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Medicine

Meet Molnupiravir, Merck's Pill That Cuts COVID-19 Hospitalization and Death By About Half (arstechnica.com) 181

Posted by BeauHD from the Thor-inspired dept.
An anonymous reader quotes a report from Ars Technica: An oral antiviral drug appears to cut the risk of hospitalization and death from COVID-19 by roughly 50 percent in people newly diagnosed with the infection and at risk for severe disease, pharmaceutical company Merck announced Friday morning. The drug-maker and its partner, Ridgeback Biotherapeutics, released top-line results of a Phase III trial, which the companies ended early given the positive results. The companies say they will apply for an Emergency Use Authorization from the US Food and Drug Administration as soon as possible.

The trial enrolled people who had newly tested positive for a SARS-CoV-2 infection and had onset of mild-to-moderate COVID-19 symptoms within just the past five days of starting the trial. The enrollees also had to have at least one risk factor for a poor outcome, such as having obesity, diabetes, heart disease, or being age 60 or above. While some participants received a placebo and standard care, others took an oral dose of the drug every 12 hours for five days. After 29 days of follow-up, 53 out of 377 participants who received the placebo were hospitalized with COVID-19, and eight of those participants died. Among those who received the drug, only 28 of 385 were hospitalized and none of those patients died. Put another way, 7.3 percent of patients on the drug were either hospitalized or died compared with 14.1 percent in the placebo group. Merck also highlighted that the trial was global and that the drug appeared to work equally well against varying SARS-CoV-2 variants, including delta, gamma, and mu. The drug-maker noted that it had viral genetic data to identify variants from 40 percent of participants. The safety data was equally promising, with participants reporting similar numbers of drug-related adverse events between the placebo group than the drug group (11 percent and 12 percent, respectively). About 3.4 percent of people in the placebo group quit the study due to adverse events, while only 1.3 percent quit in the drug group.

The drug at the center of these seemingly smashing results is dubbed molnupiravir -- a name inspired by that of Thor's hammer, Mjolnir. The idea is that the drug will strike down SARS-CoV-2, like a mighty blow from the god of thunder. In an interview with Stat news, Merck's head of research and development, Dean Li, said that the new data proves the drug's mythological force. "Our prediction from our in vitro studies and now with this data is that molnupiravir is named after the right [thing]... this is a hammer against SARS-CoV-2 regardless of the variant." Molnupiravir is a small molecule that wallops the work of a viral RNA-dependent RNA polymerase, an enzyme critical for making copies of RNA viruses, such as SARS-CoV-2. [...] Molnupiravir delivers a precise blow to viral RNA polymerase by posing as a building block for RNA. In the body, molnupiravir is forged into a deceptive ribonucleoside that the polymerase unwittingly incorporates into new strands of viral RNA instead of cytidine. This is essentially lethal. Researchers call the effect a "viral error catastrophe," in which the rate of genetic mutations or errors exceeds a threshold compatible with the virus surviving.
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Meet Molnupiravir, Merck's Pill That Cuts COVID-19 Hospitalization and Death By About Half More

Meet Molnupiravir, Merck's Pill That Cuts COVID-19 Hospitalization and Death By About Half

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  • Windows of efficacy (Score:5, Informative)

    by lilneddygoestowar ( 8478105 ) on Friday October 01, 2021 @10:44PM (#61852845)
    I am not going to comment on the efficacy of this treatment. Studies are coming out at lighting pace with different treatments and different patient populations. What I can speak to is my experience with patients that have been diagnosed with Covid. From what I have seen (anecdotal) alot of these patients stay home and fool themselves into thinking it is only an allergy or the flu. They will do this for over two weeks if they can, and at that point it sounds like the window is closed for this treatment. The same holds true with Florida and the monoclonal antibodies. Yes, they do help you recover a bit faster, BUT you have to admit you are sick with covid within ten days of agreeing to taking that medication. The mental gymnastics of a-lot of these anti vaxxers have performed is truly at a Simone Biles level. And when they end up in the ICU they ask for these therapeutics that are outside of their efficiently window.

    • Re: (Score:3)

      by Luthair ( 847766 )
      I think another unfortunate side effect is that it will give people another excuse not to get vaccinated.

