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.
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.
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.
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."
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.
> 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.
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?
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.
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.
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
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?
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.
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?
>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)
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?
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.
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/
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!
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.
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."
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.
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.
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.
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.
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?
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.
Reduced from 14% to 7% risk. Would be nice to see how it compares to other off-label treatments such as Ivermectin which has had great success in India.
[+] [-] carbocation|4 years ago|reply
As an MD, the difference between calling in a script for a pill and arranging for outpatient infusion therapies is vast.
[+] [-] andybak|4 years ago|reply
[+] [-] dougmwne|4 years ago|reply
[+] [-] sudosysgen|4 years ago|reply
[+] [-] stevespang|4 years ago|reply
[deleted]
[+] [-] unknown|4 years ago|reply
[deleted]
[+] [-] SideburnsOfDoom|4 years ago|reply
Welcome to the "intelligentsia" debating anti-Covid measures. On the topic, you usually see worse than this.
[+] [-] photochemsyn|4 years ago|reply
> "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...
[+] [-] lsternlicht|4 years ago|reply
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
—————Safety
—————[Merck Ridgeback press release] https://www.businesswire.com/news/home/20211001005189/en/Mer...
[clinicaltrials.gov] https://clinicaltrials.gov/ct2/show/NCT04575597?term=molnupi...
[+] [-] _Microft|4 years ago|reply
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
[+] [-] DominikPeters|4 years ago|reply
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|4 years ago|reply
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.
[+] [-] jonnycomputer|4 years ago|reply
[+] [-] AndrewBissell|4 years ago|reply
https://pesquisa.bvsalud.org/global-literature-on-novel-coro...
[+] [-] barbazoo|4 years ago|reply
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...
[+] [-] dougmwne|4 years ago|reply
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.
[+] [-] kortex|4 years ago|reply
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...
[+] [-] ruaraidh|4 years ago|reply
[+] [-] bshoemaker|4 years ago|reply
Otherwise, that sounds like a conspiracy theory itself.
[+] [-] kungito|4 years ago|reply
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
[+] [-] coryrc|4 years ago|reply
[+] [-] tedunangst|4 years ago|reply
[+] [-] davidw|4 years ago|reply
[+] [-] rossdavidh|4 years ago|reply
[+] [-] WaitWaitWha|4 years ago|reply
> 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|4 years ago|reply
[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)
[+] [-] OrvalWintermute|4 years ago|reply
[1] https://s3.documentcloud.org/documents/6882540/R-Bright-OSC-...
[+] [-] kortex|4 years ago|reply
> 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 'β-D-N4-hydroxycytidine safety' if you wanna dig deep.
[+] [-] dbbk|4 years ago|reply
[+] [-] henryw|4 years ago|reply
[+] [-] shusaku|4 years ago|reply
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|4 years ago|reply
[+] [-] clairity|4 years ago|reply
[+] [-] endisneigh|4 years ago|reply
[+] [-] admeyer|4 years ago|reply
"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|4 years ago|reply
[+] [-] TrevorJ|4 years ago|reply
[+] [-] mmastrac|4 years ago|reply
[+] [-] mc32|4 years ago|reply
[+] [-] mmastrac|4 years ago|reply
[+] [-] gizmo686|4 years ago|reply
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|4 years ago|reply
[+] [-] wyager|4 years ago|reply
[+] [-] tiahura|4 years ago|reply
Cool stuff!
[+] [-] elliekelly|4 years ago|reply
This just feels wrong and makes me uncomfortable for reasons I’m not quite able to articulate.
[+] [-] paulgdp|4 years ago|reply
https://twitter.com/bert_hu_bert/status/1444018619059429377
[+] [-] nikolay|4 years ago|reply
[+] [-] zxcb1|4 years ago|reply
[+] [-] unknown|4 years ago|reply
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[+] [-] JakeAl|4 years ago|reply