[HN Gopher] Antiviral Molnupiravir Reduces Risk of Hospitalizati...
___________________________________________________________________
Antiviral Molnupiravir Reduces Risk of Hospitalization/Death by ~50
Percent
Author : _Microft
Score : 166 points
Date : 2021-10-01 15:45 UTC (7 hours ago)
(HTM) web link (www.merck.com)
(TXT) w3m dump (www.merck.com)
| nikolay wrote:
| I wonder, what could be the potential drawbacks of protease
| inhibitors taken for long periods for prophylaxis? Aren't some
| essential processes going to be negatively and unpredictably
| affected?
| DominikPeters wrote:
| I enjoyed this article explaining in more detail how the drug
| works, though much of it goes over my head:
| https://www.nature.com/articles/s41594-021-00657-8
|
| Briefly, it causes the copying process of viral RNA to go wrong
| by increasing the number of G-to-A and C-to-U mutations. A
| potential worry is that such mutations will also increase in
| places where we don't want them, such as in host DNA, but
| apparently at least for mitochondrial RNA things look good.
| SamBam wrote:
| > A potential worry is that such mutations will also increase
| in places where we don't want them
|
| Can anyone speak to how the drug avoids this? I've tried
| reading the literature, such as the Nature link above, and have
| failed to see what makes the drug specific to the virus.
| DominikPeters wrote:
| Nature link says the drug targets RdRp specifically which is
| a type of RNA copying mechanism (mostly?) confined to
| viruses. Wikipedia says about RdRp:
|
| > RdRps can be used as drug targets for viral pathogens as
| their function is not necessary for eukaryotic survival. By
| inhibiting RNA-dependent RNA polymerase function, new RNAs
| cannot be replicated from an RNA template strand, however,
| DNA-dependent RNA polymerase will remain functional.
| AndrewBissell wrote:
| It's also known to be mutagenic in mammalian cells, see the
| link I posted in a reply to the parent.
| rossdavidh wrote:
| Well one possibility is that, like chemotherapy or radiation
| vs. cancer, it's worth the risk. The body has DNA-repair
| mechanisms that could clean up the mess, if you're only
| taking the pill for a short time. The virus does not. Just a
| guess.
| AndrewBissell wrote:
| Seems like a lot of added potential risk for anyone at low odds
| of being hospitalized for Covid.
|
| https://pesquisa.bvsalud.org/global-literature-on-novel-coro...
| roflc0ptic wrote:
| Curious why this is downvoted. Is this person wrong? It seems
| like an important detail if the drug is actually mutagenic in
| mammalian cells.
| sterlind wrote:
| It is misleading but not directly wrong. Excessively high
| doses lead to mutations, but that's true for aspartame too.
| Nothing suggests that a therapeutic dose for a short time
| will give you cancer any more than X-rays from plane travel
| (i.e. there's a causal mechanism, but it's not
| statistically significant.)
|
| See my reply to them for more details.
| sterlind wrote:
| Full text here it's not trivial to find [1].
|
| This study doesn't show that molnupiravir (rNHC) is genotoxic
| at levels effective for treating covid. Dosage of 1um reduced
| COVID+ cells by 15x, while 3um removed the infection
| entirely. [2] 1um and even 3um dosing didn't lead to any
| statistically significant genotoxicity, only 10um showed
| effects [3].
|
| The authors know this, because their conclusion is that the
| risk of genotoxicity "might not be zero." They have not
| demonstrated that therapeutic doses cause any statistically
| significant increase in mutations.
|
| 1. https://academic.oup.com/jid/article/224/3/415/6272009?log
| in...
|
| 2. https://academic.oup.com/view-
| large/figure/283696469/jiab247...
|
| 3. https://oup.silverchair-
| cdn.com/oup/backfile/Content_public/...
| cinntaile wrote:
| It clearly states that clinical use should be carefully
| considered, so don't worry they're aware of its side-effects.
| jonnycomputer wrote:
| The wikipedia article on the drug mentions worry about it being
| a mutagen with some kind of controversy. Difficult for this
| layman to evaluate.
| gfodor wrote:
| This is phenomenal news - I'm also curious how the various
| tribalist memes evolve. Will the vaccine maximalists who
| ridiculed "horse paste" when the data was still weak in part
| because a pill-based regime would undermine the message that
| vaccines ought to be mandatory embrace this much needed second
| tier therapeutic? Will the anti-vaxxers who will inevitably see
| this as the goal of a big pharma conspiracy covering up the
| efficacy of their drug of choice demonize this treatment despite
| the fact it conflicts with their fears of a vaccine conspiracy
| and will undermine the justification of mandates? Get the
| popcorn.
|
| edit: Maybe this should be marketed as Ivermectin 2? I bet that
| would get more unvaccinated people to take it.
| crooked-v wrote:
| The vaccine maximalists ridicule "horse paste" because many
| people are literally buying and ingesting products intended for
| livestock.
| micromacrofoot wrote:
| yeah I hate this line of discussion because it tries to form
| some sense of "both sides" equivalency... and I think there's
| a big difference between supporting vaccine mandates and
| literally taking horse medicine.
| barbinbrad wrote:
| In his Nobel-prize lecture, the Merck scientist William
| Campbell, talks about how Ivermectin was always intended to
| be used in humans.
|
| Two relevant quotes from his speech are, "I had always
| insisted that our written departmental objectives would
| include the development of new drugs for control of parasites
| in humans" and "The end of ivermectin is nowhere in sight."
|
| Check it out: https://www.nobelprize.org/prizes/medicine/2015
| /campbell/lec...
| crooked-v wrote:
| I'm not talking about ivermectin itself. I'm talking about
| how people are literally going to livestock supply stores,
| buying products that contain ivermectin but come in forms
| and dosages intended for livestock, and ingesting those
| (even when intended for topical usage), based entirely on
| internet advice and without any kind of doctor oversight.
|
| That's where "horse paste" mockery comes from.
| [deleted]
| hunterb123 wrote:
| Maybe they couldn't get a doctor to prescribe them the
| human pill because of all the politicization so they took
| the "horse paste" version.
|
| You seem to have first hand knowledge of all these
| people's situations, are you following people to the
| livestock supply stores or talking out of your ass from
| stories you read on Reddit?
|
| Most people that I know have that have took Ivermectin
| were taking the human pill. Only on the internet and news
| media have I seen people talking about horse paste.
|
| Also, some vet meds are okay for humans (as long as you
| dose correctly), yeah you shouldn't take them, but that
| doesn't stop some of my liberal friends I know from
| taking horse tranqs (ketamine).
| crooked-v wrote:
| It's been well-documented in the news, including people
| being hospitalized after overdosing on the stuff:
|
| https://www.mississippifreepress.org/15002/person-
| hospitaliz...
|
| https://www.usatoday.com/story/news/health/2021/08/25/ive
| rme...
|
| https://www.fda.gov/consumers/consumer-updates/why-you-
| shoul...
| [deleted]
| gfodor wrote:
| Since you cited the hilarious poison control story, you
| might enjoy this analysis:
| https://astralcodexten.substack.com/p/too-good-to-check-
| a-pl...
| hunterb123 wrote:
| At least one of those was debunked, but yeah the same
| news that said that someone was convinced to drink fish
| bowl cleaner because T recommended hydroxychloroquine
| when it turned out she was trying to poison her husband.
| It's a smear campaign and if people are taking it, it's
| because they can't get the human form. It's perfectly
| safe to take the human form and people take it
| preventively.
|
| You'd think the HN crowd would be for elective controlled
| drug consumption and against pushing people into
| black/grey markets.
|
| Kinda rich coming from the people who try to use ketamine
| (omg horse tranqs!) for everything.
| SideburnsOfDoom wrote:
| The only reason that they want an ineffective pill that
| doctors rightly won't prescribe, but not a safe and
| effective vaccine, is as you say, "politicization".
|
| It's still a bad idea, on multiple levels: taking
| Ivermectin for COVID in the first place, taking the horse
| paste version, self-administering, and guessing the dose.
| gfodor wrote:
| No, your first sentence shows you're lacking an
| understanding. They genuinely fear the vaccine and
| believe Ivermectin works. If it was exclusively about
| politics they'd embrace the vaccine since both Trump and
| Biden are pro-vaccine.
|
| Taking Ivermectin for COVID from a doctor as an
| objectively "bad idea" is ridiculous, because it has been
| widely prescribed around the world for COVID. At best, it
| is a "marginally pointless idea."
| SideburnsOfDoom wrote:
| Ivermectin is useful for control of parasites in humans (1)
| and other animals such as horses, but the grandparent is
| also correct, people are "literally buying and ingesting
| products intended for livestock" - from the veterinary
| aisle (2), and self-administering random doses not safe for
| humans, with bad consequences (3). It's sheer lunacy to do
| that. If it was effective for COVID-19 (a virus, not
| parasite), then medical staff would be administering
| correct doses.
|
| 1) https://www.who.int/tdr/news/2018/moxidectin-approved-
| as-tre...
|
| 2) https://www.iflscience.com/health-and-medicine/store-
| only-le...
|
| 3) https://www.npr.org/sections/coronavirus-live-
| updates/2021/0...
| hunterb123 wrote:
| Ivermectin is not just for control of parasites, the
| anti-viral properties it has is because it's a protease
| inhibitor. It prevents certain viruses from binding to
| cells.
|
| How effective it is at inhibiting binding is the
| question. This pill in the article and Pfizer's
| prophylactic are most likely more effective since it's
| not a by product but the intent. Also more profitable
| because of patents.
| gfodor wrote:
| Nah, not many are, it's being prescribed by doctors on the
| hope that maybe it kinda sorta works. (It probably doesn't.)
| It's a safe and widely used drug so on net it isn't a
| terrible idea if you have an extremely high risk person.
| Though my understanding is the evidence in favor has gotten
| weaker over time.
| alistairSH wrote:
| I probably fall into the "vaccine maximalist" category, having
| family who fall into high-risk categories (age, immune-
| compromised).
|
| This doesn't change my feelings. The existence of a treatment
| doesn't negate the importance of vaccination. It does make me
| hopeful that a return to normal may come sooner than later, as
| any new treatments reduce the risk of my family dying should
| they, despite their best efforts, become infected.
| alistairSH wrote:
| _The existence of a treatment doesn 't negate the importance
| of vaccination._
|
| I never would have thought that statement was controversial
| in any way. I'd say the same thing for measles too.
|
| But here we are. Humans are weird.
| gfodor wrote:
| People who are vaccine maximalists are those who hear news
| like this pill and primarily are concerned about its effect
| on vaccinations, as opposed to being happy we now have
| multiple effective defensive and offensive measures against
| the virus, which was always going to be necessary for us to
| return to normal.
| yupper32 wrote:
| Not exactly going to be the same thing.