      • Re: (Score:3, Insightful)

        by ArmoredDragon ( 3450605 )

        I don't know about that, the ones who aren't vaccinated at this point probably aren't ever going to get vaccinated, unless they're impacted by some sort of mandate to do so that they can't get around with a fake vaccine card or a feigned religious exemption.

        Besides, they'd likely refuse this treatment if offered it. I could see iggymanz on his death bed saying "it's only emergency use authorization, it's not approved!" and refusing it, then asking for ivermectin, even though it doesn't even have emergency u

        • This response was that when the air hunger sets in everybody shows up at the ER. The phrase air hunger really stuck with me...

        • Re: (Score:2)

          by Luthair ( 847766 )

          I don't know about that, the ones who aren't vaccinated at this point probably aren't ever going to get vaccinated, unless they're impacted by some sort of mandate to do so that they can't get around with a fake vaccine card or a feigned religious exemption.

          I believe there is some part of the population which hasn't gotten around to it, or has been frightened by the constant FUD from anti-vaxxers and right-wing nutjobs.

          On a side note, I can't help but comment on how the typical self-identified "left wing" constantly railed about how evil big pharma is, including spreading big conspiracy theories about it, until now, during a pandemic, they suddenly realize that the US really is at the forefront of modern medicine after all. The US is and has for a very long time been subsidizing health care research for the rest of the world, who end up getting our medication at a steep discount when it's all said and done. And of course, after the pandemic ends, they'll go back to saying it's evil again.

          This is a completely fictitious straw man argument, the complaint that the "left" (and probably no small part of the "right") has against big pharmaceutical corps are business practices.

      • Re: (Score:3)

        by AmiMoJo ( 196126 )

        Or to stock up on this stuff. Back when there was a bird flu epidemic the UK government made the treatment freely available. You had to send someone who wasn't infected to the pharmacy to get it for you. Of course a lot of people went and got some even if nobody was sick, "just in case". They were often quite open about doing it as well.

        It might be a British thing. Low confidence and trust in the government is currently causing petrol shortages.

        • Re: (Score:2)

          by jebrick ( 164096 )

          It might be a British thing. Low confidence and trust in the government is currently causing petrol shortages.

          Or they kicked out 100,000 truckers during Brexit and now find that they do not have enough truckers to deliver goods.

      • Comment removed based on user account deletion

        • Re: (Score:2)

          by Luthair ( 847766 )
          Unfortunately due to laziness, the FUD spread by anti-vaxxers, and right-wing nutters there is a portion of the population which isn't necessarily adverse to the idea of vaccination but has reasons about why they haven't gotten around to it, or why they're scared to do it.

      • I think another unfortunate side effect is that it will give people another excuse not to get vaccinated.

        That's easily solved by giving it free to anyone who has been properly vaccinated, and making anyone unvaccinated pay through the nose.

      • This comment here should really be at 5.
    • Yes, the mAb treatments are only effective in the beginning stages. That's why I think we need ubiquitous testing! I'm talking at-home, take one when you are feeling a little sick. If positive, go get mAb - done.

    • As an aside about efficacy. Roughly 35% in the trial with molnupiravir reported side effects, but 40% who had the placebo reported side effects!

    • In the long term covid-19 seems to look to have staying power - if only because enough idiots let themselves be virus mothership. But for those3 of us which are vaccinated, try to live masked, follow distancing rules, if we get contaminated by them ? This will help us, because I dunno for you but I ain't waiting 2 weeks now to go to the doc in case of cold. And THAT will be helping us.

  • After 29 days of follow-up, 53 out of 377 participants who received the placebo were hospitalized with COVID-19, and eight of those participants died.

    And the ethics board?

    • Not sure what else could be done in terms of ethics, other than running the trial just like it was.

      As in, if you gave the drug to all the 377+385 patients in the study, you could still count out 762 patients who didn't get the drug, and observe them. If you gave the drug to 1500 patients, there would still be 1500 patients not receiving it.

      Basically, unless you gave an untested drug to the entire population, there would be someone not receiving it. Observing those not receiving it isn't any more unethical t

      • There has been examples of where when a working treatment was found, the trial was cut short and the placebo group given what the other group had.

