as possible, no hiccups, no screwups, as little unexpected as possible, for the simple purpose of maintaining confidence in the drug and in the medical process and supply chain in general.
The drug is only useful if people will agree to take it, at the proper time and via the proper method to obtain and take it. And since this is an antiviral of the most-effective-at-the-very-beginning-of-symptoms type, it is imperative that people trust the process and seek medical attention rapidly and without hesitation.
posted by delfin at 9:34 AM on December 23, 2021 [10 favorites]
Look at it this way. We already have 30-40% of the population, depending on where you are, who are vocally against the vaccines because BIG PHARMA IS TRYING TO CONTROL US ALL WITH EXPERIMENTAL DRUGS. Yes, there is a huge public interest in getting this drug into mass production ASAP, if it works as described. But there is also a huge public interest in making the process as bulletproof as possible, no hiccups, no screwups, as little unexpected as possible, for the simple purpose of maintaining confidence in the drug and in the medical process and supply chain in general.
The drug is only useful if people will agree to take it, at the proper time and via the proper method to obtain and take it. And since this is an antiviral of the most-effective-at-the-very-beginning-of-symptoms type, it is imperative that people trust the process and seek medical attention rapidly and without hesitation.
posted by delfin at 9:34 AM on December 23, 2021 [10 favorites]
w.r.t. Paxlovid is that it's just a tweaked and Pfizer-patented copycat of ivermectin. will check back with them in a few hours to see if they've decided that means it's good or it's bad.
For their own sakes, I hope it's the former. I am beyond frustrated with these people, but enough have died.
posted by praemunire at 11:18 AM on December 23, 2021
For their own sakes, I hope it's the former. I am beyond frustrated with these people, but enough have died.
posted by praemunire at 11:18 AM on December 23, 2021
It probably means they'll decide they can save money by continuing to take the ivermectin instead of the expensive treatment, right?
posted by subdee at 11:33 AM on December 23, 2021 [1 favorite]
posted by subdee at 11:33 AM on December 23, 2021 [1 favorite]
I don't have a lot of confidence that the FDA worked weekends and attempted to move up meetings to grant this. After all - it's for emergency approval
Because the FDA doesn't have anything else on it's plate, right? Regulatory shit is HARD. I'm not saying there isn't ways to make the system better or that everything always gets the right priority from an outsiders perspective. How many OTHER treatments/vaccines/tests/whatever are in the same pipeline RIGHT NOW for emergency approval.
posted by Dr. Twist at 11:38 AM on December 23, 2021 [3 favorites]
Because the FDA doesn't have anything else on it's plate, right? Regulatory shit is HARD. I'm not saying there isn't ways to make the system better or that everything always gets the right priority from an outsiders perspective. How many OTHER treatments/vaccines/tests/whatever are in the same pipeline RIGHT NOW for emergency approval.
posted by Dr. Twist at 11:38 AM on December 23, 2021 [3 favorites]
It's pretty clear that Pfizer has been producing Paxlovid as fast as they can for some time and ramping up manufacturing capacity as rapidly as possible. They already had orders for millions of courses. But there still will be far more demand than there is supply and it will be rationed to those at highest risk (in rich countries).
So if the FDA would have approved it a little bit faster, that wouldn't have changed anything overall. Sure, maybe a very small number of people would have gotten it earlier, but then others wouldn't have had any later. The main constraint here is not the FDA.
posted by ssg at 12:02 PM on December 23, 2021 [3 favorites]
So if the FDA would have approved it a little bit faster, that wouldn't have changed anything overall. Sure, maybe a very small number of people would have gotten it earlier, but then others wouldn't have had any later. The main constraint here is not the FDA.
posted by ssg at 12:02 PM on December 23, 2021 [3 favorites]
More on why it is so hard to ramp up production of Paxlovid.
posted by PhineasGage at 12:14 PM on December 23, 2021 [2 favorites]
posted by PhineasGage at 12:14 PM on December 23, 2021 [2 favorites]
This approval is significant not because molnupiravir is an especially good drug, but because it is a rather ineffective and dangerous one. In particular, molnupiravir might create new variants of SARS-CoV-2 that evade immunity and prolong the pandemic.posted by ssg at 9:27 AM on December 24, 2021
More on why it is so hard to ramp up production of Paxlovid.
Remdesivir had the same problem. Synthesis of that thing is a fucking nightmare.
posted by Your Childhood Pet Rock at 9:48 AM on December 24, 2021 [1 favorite]
Remdesivir had the same problem. Synthesis of that thing is a fucking nightmare.
posted by Your Childhood Pet Rock at 9:48 AM on December 24, 2021 [1 favorite]
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This thread has been archived and is closed to new comments
The benefit of this 5 pill series is it can be prescribed to people at high risk of hospitalization 2-3 days after exposure/symptoms. They can take this pill from home, greatly reducing the amount of inpatient care at hospitals, and lowering their rates of severe covid by 89% (in the study). It works whether you are vaccinated or not, and is available to both groups by prescription.
There are worries we won't be able to produce enough of it soon enough, but this is the second major tool that will help end the pandemic.
posted by bbqturtle at 11:22 AM on December 22, 2021 [40 favorites]