|
| Merck is applying for EUA use of this medication for Covid-19,
| something that Ivermectin never had. In addition, further
| studies didn't show Ivermectin to be useful for Covid. The
| study that first looked at Ivermectin has been proven to be not
| useful.
|
| If another study came out opposing the Merck data, then we'd
| have to dig in as well to find out why, and see if either study
| was faulty, and if more studies are required or not.
|
| This is how science and medicine works.
|
| There is a large group of people that see disproving
| studies/claims to mean that some higher power is holding back
| the miracle cure. That's what happened with Ivermectin,
| Hydroxychloroquine, etc. This is not how science and medicine
| should be viewed.
| gfodor wrote:
| My guess is that:
|
| - anti-vaxxers will eagerly take the pill, but believe that
| Merck covered up Ivermectin's efficacy to get this drug to
| market. the claim the vaccine's EUA was held up by lack of
| evidence of such pills will be memory holed
|
| - the pro-mandate authoritarians will swallow the pill
| (figuratively, pun intended) when the powers that be
| celebrate this as a success and it begins being widely
| deployed.
|
| in other words, we all win. the failure mode is if a divisive
| political figure takes a strong position on the pill being
| safe or not safe. fortunately I don't see this happening.
| yupper32 wrote:
| I don't think it's a win that a significant portion of the
| population will only take a medication if it's wrapped in a
| conspiracy theory.
| gfodor wrote:
| Well that ship already sailed. My point about the win is
| that the memetics of a safe, effective pill imply to me
| that it will actually be widely adopted by unvaccinated
| and will also calm a lot of people down who currently are
| having a bit of a mental crisis over the existence of
| said unvaccinated people. So we should be happy for
| several reasons of this news.
| crooked-v wrote:
| This is great news, but I worry that many people are going to
| take it as a continued excuse to actively avoid vaccination.
| Halving hospitalization rates would still leave ICUs everywhere
| filled with COVID patients taking beds away from people with
| other life-threatening conditions.
| paulgdp wrote:
| Here's a nice Twitter thread explaining how this works:
|
| https://twitter.com/bert_hu_bert/status/1444018619059429377
| davidw wrote:
| A potential bottleneck in the deployment of this is that only
| Heimdall is able to wield the Molnupiravir.
| rossdavidh wrote:
| Thor! Or, perhaps, The Thing and the Hulk. Superman probably as
| well. So, still, a shortage of capable health-care workers to
| distribute, you're correct.
| EricE wrote:
| I'm sure this won't be patented and instead will be given away
| for free.
|
| Right?
| b9a2cab5 wrote:
| Considering vaccines are widely available and cheap or free,
| there's no reason this should be given away for free.
| sudosysgen wrote:
| Uhm, no they're not. Many countries are struggling to acquire
| vaccines even today as they waste away in the US.
| _Microft wrote:
| Trying to improve my skills in recognizing denialism, I would
| say that this was the "Nefarious Intent" technique, wrapped in
| a layer of sarcasm?
|
| https://doctorow.medium.com/a-denialism-taxonomy-eeb1a276684...
| guyzero wrote:
| I'm excited to hear why the EUA for this drug is good when anti-
| vaxers have said they didn't trust the EUA for the vaccines.
| r00fus wrote:
| This drug helps the anti-tax after infection, but the vaccine
| helps others and only preventatively.
|
| Also was this medication developed using "mRNA"? That "messing
| with your RNA" angle is hammered repeatedly in conservative
| circles - enough that some of my not-right-wing neighbors are
| worried about it (like, go ahead and vax, but not for the
| children!!).
| [deleted]
| throwaway64643 wrote:
| So next, if you don't agree to take this drug after getting
| COVID, you'll be excluded from getting ICU bed if needed?
| dukeofdoom wrote:
| This drug will be a big blow to those that support further
| lockdowns and plans for divided society based on vaccination
| status. The logic for coerced vaccine mandates was already on
| shaky ground. This will help to defeat it. If theres an effective
| treatment, you can't force emergency use a vaccine.
| whateveracct wrote:
| Pfizer isn't emergency use
| vixen99 wrote:
| No, that is incorrect. The FDA Only renewed emergency use
| authorization for Pfizer; Approval was for BioNTech's
| Comirnaty with additional safety studies required (until
| 2027). It's currently not available in the US.
| ceejayoz wrote:
| False.
|
| https://www.reuters.com/article/factcheck-fda-pfizer/fact-
| ch...
|
| > The FDA state that Comirnaty has the same formulation as
| the EUA-approved (Emergency Use Authorization) Pfizer
| vaccine and is interchangeable (here). Their website says:
| "Providers can use doses distributed under EUA to
| administer the vaccination series as if the doses were the
| licensed vaccine. For purposes of administration, doses
| distributed under the EUA are interchangeable with the
| licensed dose." (here).
| guilhas wrote:
| "Reuters is seeking comment on the legal specificities of
| the FDA approval and will update the check in due
| course."
|
| How convenient. Pfizer states that both vaccines are
| legally different. Meaning even with the same formula
| 'Pfizer' vaccine has no liability for compensation
| claims, 'Comirnaty' has but it is not being supplied
| ceejayoz wrote:
| "I can't be bothered to Google" and "convenient" aren't
| quite the same thing. The information you seek is readily
| available.
|
| The two have the exact same liability setup.
|
| https://www.washingtonpost.com/politics/2021/08/30/false-
| cla...
|
| > "There are no liability or compensation differences
| between a countermeasure approved under an EUA or one
| that has received full FDA approval," confirmed an HHS
| spokesperson.
|
| Pfizer also has a more specific comment on the legal
| specifics in this article:
|
| > "The statement that the products are 'legally distinct
| with certain differences' refers to the differences in
| manufacturing information included in the respective
| regulatory submissions," said Pfizer spokesperson Sharon
| J. Castillo in an email. "Specifically, while the
| products are manufactured using the same processes, they
| may have been manufactured at different sites or using
| raw materials from different approved suppliers. FDA
| closely reviews all manufacturing steps, and has found
| explicitly that the EUA and BLA [biologics license
| application] products are equivalent."
| guilhas wrote:
| "The PREP Act designation means that claims related to
| coronavirus vaccines are covered by the Countermeasures
| Injury Compensation Program (CICP), not the National
| Vaccine Injury Compensation Program (VICP), which was set
| up to handle vaccine lawsuits. ... The liability
| protections afforded under the PREP Act are tied to the
| declared public health emergency and not whether the
| vaccine is sold under an EUA"
|
| OK... because of the "state of emergency" there is
| actually no compensations for either the vaccines
|
| I feel so much safer
| spear wrote:
| It's the same thing -- Comirnaty is the brand name of the
| Pfizer/BioNTech COVID vaccine.
| dukeofdoom wrote:
| I'm not sure if that's the case legally. Is windows 11
| same as windows 10, since both are a type of windows
| released by the same company. Let's say there's a
| security feature that works the same in both versions.
| But in windows 11 it was certified to work. I don't think
| you could sue effectively it failed in your installation
| of windows 10. MS could just say you should had no
| expectation for it to work because it wasn't certified to
| work at that time when you purchased your product. In
| fact the lack of certification necessarily implies that
| you used the feature at your own risk, and take full
| liability
| TechBro8615 wrote:
| EUA or Non-EUA, who cares? These are just words. They're not
| useful for much, other than appeals to authority (or lack of
| it).
| dukeofdoom wrote:
| Last time I kept up with this, it was some purposeful legal
| loophole. The drug that got approved, is not yet available.
|
| I have a friend who is a nurse that's getting fired because
| she will not take the vaccine. She has patients that had
| adverse effects from the vaccine. I totally understand why
| she would not take it.
| ceejayoz wrote:
| > Last time I kept up with this, it was some purposeful
| legal loophole. The drug that got approved, is not yet
| available.
|
| No, that was a maliciously stupid misreading of the FDA's
| statement.
|
| https://www.reuters.com/article/factcheck-fda-pfizer/fact-
| ch...
|
| > The FDA state that Comirnaty has the same formulation as
| the EUA-approved (Emergency Use Authorization) Pfizer
| vaccine and is interchangeable (here). Their website says:
| "Providers can use doses distributed under EUA to
| administer the vaccination series as if the doses were the
| licensed vaccine. For purposes of administration, doses
| distributed under the EUA are interchangeable with the
| licensed dose." (here).
| programmarchy wrote:
| The language still seems slippery because while the
| formulation may be the same and interchangeable for
| providers, the legal process bound to the license could
| be different for the recipient. If the PREP Act still
| applies, then there's less recourse for anyone that may
| experience an adverse reaction.
| ceejayoz wrote:
| No change there. Same recourse for both.
|
| https://www.jdsupra.com/legalnews/fda-approval-of-pfizer-
| vac...
|
| > Does PREP Act liability protection extend to Comirnaty?
|
| > Yes. The government invoked the PREP Act in response to
| the COVID-19 pandemic. Under the terms of that act,
| "covered persons" are granted certain immunity from
| liability for activities related to "covered
| countermeasures." Covered persons include essentially all
| of the entities involved in the manufacture,
| distribution, and administration of the countermeasure.
| The term "covered countermeasures" includes both approved
| COVID-19 products, as well as unapproved products used
| under an EUA. The Comirnaty approval does not change the
| status of the vaccine as a covered countermeasure under
| the PREP Act, and the approved vaccine should receive
| equal liability protection compared to the version of the
| vaccine used under the EUA.
|
| https://www.washingtonpost.com/politics/2021/08/30/false-
| cla...
|
| > "The statement that the products are 'legally distinct
| with certain differences' refers to the differences in
| manufacturing information included in the respective
| regulatory submissions," said Pfizer spokesperson Sharon
| J. Castillo in an email. "Specifically, while the
| products are manufactured using the same processes, they
| may have been manufactured at different sites or using
| raw materials from different approved suppliers. FDA
| closely reviews all manufacturing steps, and has found
| explicitly that the EUA and BLA [biologics license
| application] products are equivalent."
|
| > Indeed, contrary to the claims of Malone and others,
| the Comirnaty vaccine has the same liability protection
| as the vaccine approved under the EUA. That's because of
| a law known as the Public Readiness and Emergency
| Preparedness Act (PREP Act).
|
| > "The liability protections afforded under the PREP Act
| are tied to the declared public health emergency and not
| whether the vaccine is sold under an EUA," Castillo said.
| "Therefore, both Comirnaty and the Pfizer-BioNTech
| covid-19 vaccine receive the same liability protections
| as medical countermeasures against covid-19."
| programmarchy wrote:
| Ah, even worse than I expected. I should've known. It's
| funny how they triumphantly phrase it as a good thing
| that the public should take on all of the risk, while the
| most powerful take on virtually none. Furthermore,
| there's now an enormous incentive to lobby for never
| ceasing the public health emergency, since at that point
| they'd lose their enhanced liability protection.