        • Re:Playing the odds. (Score:4, Informative)

          by burtosis ( 1124179 ) on Friday October 01, 2021 @11:56PM (#61852965)
          This trial actually was cut short [washingtonpost.com] due to its positive results.

        • Re:Playing the odds. (Score:4, Informative)

          by As_I_Please ( 471684 ) on Friday October 01, 2021 @11:58PM (#61852969)

          That's already happening with this drug. From the second linked article [merck.com]:

          At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. Food and Drug Administration (FDA), recruitment into the study is being stopped early due to these positive results. Merck plans to submit an application for Emergency Use Authorization (EUA) to the U.S. FDA as soon as possible based on these findings and plans to submit marketing applications to other regulatory bodies worldwide.

          • Merck plans to submit an application for Emergency Use Authorization (EUA) to the U.S. FDA as soon as possible based on these findings and plans to submit marketing applications to other regulatory bodies worldwide.

            They plan to do it "as soon as possible"? Why is it not possible to submit the application for Emergency Use Authorization right away? Did the FDA fax back something like "Hey Merck dudes, I know you wanted us to look at that emergecy use thingie, but only Janet knows where all the forms are, and she's gonna be in Cancun for maybe another ten days. Sorry, hope there is no EMERGENCY! Haha, jk! But when she gets back you should totally submit that thing, looks sweet! - FDA"

    • Re: (Score:3)

      by nyet ( 19118 )

      I see you have no idea how randomized double blind trials work.

    • After 29 days of follow-up, 53 out of 377 participants who received the placebo were hospitalized with COVID-19, and eight of those participants died.

      And the ethics board?

      From AP: https://apnews.com/article/mer... [apnews.com]

      The results were so strong that an independent group of medical experts monitoring the trial recommended stopping it early.

    • Re:Playing the odds. (Score:4, Insightful)

      by feedayeen ( 1322473 ) on Friday October 01, 2021 @11:51PM (#61852957)
      The recommendation was to end the trials early due to the positive impacts. It wasn't a challenge study where they were infected intentionally so the study objectively saved an estimated 8 lives and avoided 25 hospitalizations. That's a solid win.

      Side note: I find it very strange that nearly a thousand people avoided the most researched vaccines ever created with a insignificant number of side effects discovered with billions of shots given. But within 5 days of testing positive, before any major problems, they jumped at a chance for an experimental medication where they get to be one of the first thousand users. Medical science needs beta testers I guess.

      • So let me get this straight...
        You find is strange that people who make utterly retarded choices about vaccines are also inconsistent, stupid, and hypocritical?

        They're not against medicine. They're just convinced that vaccines are some conspiracy and are poison. The letters RNA scare the shit out of them. JJ vax that isn't RNA? They can't tell the difference. They know nothing. They just flail about blindly. Salt of the earth.

      • I find it very strange

        I don't. Combine anti-establishment with promise of a miracle and you describe a not-insignificant group of people, including those who voluntarily run off and huff down horse anti-parasitics they bought from a feed shop. Add to that the fact that many of these medical studies are actually paid and you will have a lot of willing applicants.

        If we didn't have so many stupid people out there we wouldn't even need a treatment for the virus.

    • And the ethics board?

      What about ethics board? There is no medication that can be legally given except to trial volunteers. These people would have ended up in hospital or would have died without this trial just the same.

    • Re: (Score:2)

      by gweihir ( 88907 )

      And the ethics board?

      What about it? This is how you run such studies. If you have very clear results, you can terminate it early. But that is it. Half of the people in the study receiving "standard care" is not an ethics violation. Yes, sometimes doing Science the correct way does kill people. The important thing is not killing more people than if the study was not done at all. Any halfway competent ethics board understands that.

  • I'll take an mAb, thank you. Well, maybe take them both now that I think about it...

    • Re:50%? (Score:5, Insightful)

      by tempo36 ( 2382592 ) on Friday October 01, 2021 @10:56PM (#61852877)

      While Regeneron has an ~80% risk reduction compared to 50%, it requires far more resources (i.e. infusion room, time, monitoring) and risks (i.e. anaphylaxis) as well as a drug-only cost of ~$1250 per dose. Unless we're planning on setting up infusion rooms for monoclonal antibody therapy in shopping malls, so to speak, it's not nearly as helpful as having a pill that can be dispensed at Walgreens.