| tinus_hn wrote:
| But is it patented, expensive and in limited supply?
| AndrewBissell wrote:
| So an abbreviated trial in 775 people is considered sufficient to
| move forward with drug approval now?
| sudosysgen wrote:
| For a safety trial, likely not, but for an efficacy trial, this
| is pretty conclusive. In any case full approval will not be
| granted with even more in the way of trials.
| SideburnsOfDoom wrote:
| > So an abbreviated trial in 775 people is considered
| sufficient to move forward with drug approval now?
|
| No. They don't have full approval, and aren't likely to get it
| in the next few months.
|
| From the article:
|
| > Merck Plans to Seek Emergency Use Authorization in the U.S.
| as Soon as Possible
|
| Emergency Use Authorization is not full approval, and obviously
| comes with oversight and data gathering. "as soon as Possible"
| is not now. But they might get that in the next few months.
|
| Other than that, I don't know what to say about "sufficient to
| move forward" - any drug at any stage of trials is either
| abandoned or moving forward? A small trial that meets its goals
| is sufficient to move forward to the next trial so .. yes? But
| not to full approval, which they aren't getting anyway.
|
| This is an existing (but fairly new) drug so there there is
| other data on safety etc, links seem to be about 2019 onwards,
| at https://en.wikipedia.org/wiki/Molnupiravir
| AndrewBissell wrote:
| Was using "approval" colloquially, I understand the
| distinction between that and "authorized." However I have
| seen many larger trials for other repurposed drugs being
| tried in early treatment dumped on as "underpowered" so it's
| just odd that that criticism is nowhere to be found in this
| case. There were 7 people hospitalized in the trial group and
| 14 in the placebo.
| loeg wrote:
| The criticism is not present because this one wasn't
| underpowered.
|
| > p=0.0012
| [deleted]
| gus_massa wrote:
| I guess you are wondering why this is better than Ivermectin.
| From the article:
|
| > _The MOVe-OUT trial (MK-4482-002) (NCT04575597) was a global
| Phase 3, randomized, placebo-controlled, double-blind, multi-
| site study_ [...]
|
| If you go to https://ivmmeta.com/ you will see:
|
| * Most of the studies have not placebo, they just compare a
| group of people with another unrelated group of people. It's
| very difficult to be sure there are no unexpected differences.
|
| * If you filter only the RCT, most of them are not
| statistically significant. That is a problem because if the
| drug has no effect, the reporting/publishing/selection bias
| will cause barely significant studies to accumulate.
|
| * There are only 6 that RCT that are statistically significant.
| Have you read them? Some have very weird things that are very
| big red flags.
|
| If Ivermectin has no effect, I expect like 2 of the RCT that
| are statistically significant to be caused by flukes. Can you
| pick your favorite 3?
| caeril wrote:
| I think we/they have to.
|
| I'll don my tinfoil hat for a moment. A combination of initial
| vaccine effectiveness estimates having to be downgraded, and
| variants reducing effectiveness further, along with the
| infectiousness data of vaccinated carriers putting the herd
| immunity targets at risk have public health authorities
| scrambling for the next potential solution.
|
| The data out of Israel and other places is _damning_. Not in
| the sense that anti-vaxxers would like, but in the sense that
| we are still nowhere near containing this thing.
|
| We either need better vaccines, or drugs. So yes,
| epidemiological standards will relax in the face of a worldwide
| pandemic, to some extent.
| endisneigh wrote:
| Hospitalization _from COVID-19_
| mmastrac wrote:
| Funny that we just assume that anyways these days.
| javierbyte wrote:
| I had to check the title to make sure it is not there. I
| totally read "from COVID-19" in my mind.
| hncurious wrote:
| There's a joke in here about the conflation of the data all
| throughout the pandemic and how there's been a failure to
| differentiate between _with Covid_ and _from Covid_.
|
| https://www.theatlantic.com/health/archive/2021/09/covid-hos...
| loeg wrote:
| The full article title is:
|
| _Merck and Ridgeback's Investigational Oral Antiviral
| Molnupiravir Reduced the Risk of Hospitalization or Death by
| Approximately 50 Percent Compared to Placebo for Patients with
| Mild or Moderate_ COVID-19 _in Positive Interim Analysis of
| Phase 3 Study_
|
| The HN one is somewhat arbidged.
| _Microft wrote:
| If you want to read a comment on this, try Derek Lowe's:
|
| https://www.science.org/content/blog-post/molnupiravir-thor-...
|
| Wikipedia has an article on the drug already if you would like to
| have a look at that instead:
|
| https://en.wikipedia.org/wiki/Molnupiravir
| kazinator wrote:
| > _exerts its antiviral action through introduction of copying
| errors during viral RNA replication_
|
| How does this target only viral RNA, not the body's own?
|
| Copying errors don't sound like something you want in your own
| RNA.
|
| "However, there are inherent risks in this approach. NHC can be
| metabolized by the host cell to the 20-deoxyribonucleoside form
| by the ribonucleotide reductase and then incorporated into the
| host cell DNA. The mutagenic effect of NHC has been shown in
| animal cell cultures (10), raising concerns on the potential
| risk of molnupiravir-induced tumorigenesis and the emergence of
| detrimental mutations in sperm precursor cell generation and
| embryo development."
|
| https://www.jbc.org/article/S0021-9258(21)00667-0/pdf
|
| Yikes. I think, instead of quaffing carcinogens, it's wiser to
| get vaccinated.
| wk_end wrote:
| 100% agreed on getting vaccinated, but for the elderly or
| immunocompromised people vaccination isn't enough to
| necessarily prevent severe outcomes and it might be worth the
| risk. As a young person, I'd probably stay away, at least in
| the near term, given how effective vaccines are.
| kazinator wrote:
| If you're elderly, I suppose it's down to how many years
| you have left under various outcome scenarios under various
| risks.
|
| You're not going to reproduce, so reproductive harm isn't
| an issue.
| hanselot wrote:
| If the metric is lethality, they certainly are very
| effective.
| rossdavidh wrote:
| I believe the reason the trial was in unvaccinated people,
| was so that it would have a big enough signal to detect
| quickly. If you did the same trial with vaccinated subjects,
| it might still be making a 50% reduction in hospitalization,
| but it would take a lot longer to detect that. I don't think
| the idea is to only give it to the unvaccinated.
| xxpor wrote:
| I'd love to talk to someone who refused to get vaccinated
| but gave their informed consent to participate in this
| trial.
|
| Kind of boosts my personal theory is that a lot of vaccine
| hesitancy is driven by the fact that it's an injection and
| if it were a pill instead people would be more willing to
| take it.
| ashtonkem wrote:
| Your theory is entirely possible. But I'd also like to
| point out that the study population was entirely Covid
| positive people with one or more risk factors. Presumably
| if you're overweight, over 60, and have Covid you
| probably are willing to take more risks than before to
| improve your odds of not dying. Even the vaccine hesitant
| might accept that risk.
| _holographic_ wrote:
| There has never been a disease in history where the official
| guideline was to stay at home until you can't breath anymore.
| Doctors around the world who treat this virus EARLY with off
| patent drugs like ivermectin have very good results (as good as
| the ones announced here). The western world has utterly failed in
| this pandemic.
| carbocation wrote:
| I think it's disappointing that this thread has devolved into a
| political discussion that is hardly related to the topic. The
| scientific/medical achievement here seems significant.
|
| As an MD, the difference between calling in a script for a pill
| and arranging for outpatient infusion therapies is vast.
| SideburnsOfDoom wrote:
| > devolved into a political discussion
|
| Welcome to the "intelligentsia" debating anti-Covid measures.
| On the topic, you usually see worse than this.
| andybak wrote:
| Be wary of commenting on the tone of a thread. Skimming it 39
| minutes later and it seems a very reasonable, varied thread.
| Wait for voting to do it's thing.
| sudosysgen wrote:
| Indeed. The opportunity for prophylaxis with an oral antiviral
| is also amazing.
| [deleted]
| Marsymars wrote:
| I definitely would not want to be taking a mutagenic
| prophylactically.
| sudosysgen wrote:
| I was talking about post exposure prophylaxis. This drug
| does have mutation concerns.
|
| If I'm choosing between a taking the drug right now for 2-3
| days in lower doses Vs a 50% chance of taking much higher
| doses for 2 weeks, id take the former.
| freemint wrote:
| The moment you have symptoms peak replication is already
| over for two da,s. It's to late by then.
| dougmwne wrote:
| Thank you for weighing in. I am hugely excited about this and
| immediately sent a message to all my family. I know people who
| died because they didn't know that antibody treatments were
| available and effective when given early enough. I very likely
| saved my own father's life by helping him to get an antibody
| treatment when he and his own doctor knew nothing about it at
| the time. When we're talking about pre-hospitalization, this
| knowledge is everything. This pill is hugely promising and I
| will be following it closely.
| helloguillecl wrote:
| Would you mind to share which antibody treatment were you
| able to get for your father? I would be useful for the rest
| of us if we ever find ourselves in this situation again.
| dougmwne wrote:
| It was the Monoclonal antibody treatment that is part of
| the official NIH treatment recommendations. There are a few
| formulations with different brand names, but the
| recommendation is to take whatever is first available and
| there is not published evidence of one being better than
| the others. I don't even know which he was given and does
| not matter at this point. The infusion lasted several hours
| at our local hospital and required a positive Covid test
| and needed to be ordered by a doctor stating that there
| were enough comorbidities to justify the treatment, the
| went through a lottery weighed on risk factors, then an
| appointment was scheduled. It is free to the patient but
| very expensive to taxpayers. It needs to be given as soon
| as possible after symptom onset to have the greatest
| effect.
|
| The odd thing is that you have to start pushing strongly on
| the paperwork to get this fairly invasive treatment when
| you still feel perfectly well in order to get it in time.
| You have to act quickly purely on your risk factors and not
| on how you are feeling.
|
| That's why this pill has so much potential. It could be
| handed out immediately after a positive test and
| prescription and is easy enough that it becomes "why not"
| instead of "why". Of course this is a very new drug, but
| for certain high risk people it may make a ton of sense.
| EricE wrote:
| There are actually a multitude of treatments beyond waiting
| for thing to get bad enough that you need to go to the
| hospital: https://aapsonline.org/covidpatientguide/
|
| This is also worth a watch:
| https://www.youtube.com/watch?v=QAHi3lX3oGM
| dougmwne wrote:
| To anyone seeing this link please beware. The linked PDF
| recommends several treatments that have insufficient
| evidence of being safe or effective, such as Ivermectin
| and Hydroxychloroquine. The only pre-hospitalization
| treatment currently recommend by the NIH with strong
| evidence is Monoclonal antibodies. Other previously
| recommended treatments such as steroids and Remdesivir
| have weak or conflicting evidence. Steroids are still
| recommended in a hospital setting.