      To give you an idea, for a while here in Seattle we had the capacity to treat 1 person PER DAY at one of our major hospitals with Regeneron. Taking all the area hospitals together, we had capacity for about 10 people per day, give or take. Not particularly efficient or convenient when dealing with hundreds of cases a day.

      • To give you an idea, for a while here in Seattle we had the capacity to treat 1 person PER DAY at one of our major hospitals with Regeneron.

        My wife is a nurse and is doing a once-a-week rotation helping provide these monoclonal antibody treatments. They’re handling one person per hour, not per day. But that’s still rather resource intensive.

        On a side note, she was commenting on how much better the typical vaccinated (“breakthrough”) COVID-19 patient looks than the unvaccinated majority.

      • Yes, the mAb treatment protocol is currently cumbersome and it is expensive, but there's a lot of activity in the pipeline to improve this. For example, a company called Sorrento (https://sorrentotherapeutics.com/research/covid-19/covidrops/) is working on a formulation that can be applied by several drops in the nasal passage in 10 minutes with 1/50th the active ingredient needed from the Regeneron product ($1250/50 = $25). Additionally, you don't need to be in the hospital for the treatment.

        It's frust

    • Funny how that is still experimental and the vaccine is approved.

  • Careful (Score:5, Interesting)

    by backslashdot ( 95548 ) on Friday October 01, 2021 @11:46PM (#61852951)

    The smart thing to do is to ensure that whoever gets this drug must be quarantined until they test negative for Covid or there are at least two other equally potent drugs available. The reason being, the virus will mutate to escape this drug. Viruses ALWAYS gain escape mutations. It is a matter of how many point mutations are needed to by the virus to escape susceptibility from the drug. From the name molnupiravir you can instantly tell that this drug is a pyrimidine base analog. Looking at the molecular structure, it is instantly recognizable as a cytidine analog (cytdine is the letter C in RNA). Just from that information, you can guess that the mechanism of this drug, which we used to call NHC, is to mimic cytidine. When the viral polymerase is copying the RNA, instead of using cytidineTP the virus polymerase will try to use molnupiravir (actually a modified form of, but I dont want to complicate things) instead as RNA template. When the virus makes a blunder like that, normally the virus proofreader is supposed to say "what the fuck?" and reject it.. but in this case the proofreader fails. The result is that the virus, when making copies of itself, will (in many circumstances -- I don't want to get into the details) incorporate a G molecule instead of an A and a U instead of C in the RNA code. This means that copies of the virus will have a large number of mutations in it, which is fatal for the virus.

    We know that for certain drugs, like remdesivir, just two mutations can reduce the virus' susceptibility to the drug by a factor of 6. Luckily so far, we've seen that resistance to molnupiravir requires more mutations and even those mutations don't improve the virus chances by much. That said, it's a given fact that meaningful viral resistance WILL occur, and that a strain that is not very susceptible to molnupiravir will emerge. This will occur due to random chance, some coronaviruses will have a version of its RNA proofreader that is different enough that it will be meaningfully less susceptible to the molnupiravir. Although with molnupiravir we have seen that when resistance emerges it severely affects the fitness of the virus, from experience with other pathogens we know that if there is selection pressure, resistant strains will improve in fitness and emerge as the dominant strain. Given time, the virus will evolve enough such that they are just as potent as the older strain. This is what we have seen with HIV for example. AZT is effective against HIV for about 6 months until the resistant version, which is different than the non-resistant version by only one DNA mutation emerges. However three different HIV drugs given at the same time exponentially reduce the chance of viruses escaping because now the virus has to have at least 3 mutations in an exact location. The lesson is that it's dangerous to deploy one drug alone as a treatment because it will allow the virus a chance to evolve against it. What doesn't kill it will make it stronger. Therefore it would be wise to wait until there are at least two more drugs of equal potency that don't use the same mechanism of action.

    TL;DNR: This drug pretends to be an RNA molecule and the virus' proofreader and copier are too dumb to tell the difference. However, there are bound to be strains of the virus with versions of the proofreader that can actually tell the difference. Therefore it is wisest to not give this drug widely until it can be incorporated as part of a triple drug combination. A triple drug combo would require the virus to have too many simultaneous point mutations to be able to escape them --- thereby reducing the chances of a resistance strain emerging.

    • Thanks for taking the trouble to explain that.

      BTW, what's with the Horse references, are there people in the US actually taking veterinary Ivermectin ? In most countries it's got a human version available (not for covid obviously. But you can't really stop off label use by their own will)
      Maybe it's easier to buy veterinary version without a prescription I guess..

      • Re: Careful (Score:5, Funny)

        by backslashdot ( 95548 ) on Saturday October 02, 2021 @12:48AM (#61853021)

        Yes people are taking Ivermectin in the US. I say it's a good thing. Horse-to-human STDs are finally down significantly among Republicans.

      • Yes they do, the sudden spike in demand have made the humane version hard to find (which is a huge FU to the ones that actually needs it) and of course you also have to find a corrupt doctor to prescribe it so people discovered that the version for horses was readily available, cheaper and without the need for a prescription. Never mind that the dosage is completely different and that the inactive ingredients are not tested for human consumption...

  • The REALLY big news (Score:5, Interesting)

    by Miamicanes ( 730264 ) on Saturday October 02, 2021 @12:11AM (#61852979)

    Molnupiravir works against many of the viruses that cause COLDS, too.

    Up to now, the FDA has seized upon any possible flimsy, stupid excuse to deny approval for antiviral meds to treat "colds", throwing roadblock after roadblock at every candidate put before them. Like, "we won't approve a drug that has to be taken before a confident, specific diagnosis is available" (which is a major roadblock, because these drugs HAVE to be taken at the first hint of a dripping nose to really make a difference... if you make someone wait a day or two to get lab results first, the window of opportunity has already closed). Or, "we demand perfect results with NO meaningful adverse effects for ANYONE, even if adverse effects are only found among a small, readily-identifiable group (like women on birth control).

    Thanks to Covid, Molnupiravir is going to be slam-dunk approved... and once it's approved for SOMETHING, US doctors can legally prescribe it for ANYTHING, even if it's something minor like a RSV or rhinovirus infection in an adult.

    It'll probably be 17 years until it's cheap enough to afford without insurance, but if the price is less than the "real" cost of a covid test, we might be able to get almost *any* respiratory infection tentatively diagnosed as 'covid' (with Molnupiravir prescription covered) without insurers DEMANDING a test first, because insurance companies will decide it's more cost-effective to let doctors give Molnupiravir to everyone for anything plausible just to avoid having 1 in 40 patients end up in the ICU for a month.

    Pfizer COULD get greedy, of course... but if they play it smart & make it cheap enough to take for 'nuissance' infections, it could become the biggest blockbuster drug in history.

    • It would be naive russian roulette to use this widespread ..given the pill frenzy caused by Ivermectin and hydroxychloroquine it's a recipe for resistant strains to emerge. We need to wait until there are two more drugs with similar or better performance and then only prescribe it as a triple cocktail (similar to the HIV cocktail ATRIPLA.) I've explained the reasons in my previous comment above titled "Careful." If given to patients as a monotherapy, they must agree to be quarantined until they test negativ

      • Re: The REALLY big news (Score:4, Informative)

        by Miamicanes ( 730264 ) on Saturday October 02, 2021 @01:18AM (#61853047)

        Well, technically, there IS an existing drug candidate that fits the bill for #2 -- Pleconaril. There's no disagreement by anyone that it WORKS, the FDA just got weird about it because it caused 2 or 3 women who were on birth control pills to become pregnant anyway.

        I think there were also concerns that women might be indirectly exposed to Pleconaril via metabolites in seminal fluid (never mind the fact that this happens with almost ANY drug taken by men, and the FDA just started getting crazy about it ~20 years ago & using it as an excuse to deny approval for almost ANY drug not intended to treat a life-threatening condition). So... just add a warning to the label telling people to use condoms for a month after taking it, and the problem is legally solved. Pleconaril becomes safe, and you get a highly-effective 2-drug combo.