|
| I'm sure many of us are familiar with sources of statical
| bias and issues such as multiple testing error. These
| things apply to clinical trials just as much as email
| subject line testing. That is why it is important to
| focus care on treatments that have strong evidence and
| continuing to study new treatments with insufficient
| evidence. Politics should not determine treatment,
| evidence should.
|
| Please see the NIH pages on current covid care
| recommendations, which also include pages on treatments
| with insufficient evidence, their theorized mechanism and
| the state of research.
|
| https://www.covid19treatmentguidelines.nih.gov/management
| /cl...
| blacksqr wrote:
| Document link goes to AAPS web site.
|
| Wikipedia: "The Association of American Physicians and
| Surgeons (AAPS) is a politically conservative non-profit
| association that promotes medical disinformation, such as
| HIV/AIDS denialism, the abortion-breast cancer
| hypothesis, vaccine and autism connections, and
| homosexuality reducing life expectancy."
| dougmwne wrote:
| That's terrifying. The website looks completely legit at
| first glance and my first clue that something was off was
| the Ivermectin. I had a bunch of cognitive dissonance
| trying to figure out why this very legit association of
| doctors was publishing crap. If I had less information
| about current standard of care they would have got me.
| How putrid.
| [deleted]
| [deleted]
| admeyer wrote:
| Paragraph near the bottom of Reuters article on Molnupiravir
| states:
|
| "Merck has said data shows molnupiravir is not capable of
| inducing genetic changes in human cells, but men enrolled in its
| trials had to abstain from heterosexual intercourse or agree to
| use contraception. Women of child-bearing age in the study could
| be pregnant and also had to use birth control."
|
| Link to said Reuters article:
| https://www.reuters.com/business/healthcare-pharmaceuticals/...
|
| What do you suppose would happen?
| PaulDavisThe1st wrote:
| Read this comment (directly above this question at the time of
| reading): https://news.ycombinator.com/item?id=28722155
| TrevorJ wrote:
| I believe that is standard for trials like these.
| mmastrac wrote:
| If I understand things correctly, this only helps _before_
| hospitalization.
| dibujante wrote:
| My understanding as well. By the time people are hospitalized,
| the disease isn't necessarily still prolific in their body; the
| post-infection damage kills them.
| sudosysgen wrote:
| It is possible that it could allow for more aggressive immune
| modulation and immune suppression in people where post-
| infection and immune damage is the main issue.
| loeg wrote:
| The trial was on non-hospitalized patients, because you can't
| test impact on hospitalization risk with patients that are
| already hospitalized. But given the supposed mechanism of
| action, I don't think there's any reason to believe it would
| not also be an effective therapy for hospitalized patients.
| matt_heimer wrote:
| This drug is an antiviral and isn't the Covid viral load
| already on the decline by the time that most people are
| hospitalized? See Fig 2 from
| https://www.bmj.com/content/371/bmj.m3862 . Its the other
| issues like the inflammatory cytokine response, tissue
| damage, and secondary infections that cause the poor outcomes
| in most hospitalized patients.
|
| So you'd need to take any antiviral early on. I think they
| said within 5 days in this study. Also of interest is that
| the 5 day marker is where the mild and severe cases diverge
| according to the article I linked to.
| linuxftw wrote:
| It makes one wonder why they administer remdesivir and
| other similar drugs to hospitalized patients.
| _3u10 wrote:
| Yes, so similar to ivermectin, it doesn't work.
| loeg wrote:
| No, that seems to be false?
|
| > At the interim analysis, molnupiravir reduced the risk of
| hospitalization or death by approximately 50%
| _3u10 wrote:
| Studies indicate ivermectin works given before
| hospitalization, doesn't work during hospitalization.
| loeg wrote:
| No. Studies on ivermectin are mixed, and it seems like
| the ones that showed positive effects had falsified
| data[1]. Additionally, this trial does _not_ demonstrate
| that Molnupiravir is ineffective after hospitalization.
|
| [1]:
| https://www.theguardian.com/science/2021/jul/16/huge-
| study-s...
| twofornone wrote:
| No, _one_ of the positive studies about ivermectin had
| questionable data. There are dozens of studies with
| positive results. This post and the article you linked
| are misinformation.
|
| Edit: I don't normally comment on downvotes but the
| sentiment expressed by the silent downvoters in this
| thread is pretty gross. We're trying to have a discussion
| here, but clearly certain perspectives are not allowed,
| even if supported by data. There is nothing incorrect
| about what I posted, or what GP posted about studies
| showing that ivermectin does potentially work (these
| studies exist, are peer reviewed and published, even if
| they are _weak_ studies as claimed), yet here we all are
| sitting at -4 for daring to go against the so called
| "consensus" by citing published literature. This
| censoriousness is uncalled for, counterproductive, and,
| totally ascientific.
| _3u10 wrote:
| The Science(tm) works by consensus. Your papers are
| irrelevant, and not part of the consensus, therefore you
| are wrong, because that's how the scientific method
| works.
|
| Have you considered taking likely mutagenic drugs with no
| history of what the side effects may be that are well
| supported by The Science(tm) instead?
|
| Downvote away, I've got over 12k karma to burn, sadly you
| can only burn 4 of them.
| raphlinus wrote:
| At least two pro-ivermectin studies have been retracted.
| The remaining evidence is weak. I don't think your claim
| of misinformation is well supported.
|
| https://www.nature.com/articles/s41591-021-01535-y
| twofornone wrote:
| The misinformation lies in the implication that we know
| with certainty that ivermectin is not an effective
| prophylactic/early stage treatment. We have a large body
| of mixed results.
| gfodor wrote:
| They should just brand this drug as the "New Ivermectin",
| kill two birds with one stone and save countless lives.
| Comeon marketing people, I believe in you!
| dopamean wrote:
| Right. Other wise "reduces risk of hospitalization" wouldn't
| make sense...
| loeg wrote:
| Well, yeah -- tautologically, it only helps reduce risk of
| hospitalization before hospitalization. But it could still be
| a useful therapy post-hospitalization -- I don't know.
| felistoria wrote:
| People need to be proactive and get tested if they feel a
| sickness coming on. It seems like there are a few good
| treatments if you catch it early. When you are hooked up to a
| ventilator it is too little too late.
| TechBro8615 wrote:
| Now we need a way to get these pills safely to someone's door
| in less than 24 hours. If you call your doctor just when
| you're developing Covid symptoms, he should be able to get a
| regimen of these pills delivered to you on the same day.
| Without that, they're not only pointless but will seem
| ineffective.
| mc32 wrote:
| Will this affect mandate requirements, if as effective as it's
| claimed? If so we don't need to reach hard to achieve 95%
| vaccination rates and we can get closer to a normal life.
| gizmo686 wrote:
| No. You will never be able to get this to enough of the people
| who need it when they need it. By the time most people seek
| treatment it is too late for antivirals to be effective.
|
| Even if that wasn't the case, there us too much political
| momentum behind mandates in the US for this to change the
| course.
| opinionbanned wrote:
| Hopefully not. mandates are great and we need more forced
| Medical procedures. Maybe forced sterilization or lobotomies
| will finally return.
| mmastrac wrote:
| If it halves hospitalizations, it'll have a pretty drastic
| effect on overwhelmed ICUs but there's probably still a ways to
| go before ICU levels return to normal and we can skip mandates.
| KaiserPro wrote:
| remember that in exponential growth, halving the people going
| to hospital buys you one extra doubling time. (ie, if numbers
| increase every two weeks, halving the growth buys you two
| extra weeks.) You need to make sure that the growth has
| stopped, not just halved.
| _3u10 wrote:
| Yup, and with an R value for delta between 5 and 8 on a two
| week infection cycle... well thats about 3 days... even
| with 100% of people vaccinated it will buy about a month,
| assuming the vaccine numbers hold and 1/35th of the vaxxed
| vs unvaxxed get hospitalized.
| smnrchrds wrote:
| Alberta has 173 normal ICU beds. As of this Monday, there
| were 312 Albertans in ICUs, 265 of whom for COVID [1]. The
| extra 139 beds were surge capacity, created by shutting down
| other services, postponing surgeries, and diverting resources
| to COVID ICU treatments.
|
| Even if the number of COVID patients in ICUs halved, we would
| have 132 people in the ICU with COVID, or 179 patients in
| total for all causes. It would still be over capacity and
| need surge beds, but it would still be much better than the
| current state. What this tells me is that whether we can skip
| mandates depends a lot on healthcare capacity in your region.
| Maybe the US with its higher population-adjusted ICU beds can
| get back to normal sooner than Canada.
|
| [1] https://www.cbc.ca/news/canada/edmonton/alberta-health-
| care-...
| shrubble wrote:
| Alberta has 4.4 mln or so people.
|
| Colorado, with 5.8 mln people, has over 1700 ICU beds.
|
| Alberta's been 'running on fumes' re: ICU beds and they got
| caught out...
| PaulDavisThe1st wrote:
| Arguably, most of the world's industrial economies have
| been running on fumes increasingly over the last 30-40
| years, as "fat has been trimmed", JIT supply chains have
| taken over, and "efficiency via merger-then-closure" have
| been common themes in national economies.
| smnrchrds wrote:
| I don't think the two jurisdictions count ICU beds the
| same. Alberta (and Canada in general) have about half as
| many ICU beds per capita as the US, not 1/10th. If I had
| to guess, I would say the number for Colorado includes
| other types of ICU (neonatal, cardiac, etc.) that the
| Albertan number doesn't. Alberta has 8,513 acute care
| beds. How many of those would be counted as ICU beds per
| the Colorado definition, I don't know.
|
| https://www.albertahealthservices.ca/about/about.aspx
| logicalmonster wrote:
| What are normal ICU levels and is this a goalpost that can
| ever be achieved?
|
| Long before Covid, it was well-known that hospital ICUs were
| designed to run fairly close to 100% capacity because it
| wasn't profitable to pay for staff that weren't truly needed
| at any given time. Is there any hospital that is going to pay
| for far more staff than they need and somehow manufacture
| many ICU beds out of nowhere? I feel like this is a goalpost
| intentionally designed to never be achievable.
|
| As further evidence, if the situation was actually so dire,
| would unvaccinated people (many of whom already had Covid) be
| on the chopping block in so many locations?
| easytiger wrote:
| Not to mention standardised admission criteria and ICU
| eligibility criteria were chucked out the window in many
| countries when covid became a thing
|
| _Edit_ downvotes and no discussion. This place is getting
| worse
| crooked-v wrote:
| > and is this a goalpost that can ever be achieved?
|
| It could absolutely be achieved. Literally the only thing
| keeping things from going back to more-or-less normal
| conditions right now is that there are many unvaccinated
| people getting extremely ill from COVID and filling up
| ICUs.
| logicalmonster wrote:
| Again, what are normal ICU levels?
|
| As far as I'm aware, ICU staffing is modified to achieve
| close to 100% capacity at all times with minimal spare
| beds, whether pre-Covid or post-Covid. If this is the
| case, then there's no scenario possible, regardless of
| what happens with Covid, where hospitals report anything
| but "few ICU beds are available".
| PaulDavisThe1st wrote:
| The data collected in the US by the Department of Health
| has routinely shown ICU availability in my county (Santa
| Fe, NM). That data has generally indicated that roughly
| half the available ICU beds are filled, with 1 or 2
| patients there due to COVID.
|
| p.s. according to our local newspaper, this data is
| incorrect.
| _3u10 wrote:
| Norway, Sweden, and the UK no longer have mandates, it's a
| political question not a medical question.
| jeltz wrote:
| We, Sweden, lifted the mandate 2 days ago and after a clear
| trend of the small fourth wave not increasing.
| _3u10 wrote:
| Precisely. Also congrats on having sane politicians.
| Sweden has 10x the hospitalization rates of many
| countries that still have mandates, thus it is a
| political question, not a medical one.
| jeltz wrote:
| What countries? Show me the data.
|
| Edit: Deleting most of my post since Sweden does not
| track hospitalizations, only ICU admissions so I compared
| incorrectly. Here is the graph for ICU, judge for
| yoruselves if there are any with a 1/10 of Sweden's
| numbers.
|
| https://ourworldindata.org/grapher/weekly-icu-admissions-
| cov...
| _3u10 wrote:
| I misspoke, it was deaths, not hospitalizations. Norway
| has 1/10th the deaths per capita of Sweden. Canada has
| 1/2 of what Sweden has, and we are still have mandates
| and restrictions.
| kwhitefoot wrote:
| > it's a political question not a medical question.
|
| Not as much here in Norway as it is in the UK. Our death
| rate per unit population is one tenth of the UK and local
| authorities remain prepared to reinstate restrictions. Here
| we have been living pretty much normally for months already
| anyway.
|
| And while the government has occasionally overreacted both
| the government and population have mostly followed the
| Norwegian Public Health Institute (FHI) advice.
| dham wrote:
| > it's a political question not a medical question.
|
| >> Our death rate per unit population is one tenth of the
| UK and local authorities
|
| It's a fat question at the end of the day. Norway doesn't
| have many fat people.
| KaiserPro wrote:
| given the UK's death rate, I wouldn't use it as a data
| point for success.
| mrfusion wrote:
| If we're worried about hospital capacity why are we firing
| healthcare workers?
| loeg wrote:
| We have vaccine mandates because infected healthcare
| workers spreading COVID reduce capacity even more. We
| haven't actually fired many workers, because the vast
| majority just get the vaccine (mostly before the mandates).
| LurkingPenguin wrote:
| 1. You need to account for the fact that some percentage
| (perhaps large) of healthcare workers already survived
| COVID and have natural immunity. Since the science is
| demonstrating that natural immunity is as durable and
| robust as vaccine immunity (if not more durable and
| robust), one would have to ask what the rationale is for
| firing workers who have natural immunity (as verified by
| a past COVID diagnosis or presence of antibodies) and do
| not want to be vaccinated.
|
| 2. The science is clear that vaccinated individuals can
| contract and spread the virus. While this doesn't mean
| that the vaccines aren't useful (they absolutely are), we
| need to be realistic about this in high-risk settings.
| frostirosti wrote:
| > do not want to be vaccinated What's the reason for
| this? The vaccine has been approved fully by the FDA and
| hundreds of millions of people have received it.
|
| > 2. ... Sure, and people who have had covid and get it
| again as well. But why risk sick days, lost productivity,
| severe illness when there's an effective, safe
| alternative. The capital cost of caring people who get
| sick with covid is far higher on a per capita basis for
| those who are unvaccinated.
| LurkingPenguin wrote:
| > do not want to be vaccinated What's the reason for
| this? The vaccine has been approved fully by the FDA and
| hundreds of millions of people have received it.
|
| It's none of your business why they don't want to be
| vaccinated. If science demonstrates that COVID survivors
| have strong immunity, why should they be forced to be
| vaccinated as well? We do not force people who can show
| immunity to measles, mumps, and rubella to get the MMR
| vaccine.
|
| From the CDC:
| https://www.cdc.gov/vaccines/vpd/mmr/public/index.html
|
| > You do not need measles, mumps, and rubella (MMR)
| vaccine if you meet any of these criteria for presumptive
| evidence of immunity*:
|
| > You have laboratory confirmation of past infection or
| had blood tests that show you are immune to measles,
| mumps, and rubella.
|
| > Sure, and people who have had covid and get it again as
| well. But why risk sick days, lost productivity, severe
| illness when there's an effective, safe alternative. The
| capital cost of caring people who get sick with covid is
| far higher on a per capita basis for those who are
| unvaccinated.
|
| You are distorting the science by trying to lump people
| who survived COVID in with the unvaccinated. They are not
| the same group.
|
| From Israel: https://www.medrxiv.org/content/10.1101/2021
| .08.24.21262415v...
|
| > SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI,
| 8.08 to 21.11) increased risk for breakthrough infection
| with the Delta variant compared to those previously
| infected, when the first event (infection or vaccination)
| occurred during January and February of 2021. The
| increased risk was significant (P<0.001) for symptomatic
| disease as well. When allowing the infection to occur at
| any time before vaccination (from March 2020 to February
| 2021), evidence of waning natural immunity was
| demonstrated, though SARS-CoV-2 naive vaccinees had a
| 5.96-fold (95% CI, 4.85 to 7.33) increased risk for
| breakthrough infection and a 7.13-fold (95% CI, 5.51 to
| 9.21) increased risk for symptomatic disease. SARS-
| CoV-2-naive vaccinees were also at a greater risk for
| COVID-19-related-hospitalizations compared to those that
| were previously infected.
|
| > This study demonstrated that natural immunity confers
| longer lasting and stronger protection against infection,
| symptomatic disease and hospitalization caused by the
| Delta variant of SARS-CoV-2, compared to the BNT162b2
| two-dose vaccine-induced immunity. Individuals who were
| both previously infected with SARS-CoV-2 and given a
| single dose of the vaccine gained additional protection
| against the Delta variant.
| frostirosti wrote:
| I wonder if the answer to all of this changes if
| insurance companies decide that covering the cost of
| laboratory confirmation of covid 19 antibodies or the
| cost covering the expenses related to hospitalization
| exceed the cost of vaccination people who may not need
| it.
|
| If Aetna decided to not cover hospitalization if you are
| not vaccinated (or I'll give you laboratory confirmed
| immune), then it would be an entirely different calculus
| for people.
|
| The argument of "Oh well I'll just find a different
| insurance provider" doesn't track in the United States
| either because most people do not have that option. The
| mandate and the exchange has been almost entirely gutted,
| so you're left with the option your employer provides.
|
| That's another good point too. The government really
| doesn't have a lot of say in terms of whether or not
| you're vaccinated, it's entirely your employer. At the
| end of the day it's not Aetna/Kaiser/Blue Cross/et al.
| covering your health care costs, it's your employer. They
| certainly do not want to cover any unnecessary expense.
| So requiring employees to be vaccinated is the simplest,
| scalable, and cost effective solution.
|
| If we're going to point to organizations that have no
| tolerance for the unvaccinated for diseases other than
| covid, we need look no futher than the US military:
| https://www.hhs.gov/immunization/who-and-when/military-
| membe...
| howlong wrote:
| _The vaccine has been approved fully by the FDA and
| hundreds of millions of people have received it._
|
| Not unlike Red Bull and Cap'n Crunch.
| zdragnar wrote:
| Healthcare workers have been on the front line,
| unvaccinated, for going on two years. To mandate it or
| risk being fired has absolutely pissed off quite a few
| that I know of... My wife has gotten it, and even she is
| offended.
|
| The hyperbole around this very serious situation just
| makes all the policies seem even more like theater.
|
| To your second point, there was just a new report I saw
| yesterday that there is no difference in viral load
| between asymptomatic vaccinated and unvaccinated
| individuals.
| LurkingPenguin wrote:
| > The hyperbole around this very serious situation just
| makes all the policies seem even more like theater.
|
| One has to conclude that it is theater at this point.
| Because the science is pretty darn clear.
|
| Interesting that nobody downvoting my comment (and yours)
| has posted a reputable and recent/current scientific
| source stating that:
|
| 1. Natural immunity is inferior to vaccine-based
| immunity.
|
| 2. Millions of Americans (perhaps 100 million according
| to a model developed by the CDC) haven't already had and
| recovered from COVID.
|
| 3. Vaccinated individuals can't become infected and
| spread the virus.
| macintux wrote:
| I'm definitely in the pro-vaccine, pro-mandate column,
| but both 1 and 3 from your list strike me as dubious
| given the information to this point. Certainly there's
| been conflicting information on both.
| LurkingPenguin wrote:
| Re-read my comment. I'm asking if anybody downvoting me
| can provide scientific evidence that those statements are
| true. Nobody has, because they're not.
|
| Natural immunity is durable and robust, and vaccinated
| people can get infected and spread the virus. In fact,
| according to the Israeli data, vaccinated people are
| magnitudes of order more likely to get a Delta
| breakthrough infection than a person with natural
| immunity is to get reinfected with Delta.
| howlong wrote:
| Why do we have vaccine mandates for people working from
| home?
| OrvalWintermute wrote:
| You've made an amazing claim, that infected healthcare
| workers, who, were caring for Covid patients for almost 2
| years now, have been spreading COVID further. This,
| despite the fact that they are most likely to have caught
| it early as they were caring for patients prior to
| vaccines, and hence to have obtained natural immunity.
|
| Please provide evidence to support your amazing claim.
| mmastrac wrote:
| I'm no policy or health care expert, but maybe because
| front-line and hospital workers are exposed to extremely
| large viral loads which seem to be related to the severity
| of the disease, and taking one HCW off the front-lines and
| adding them to the sick in the ICUs is worse than one less
| HCW and the same ICU level?
|
| This seems like you are trying to start a flamewar about
| vaccine mandates, BTW.
| nradov wrote:
| There's no reliable evidence that healthcare workers
| wearing proper PPE are exposed to extremely large viral
| loads. Nor is there evidence that symptom severity
| depends on initial viral load (beyond some minimum
| threshold for infection). It's a plausible hypothesis but
| the human challenge trials necessary to prove or disprove
| it haven't been done yet.
| kortex wrote:
| > Nor is there evidence that symptom severity depends on
| initial viral load (beyond some minimum threshold for
| infection).
|
| https://www.nature.com/articles/s41467-020-19057-5
|
| > It's a plausible hypothesis
|
| It's _extremely_ plausible, and been demonstrated before
| in influenza, poxviruses, and other viruses. The human
| challenge trials necessary to prove a dose-dependent
| relationship between fall height and lethality haven 't
| been conducted, either, but we have sufficient evidence
| from longitudinal and natural experiments to draw firm
| conclusions.
| nradov wrote:
| That study you linked isn't relevant to my point. The
| question is whether the initial viral dose at the point
| of infection is correlated with symptom severity later in
| the disease course. That remains unknown. The study
| looked at the relation between current viral load and
| symptoms _after_ infection, which is an entirely separate
| issue.
| twofornone wrote:
| Something extremely frustrating about virtually all
| reporting to date is that I haven't seen any statistics
| as to infection and reinfection rates among front line
| workers. The implication is that immunity post
| exposure/infection doesn't exist, but I suspect that this
| data is being deliberately withheld because it would
| suggest that frontline workers don't need vaccines, or at
| the very least don't need a mandate.
| rediguanayum wrote:
| The immediate parent comment is correct. Because Covid
| precluded elective surgery which is a major money maker for
| hospitals, the bottom line was hit. Consequently many
| hospitals cut back, and lot go physicians, PAs, nurses,
| techs, etc. When you hear hospitals are full, it very often
| isn't because of lack equipment or beds, but rather
| insufficient staff, especially nurses due to legal
| regulations around staffing ratios. (Source wife is a
| healthcare worker on the frontlines)
| _3u10 wrote:
| Because it helps reduce capacity which increases the
| political will for mandates.
| wyager wrote:
| If it's patented and they can make real money off it, maybe
| lsternlicht wrote:
| Phase 3 trial was stopped on a positive interim analysis by DSMB
| and in consultation with FDA
|
| Interim analysis was performed on approximately half of the total
| enrolled patients (775 of the 1550).
|
| Trial included many delta and other variant patients
|
| ----------
|
| Efficacy * ~50% reduction in hospitalization
| (14.1% PBO vs 7.3% drug) * 100% reduction in deaths (8
| PBO vs 0 drug)
|
| ----------
|
| Safety * fewer adverse reactions in the drug arm
| vs PBO (40% PBO vs 35% drug)
|
| ----------
|
| [Merck Ridgeback press release]
| https://www.businesswire.com/news/home/20211001005189/en/Mer...
|
| [clinicaltrials.gov]
| https://clinicaltrials.gov/ct2/show/NCT04575597?term=molnupi...
| divbzero wrote:
| Looks like the clinical trial was for age 18 and above so an
| EUA probably would not allow use in children.
| dham wrote:
| I mean I think that's ok at this point. Kids are at greater
| risk of a lot of other things before Covid. We're going to
| have to figure out how to get our kids to become nose
| breathers again and fix their enlarged adenoids.
| rory wrote:
| Is 40% adverse reaction to a placebo typical? Really makes me
| wonder how many "side effects" are in our heads..
| Pyramus wrote:
| Came here to say that it's not necessarily in our head - you
| can knowingly get a placebo and still react to it. As far as
| I know it's a combination of head, genetics and other unknown
| factors. In my opinion an underappreciated and understudied
| field.
| programmarchy wrote:
| Couldn't the adverse events in the placebo arm actually be
| caused by Covid?
| [deleted]
| nradov wrote:
| Probably. There was no uninfected control group.
| [deleted]
| linuxftw wrote:
| That depends. In the case of vaccines, the placebo is often
| all the ingredients of a vaccines minus the biological
| component, or in other cases, an already approved vaccine is
| used as the placebo.
|
| So, it's probably a poorly controlled study, or garbage
| results, or both.
| Confiks wrote:
| Keep in mind that _any_ negative effects, even those unlikely
| to be caused by the medication, need to be reported as
| adverse effects. It allows for making a clean comparison
| between the placebo, and also makes it possible to
| retroactively relate effects that have been overlooked
| previously. For example, you want 'patient was hit by a car'
| as possible side effect, because the medication could make
| people drowsy.
| rsynnott wrote:
| Given that this is a drug that's only given to people who
| _have covid_, I'd say it's incredibly difficult to
| disambiguate from covid symptoms.
| ashtonkem wrote:
| Covid and at least one comorbidity. 14% of the control
| group died; it's no surprise that 40% had _some_ sort of
| bad reaction, since presumably they were in pretty bad
| shape overall.
| PaulDavisThe1st wrote:
| Please read the excellent popular science book "Cure: A
| Journey into the Science of Mind Over Body" by
| author/journalist Jo Marchant. It gives an excellent overview
| of all things placebo related.
|
| ps. the answer to your question seems to be "quite a lot".
| barbazoo wrote:
| Disclaimer: I'm not promoting Ivermectin here, don't get me
| wrong. I just want to cover my bases as this announcement is
| definitely going to be used by people to support their conspiracy
| theory.
|
| Earlier this year Merck the manufacturer of Ivermectin issued
| this [0] statement saying that Ivermectin isn't useful for
| preventing/treating Covid-19 and people shouldn't take it. Some
| people explained that with the fact that Ivermectin is cheap and
| they want to develop a more expensive option. I didn't take this
| seriously, just another conspiracy theory. But now they are
| coming out with a $1000 per dose solution. According to the FDA
| [1], the use of Ivermectin for Covid-19 is still being studied
| and they refer to ongoing trials. Now some people with actual
| subject matter expertise will know more than me but afaik we
| haven't completely ruled out Ivermectin for the
| treatment/prevention of Covid-19, have we? If not, could there be
| some truth to the allegations that Merck somehow is stalling the
| Ivermectin studies?
|
| [0] https://www.merck.com/news/merck-statement-on-ivermectin-
| use...
|
| [1] https://www.fda.gov/consumers/consumer-updates/why-you-
| shoul...
| kungito wrote:
| There's an ongoing study:
| https://www.ox.ac.uk/news/2021-06-23-ivermectin-be-investiga...
| and I've also seen https://web.musc.edu/about/news-
| center/2021/09/17/trial-of-o...
|
| I've read elsewhere that the problem with Ivermectin treatment
| for covid is that the dosages showing results have to be higher
| than for previously tested usages of the drug so side effects
| are also not explored enough
| ruaraidh wrote:
| How could Merck stall those studies? Ivermectin is widely
| available, you don't need to get Merck's permission to use it
| in a study.
| mywittyname wrote:
| The FDA isn't immune to the same kind of corruption/conflicts
| of interest that impacts other federal agencies.
|
| Scott Gottlieb worked at the FDA at a high level, before
| leaving for a stint in the private sector which included
| being a partner in a VC fund which invested in many medical
| startups. He left that to become the commissioner of the FDA
| under the previous administration. Gottlieb is currently on
| the board of Pfizer, and has relationships with several other
| companies in the pharma space.
|
| It's not insane to think this person still has sway with
| people who are working within the FDA and are considering a
| move to the private sector.
| barbazoo wrote:
| That's a good point, thanks.
| twofornone wrote:
| >A concerning lack of safety data in the majority of studies.
|
| This is the part of Merck's statement that really rubs me the
| wrong way, and suggests to me that this communication was
| released with an agenda. The implication is that one of our
| safest, 60+ year old medications is suddenly potentially
| dangerous, and this press release is all too convenient when
| you consider that Merck was working on newer and more
| profitable alternatives.
| kortex wrote:
| The dosing regime purported to be most effective against
| covid is way higher than the antiparasitic therapeutic
| window, so the safety history is not as applicable.
| kortex wrote:
| The problem is that if the in-vitro studies are correct on
| their dose curves, then the majority of the human trials are at
| ineffective doses. This doesn't mean they _must_ be wrong, but
| it 's not a good look. If the studies were showing unequivocal
| benefit, we could overlook the dose curves. But the studies are
| still quite equivocal.
|
| On the other hand, molnupirivir is a nucleoside polymerase
| inhibitor, with a slam-dunk mechanism of action, evidence of
| efficacy against a broad range of viruses, and increasingly
| compelling human safety profile.
|
| I don't know if Merck is _stalling_ but the ivermectin case is
| certainly less compelling.
|
| https://www.science.org/content/blog-post/ivermectin-covid-1...
| ashtonkem wrote:
| Those in vitro studies were done with Vero cells, from the
| kidneys of a green monkey, which do not appear to be a good
| analogue for human lung cells with Covid. Even if you could
| give the Ivermectin doses recommended by the study without
| killing the patient, chances are it wouldn't actually work.
| tedunangst wrote:
| Drug companies have lots of products. Did J&J discontinue their
| baby powder because they secretly knew talc powder cures covid
| but they wanted to sell more vaccines?
| dougmwne wrote:
| Here is why this is a conspiracy theory and likely complete
| bull: there are 190 somthing countries in the world. Many of
| them have public health systems with socialized healthcare.
| Many of them are completely free of influence from Merck or the
| FDA. Ivermectin is cheap and widely available. There is no way
| Merck and the FDA could suppress a global consensus if the drug
| was strongly effective.
|
| Conspiracy thinking often relies on a simplified model of the
| world, one in which other countries, other governments, and
| other healthcare systems simply do not exist. One where a
| single centralized entity could have ironclad control over a
| messy, complex and heterogeneous world.
|
| If you are engaging in these patterns of thinking, I recommend
| you step back, get out of your bubble and your normal context,
| diversify your information diet and try to ask more pointed
| questions of the viewpoints you are taking in. And please stop
| wiggling your eyebrows at us.
| barbazoo wrote:
| > If you are engaging in these patterns of thinking, I
| recommend you step back, get out of your bubble and your
| normal context, diversify your information diet and try to
| ask more pointed questions of the viewpoints you are taking
| in. And please stop wiggling your eyebrows at us.
|
| I am not. I clearly pointed out that I think this is a
| conspiracy theory. However I should still be allowed to ask
| questions that help me point people that believe in these
| conspiracy theories into the right direction. That doesn't
| make me a conspiracy theorist.
| dougmwne wrote:
| > If not, could there be some truth to the allegations that
| Merck somehow is stalling the Ivermectin studies?
|
| You are holding this conspiracy theory up as something that
| should be discussed and considered as possible truth. You
| didn't say you believed it, only that it was worth our
| attention.
| bshoemaker wrote:
| Is there any evidence they are?
|
| Otherwise, that sounds like a conspiracy theory itself.
| barbazoo wrote:
| Not that I know if. I'm a layman I know pretty much nothing
| in that field so I'm just having a hard time dismissing the
| whole Ivermectin thing. Especially now that Merck will make a
| boatload of money with their new drug.
|
| If I was Merck and I had a drug #1 that costs a few cents
| that might work and I can develop a new drug #2 that will
| cost $1000, then I'd probably not look into #1 much simply
| for financial reasons.
|
| That might not be how it works but I simply don't know that.
| bshoemaker wrote:
| Sure, but you're suggesting that they are doing that
| without any evidence.
|
| This is classic conspiracy theorist rhetoric, whether
| that's your intention or not.
| barbazoo wrote:
| Sorry, I don't know how else to question the conspiracy
| theory itself without mentioning the conspiracy theory. I
| even called it a conspiracy theory.
| skrtskrt wrote:
| I mean I think "some large entity (government, pharma
| company, facebook, etc) is screwing us over to make a ton of
| money or enact their agenda" is an idea that most people are
| pretty happy to subscribe to across the political spectrum,
| particularly in America.
|
| Part of it is because we can see this shit happening in real
| time now - Epipen prices getting jacked up by the daughter of
| the currently-most-consequential senator (Manchin), who is
| basically refusing to enact even basic Democratic agenda
| items particularly in regards to healthcare, etc etc.
|
| These theories just take on a different flavor depending
| where you are on the political spectrum. If you're on the
| right, Facebook is silencing right wing voices. if you're on
| the left, Facebook is silencing left wing voices, etc.
| [deleted]
| henryw wrote:
| Atea Pharmaceutical is finishing up phase 3 trial of a Covid
| anti-viral pill in November that might be more effective (based
| on phase 2 trial data) and doesn't mutate the virus:
| https://ateapharma.com/at-527/
| [deleted]
| yumraj wrote:
| Genuinely curios, and the time will tell, if the vaccine sceptics
| will be more open to the pill, or if they will be equally/more
| sceptic of the pill also.
| photochemsyn wrote:
| Some interesting points on the nature of our pharmaceutical
| patent system... (and while the cohort in this study does seem a
| bit small, the conclusions appear to be fairly valid):
|
| > "Molnupiravir was invented at Drug Innovations at Emory
| (DRIVE), LLC, a not-for-profit biotechnology company wholly owned
| by Emory University, and is being developed by Merck & Co., Inc.
| in collaboration with Ridgeback Biotherapeutics."
|
| > "In fiscal year 2019, more than half of Emory's total $689.1
| million in research funding came from the federal government, the
| university's largest sponsor."
|
| Clearly, this patent should be assigned to the federal
| government, not to Merck, and anyone who wants to manufacture and
| distribute it should be able to do so under an non-exclusive
| federal licensing program. The transfer of intellectual property
| created by the public funds to private entities is simply a
| criminal ripoff of the taxpayer.
|
| [edit] Wait, was this a three-week clinical phase III trial?
| Seems massively expedited relative to other phase III trials?
|
| > "Phase 3: Just 33% of drugs make it past Phase 2 and into Phase
| 3, which tests the potential treatment in the largest number of
| people. This phase measures both safety and effectiveness with
| many volunteers, sometimes thousands. Phase 3 trials last from
| one to four years."
|
| Trial began on Sept 2 2021 apparently?
|
| 1. https://www.clinicaltrialsarena.com/news/merck-ridgeback-
| mol...
| dbcooper wrote:
| Why do people here always want to reduce the equity and income
| of pharma and biotech scientists?
| mhb wrote:
| It must be because they have extensively modeled the optimal
| societal benefit of reducing the financial incentive to these
| entities.
| jrockway wrote:
| I don't think investing money necessarily transfers the
| ownership of things bought with that money to the investor. The
| government could put in their contract "we get all your drugs
| that you invent" if they wanted that. But this would be like
| startup VCs getting 100% of your company, or your bank getting
| the appreciation on your house when you sell it, etc. They
| could ask for those things, and you could say no... and most
| people do say no.
|
| The government wants to focus research into particular areas,
| not compete with the pharmaceutical companies. (At least the
| money isn't for making a new advertising platform, which is
| probably something a VC would fund in a heartbeat. Drug
| discovery is too risky for them.)
|
| You may disagree with that, but that's their intent. If you
| want the government to be discovering drugs and testing them,
| definitely tell your elected representatives that that's what
| you want, and the system can change. (Or get rich from an
| advertising platform and do it yourself! ;)
| akira2501 wrote:
| > The government could put in their contract "we get all your
| drugs that you invent" if they wanted that.
|
| "The government" isn't an entity that can unilaterally decide
| anything. I think it's incredibly revealing that very little
| of this process is understood or publicized.
| avianlyric wrote:
| Even the VCs get a better deal here, they end up with equity.
| If followed that model, then the taxpayer would own at least
| 50% of the patents generated (via shares the corporate entity
| that owned the patents).
|
| Under the current model the taxpayer gets nothing, which
| hardly seems reasonable given the amount of capital they
| provide.
| BobbyJo wrote:
| Don't we already own a portion of what gets created though?
| If Merck makes a boatload of money off of this, the
| taxpayers will indeed be taking a cut.
| ipaddr wrote:
| No we decided that corporate taxes should be low so the
| company can reinvest. The shareholders benefit.
| callmeal wrote:
| >If Merck makes a boatload of money off of this, the
| taxpayers will indeed be taking a cut.
|
| Merck's effective tax rate was 15% in 2019 and 20% in
| 2020[0]
|
| They make boatloads of money by underpaying their taxes
| [1]: In 2004 Merck disclosed that it
| might owe the U.S. Internal Revenue Service (IRS) some $2
| billion after the agency notified the company that it was
| disallowing deductions Merck had taken since 1993
| relating to a partnership set up in 2003 as a vehicle for
| obtaining financing for the acquisition of Medco.
| In 2006 the Wall Street Journal reported that Merck had
| set up a subsidiary in Bermuda that, in partnership with
| a British bank, was given title to the patents for the
| company's blockbuster cholesterol drugs Zocor and
| Mevacor, thus saving Merck an estimated $1.5 billion in
| federal taxes over ten years. Shortly
| thereafter, Merck disclosed that it was embroiled in four
| separate tax disputes in the United States and Canada
| with total potential liabilities of more than $5 billion.
| In 2007 the IRS announced that Merck had agreed to pay
| $2.3 billion to settle its federal tax disputes.
|
| They also make additional boatloads of money overcharging
| Medicare/Medicaid: In 2008 Merck agreed
| to pay the federal government more than $650 million to
| settle charges that the company routinely overbilled
| Medicaid and other government programs and made illegal
| payments to healthcare professionals to induce them to
| prescribe its products. In December 2011 the
| Massachusetts attorney general announced that Merck would
| pay $24 million as its part of a $47 million settlement
| reached with 13 drugmakers to resolve allegations that
| they overcharged the state's Medicaid program.
| In 2012 the Louisiana attorney general announced that
| Merck and four other companies would pay a total of $25.2
| million to resolve allegations that they overcharged the
| state's Medicaid program.
|
| [0] https://www.stock-analysis-on.net/NYSE/Company/Merck-
| Co-Inc/... [1] https://www.corp-research.org/merck
| BobbyJo wrote:
| That's 15%-20% we the taxpayers own then :)
| photochemsyn wrote:
| I think a better option is for the pharmaceutical
| corporations themselves to reduce both their advertising
| budget and their shareholder dividends and pour those funds
| into their own independently financed research institutes
| (see Bell Labs for the model followed in the past).
|
| The best way to encourage them to do this is to eliminate
| exclusive licensing of inventions financed even in part by
| the taxpayer, i.e. NIH, NSF funding etc. Under this model,
| Merck would still be able to produce the drug but any other
| competitor could also produce the drug, and then you'd have a
| competitive production process (see steel production etc.)
| which would, I believe, create the highest quality products
| at the lowest cost to the consumer.
| b9a2cab5 wrote:
| Where is the motivation for Merck to pour funds into a drug
| they don't get any return on?
|
| And if the government is doing this R&D instead of pharma
| cos, what is their motivation to perform? If you're a
| government apparatchik making decisions about what drugs to
| invest into R&D for, what penalty and upside do you get for
| being wrong/right? Getting fired or getting a promotion?
| That's hardly motivating at all.
|
| Your proposal has terrible incentives for everyone all
| around and would certainly reduce innovation in the long
| run.
| inglor_cz wrote:
| Regarding your edit: there isn't any shortage of covid-exposed
| people right now.
|
| Often, trials lag because not enough participants fulfilling
| the criteria can be recruited. This is especially pronounced in
| rarer diseases.
|
| Plus, you will know outcomes of covid pretty quickly. Compared
| to diseases such as Alzheimer or multiple sclerosis, covid
| develops fast.
| OrvalWintermute wrote:
| We would need to examine the research proposals, and the data
| rights included in them, and if any other institutions
| providing matching funds, that resulted in this drug.
|
| Having said that, I broadly concur that we need to examine to
| what extent the federal government, and all of us taxpayers,
| should own outright some, or all as a % of the IP.
| rich_sasha wrote:
| > Clearly, this patent should be assigned to the federal
| government, not to Merck
|
| How about a proportional slice? That would seem fair. IP and
| products can have fractional ownership.
| mhb wrote:
| What does "fair" have to do with anything? Are you suggesting
| that your proposal maximizes the amount of health-improving
| interventions that society will receive in the future? Do you
| have any reason to conclude that what you're suggesting will
| be even a slight improvement?
| rich_sasha wrote:
| You're sounding rather aggressive.
|
| It seems reasonable that if I finance X% of something, I
| get to enjoy X% of it. Or Y%, adjusted for non-monetary
| investment by someone else.
|
| It seems strange that the state finances (drug development)
| research, the companies say "cheers" and proceed to keep
| all the profits.
|
| Such profits could for example go towards universal health
| care improvements.
| mhb wrote:
| Maybe we want different things from the US government and
| its health care system. I'd like to optimize health
| outcomes. You have some proposals. Can you explain how
| they lead to something better than the status quo? What
| are the unintended consequences? Do drug companies invest
| in less drug development if they get X% less from
| developing drugs? Have you taken this into account in
| your advocacy for enjoying the X%?
|
| Or maybe you have a different objective?
| loeg wrote:
| As a taxpayer / healthcare consumer who is not employed in
| pharma -- yeah, it would be nice if we (the US) did a
| little less subsidizing of drug development for the rest of
| the world. Proportional ownership of sponsored drugs seems
| like a nicely aligned incentive. What am I missing?
| mhb wrote:
| I don't know how the pharma industry decides what to
| pursue, but it is at least plausible that part of the
| incentive for what they do depends on being able to price
| discriminate in sales to other countries. Before
| suggesting we tear down Chesterton's fence, it seems
| reasonable that you should have more justification than
| just that it seems fair to you.
| loeg wrote:
| I don't understand your concern -- how does proportional
| ownership eliminate pharma's ability to price
| discriminate? I just think the US government should
| receive some prorated portion of profits from drugs they
| subsidized development of, which can be reinvested into
| further development.
| mhb wrote:
| These are separate issues. You said that the US is
| subsidizing drug development for other countries and
| suggested that you would prefer that we didn't. That
| affects drug development incentives.
|
| You're also saying that the US government should have
| some of the profits that the drug companies currently
| have. Presumably this would affect something that drug
| companies do. Shouldn't you be concerned that the thing
| it will affect is them developing new drugs?
|
| Maybe the current situation isn't optimal but there's no
| reason to think that your suggestions would improve
| things.
| photochemsyn wrote:
| Ultimately the issue is the licensing of the patent (which is
| likely retained by Emory or its non-profit affiliate), and
| under Bayh-Dole universities can exclusively license it.
|
| By introducing non-exclusive licensing, then you have a
| competitive situation in which the lower-cost manufacturer
| can provide the drug more cheaply but at the same quality and
| monopolistic pricing schedules cannot be introduced by the
| likes of Merck.
|
| The taxpayer benefit is lower cost of drugs invented with
| taxpayer funds.
| allturtles wrote:
| This is a consequence of the Bayh-Dole Act
| (https://en.wikipedia.org/wiki/Bayh%E2%80%93Dole_Act).
| sjg007 wrote:
| You can thank Bob Dole for that wrt patents from Federal
| research funds.
| mywittyname wrote:
| TIL.
|
| I'm slowly learning that, when the government has a choice
| between and obvious, smart way of operating, and a clearly
| dumb way. They choose the dumb way because some chucklefucks
| in Congress made it illegal to operate the smart way.
| ashtonkem wrote:
| The phase III trial was cut short at the recommendation of the
| independent monitoring board. Apparently the effect was so
| strong they recommended seeking Emergency Use Authorization
| earlier, rather than waiting for the trial to finish,
| presumably so that they could save more people's lives who
| might get sick and die waiting for trials to finish.
| shusaku wrote:
| https://www.nytimes.com/2021/10/01/us/merck-antiviral-pill-c...
|
| The NYTimes article sort of came off as suggesting this is a
| cheaper, easier to administer alternative to monoclonal
| antibodies. So I wonder what the overall effect will be on the
| number of deaths going forward. It's definitely phenomenal
| science though, and hopefully we can use this to keep people out
| of the hospital!
| nradov wrote:
| The mechanisms of action are different. I expect clinicians
| would want to use both, at least for high risk cases.
| clairity wrote:
| the interview i heard this morning indivcated that there's also
| a big unknown around whether it can induce genetic mutation
| (presumably in gametes). (male) participants were advised
| against (unprotected?) sex during the trials to prevent
| potential future problems with progeny.
| SamBam wrote:
| Male and female participants were required to abstain from
| unprotected sex.
| WaitWaitWha wrote:
| This is not my field. But if there is a pill that can reduce
| death by 50% from the virus, I would like to know more about it.
|
| > Bright's concerns that similar drugs in its class have
| mutagenic properties
|
| As a layperson, this instantly raises a red flag in my mind.
| Should I be concerned? Why, or why not? More importantly, where
| can I find research that elucidates this for me?
| WaitWaitWha wrote:
| >That's the effect of NHC and of molnupiravir. What about the
| bad side? Well, auxh nucleosides can also be taken up by many
| other enzymes, including those that handle our own nucleic
| acids, so some of them are mutagenic. Indeed, that's how NHC
| was first characterized, as a mutagen in bacteria. They also
| tend to be cytotoxic, via a number of mechanisms, and
| nucleoside drug candidates are notorious for wiping out in
| human trials due to toxicity in the liver, kidneys, and other
| organs. That was a feature of the 2012 scramble in the
| hepatitis C area, where Bristol-Myers Squibb paid 2.5 billion
| for a nucleoside addition to its proposed therapeutic cocktail,
| only to see it all demolished within a few months when it
| turned out to have severe problems in human trials. From this
| story and others you can also conclude that you don't
| necessarily get a good reading on this stuff in animal trials -
| another feature of Fun With Nucleosides.[0](Derek Lowe)
|
| [0] https://www.science.org/content/blog-post/molnupiravir-
| last-...
|
| (edit: this is just a note I found, does not solve why/why not
| in my mind)
| vsef wrote:
| There are quite a few nucleoside analogues that have been
| used for HIV treatment: AZT, Zerit, FTC, Videx, Abacavir,
| 3TC, Hivid. There may be others I'm missing.
|
| Of these, only Abacavir and FTC (as part of Truvada) are
| still used, the others have fallen out of use or are no
| longer even manufactured due to their bad side effect
| profiles and propensity for severe adverse reactions. 'Nuke-
| sparing' regimen planning specifically would combine other
| classes of drugs to avoid this class due to side effect
| issues.
|
| I think it's great to have this new treatment option but this
| class of medications is well known for its side effects.
| Avoiding vaccines as 'unproven' and then going for this in
| particular I would consider eye rollingly wrong headed.
| dbbk wrote:
| It reduces death by 100%. It's hospitalisation that's reduced
| by 50%.
| OrvalWintermute wrote:
| I'm not sure if this is tightly related, but here is Bright's
| whistleblower complaint [1] because it seems that mutagenic
| concerns are a different issue?
|
| [1] https://s3.documentcloud.org/documents/6882540/R-Bright-
| OSC-...
| kortex wrote:
| P13-14:
|
| > During the meeting, Dr. Painter and Mr. Clerici presented a
| drug, EIDD-2801, as a "cure all" for influenza, Ebola, and
| nearly every other virus.
|
| > They requested that BARDA urgently invest millions of
| dollars into their "miracle cure." Emory's presentation
| included limited data, and no data at all from human trials.
| Dr. Bright asked targeted questions to understand the science
| behind the drug and its potential to safely treat patients.
| Dr. Bright knew that similar experimental drugs in this class
| had been shown to cause reproductive toxicity in animals, and
| offspring from treated animals had been born without teeth
| and without parts of their skulls. Dr. Bright accordingly
| asked Dr. Painter and Mr. Clerici about clinical trials,
| including whether Emory had conducted a reproductive study
| for toxicity, which they had not.
| kortex wrote:
| Molnupiravir, being a polymerase inhibitor (in layman's terms
| it "jams up replication machinery"), has the potential for
| mutagenicity. In fact it was dropped by a Gilead subsidiary for
| this exact reason. [1]
|
| > A company called Pharmasset Inc. (a hepatitis C drugmaker
| Gilead bought in 2011) investigated molnupiravir's main
| ingredient around the turn of the century, but it abandoned
| development over concerns that it was mutagenic, meaning it
| could lead to birth defects.
|
| Actually the article is slightly wrong, mutagenic is causing
| mutations in the host's germ or somatic DNA, teratogenic is
| causing birth defects. Most mutagens are teratogens too. From
| the Dr Bright complaint filing, Bright was concerned about
| reproductive toxicity (teratogenicity) so I'm not sure if the
| article meant to say teratogenic, or the concern is that the
| drug is both mutagenic and teratogenic (polymerase drugs tend
| to be both).
|
| Subsequent tests seem to have shown a lack of mutagenic
| activity in hosts (eg Painter 2021), at least enough to get
| through safety trials, which is excellent. But looking at it
| from a structural activity point of view, molnupiravir is way,
| way more likely to have a DNA-affecting mechanism than mRNA. It
| has also shown mutagenic effect in vitro [2]. Nonetheless, a
| small increase in cancer risk years down the road (especially
| in the over-70 crowd) is likely worth the 50% (!) reduction in
| mortality.
|
| It's probably fine, as long as you aren't pregnant. Like all
| drugs, it's about risk/benefit ratio. The covid vaccine has a
| much more favorable profile and should still be the preferred
| option. I doubt it'll be approved for pregnant women without a
| reproductive toxicity study.
|
| 1 - https://www.bloomberg.com/news/features/2021-03-25/merck-
| mrk...
|
| 2 - https://pesquisa.bvsalud.org/global-literature-on-novel-
| coro...
|
| Search for 'b-D-N4-hydroxycytidine safety' if you wanna dig
| deep.
| zxcb1 wrote:
| It's a program that incorporates itself into another program
| while at the same time corrupting the program, and after several
| iterations there is a catastrophic failure.
| tiahura wrote:
| The Ridgeback founders were on CNBC this morning in a very
| encouraging interview. A few takeaways: 1. They are testing now
| as a prophylactic and anticipate positive results. 2. The
| mechanism of action is different from the upcoming Pfizer pill,
| so it's reasonable to expect they can be taken together as a
| cocktail for even better outcomes. 3. It is showing positive
| results with other viruses in animals.
|
| Cool stuff!
| elliekelly wrote:
| > The Ridgeback founders were on CNBC this morning in a very
| encouraging interview.
|
| This just feels wrong and makes me uncomfortable for reasons
| I'm not quite able to articulate.
| tiahura wrote:
| Why? It's my understanding that this flows from work done
| years ago at Emory University. With the exciting news, why
| shouldn't they take a bit of a victory lap? Good for them.
| rflec028 wrote:
| Ivermectin is inexpensive to manufacture, is extremely safe, and
| is currently being used by many countries to both treat and
| prevent the spread of covid.
|
| Molnupiravir had concerns during its development of the drug
| having mutagagenic properties.
|
| Why not just use the inexpensive, safe, proven effective
| medication?
| dougmwne wrote:
| Please don't post dangerous disinformation to HN. That drug is
| not an approved treatment for COVID.
| MisterBastahrd wrote:
| There aren't any first-world countries using ivermectin to
| treat or prevent the spread of COVID.
|
| Because ivermectin is roundworm poison, not an antiviral. The
| countries were desperate to try ANYTHING, and it was the best
| they could get their hands on at the time. They were prompted
| to action because ivermectin affected COVID in lab experiments,
| not in actual cases, and the result of the use in those
| countries were that ICUs were inundated by people who were
| taking said poison.
| barbazoo wrote:
| I'm curious to know if there are studies involving actual
| Covid-19 cases being treated with Ivermectin. If not, why? If
| yes, what are the results?
| raphlinus wrote:
| Yes, there are 14 studies that met the criteria for
| inclusion in the Cochrane review of Ivermectin. The results
| are mixed (some show a bit of improvement) but overall
| weak.
|
| In addition, ACTIV-6 is a massive (15,000 participant)
| study that will study Ivermectin and two other repurposed
| medications. Because that study is large and rigorous, it
| will basically answer the question of whether Ivermectin
| works and how well.
|
| [1]: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651
| 858.CD...
|
| [2]: https://dcri.org/activ-6-study/
| barbazoo wrote:
| I'll definitely look at and follow those, thanks.
| decebalus1 wrote:
| Disinformation kills. Please don't spread that here.
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