        Of course, I'm assuming Molnupiravir IS actually a new drug, and isn't just a tweaked analogue OF Pleconaril altered for the sake of patentability.

        • Re: (Score:2)

          by dynamo ( 6127 )

          Is Pleconaril currently approved? What for?

          • The FDA refused to approve it ~20 years ago:

            * It absolutely worked. If taken at the first sign of infection (ie, feeling a drip forming in your nose, waking up with a scratchy throat, fever, etc) by a virus sensitive to it (I think rhinovirus, picornavirus, and enterovirus were among those confirmed in trials), it pretty much shut its replication down. It was still up to your immune system & apoptosis to kill off the infected cells and clean up the mess, but from YOUR perspective, the infection stopped

    • Pfizer COULD get greedy, of course...

      I think you mean Merck.

      • Pfizer COULD get greedy, of course...

        I think you mean Merck.

        Pfizer is working on a pill too and has reported success in trials.

        • Pfizer is working on a pill too and has reported success in trials.

          Followed by the usual idiots claiming it's just Ivermectin after a different name, so TAKE YOUR IVERMECTIN!

    • Re:The REALLY big news (Score:4, Insightful)

      by Gravis Zero ( 934156 ) on Saturday October 02, 2021 @01:27AM (#61853059)

      Molnupiravir works against many of the viruses that cause COLDS, too.

      Up to now, the FDA has seized upon any possible flimsy, stupid excuse to deny approval for antiviral meds to treat "colds", throwing roadblock after roadblock at every candidate put before them.

      It's more likely that like antibiotics, overuse will render the drug useless. If it was approved for use against cold viruses then every idiot with a sneeze would be taking it. Should it become common knowledge then idiots will start demanding a prescription for it. The result of this is going to be evolution and like covid-19, it will become more of a bastard.

      Bottom line, the problem isn't the drug working or not, it's people abusing the drug because it works.

      • I think you're wildly overestimating the danger.

        Let's start with the most obvious differences between something like rhinovirus and HIV: rhinovirus doesn't destroy your immune system or form a persistent viral reservoir.

        Antiviral meds might enable your body to clear a rhinovirus infection within hours rather than days, but unless you're in really bad shape to begin with, it's GOING to be cleared eventually, regardless. Worst-case, a mutation that gives resistance to the antiviral puts us back to square one,

        • I think you're wildly overestimating the danger.

          And I thin you are underestimating the power of evolution. Why do you think there are so many antibiotic resistant viruses now?

    • Oh good, another drug that will be prescribed incorrectly every time someone sneezes masking an underlying condition or worse.

      The FDA does things for a reason, but I guess you've learnt nothing from the our steadily failing anti-biotics overuse, or the opioid epidemic.

      Ask your doctor if X is right for you. He will of course say yes because he doesn't give a fuck as long as the gets paid.

      • If they wanted molnupiravir to be a universal hammer, they should have shortened the name to, say, Mjolnir.
    • Wait a second... In the UK, the government hands out cheap DIY Covid tests to everyone. Takes 15 minutes. Bit uncomfortable because you have to stick a pointy thing into your throat and nose. I assume these tests are cheap, because they are handed out to anyone.

      It's quite possible that this medication is cheaper than a proper expensive + more reliable Covid test. In that case the recommendation to people would be: Have the cheap test at home (they are delivered in packs of seven, so no problem). At the s

  • The US government made an advance purchase of 1.7m doses of the drug at a cost of $1.2bn, and the company said on Friday it would use a “tiered pricing approach” to reflect countries’ ability to pay for the drug.

    https://www.theguardian.com/wo... [theguardian.com]

  • I don't trust you one bit, ever since you paid Elsevier to create four fake magazines aimed at doctors to get them to prescribe the wrong medication to patients with fake studies, just so you could make money, literally figuratively walking over dead bodies.

    And [Mjolnirpredatorvirus] is an exceptionally stupid name for a pill. No it doesn't work better because it is hard to read or pronounce. It only makes it look like that's what you want people to think. And there's that old psychopath behavior pattern ag

  • But, it's less effective than monoclonal antibodies, just cheaper and easier to administer. Easier to administer means more profit for hospitals, even if it's less effective.

    • Easier to administer means it can be given to many more people. 50% effective across 10,000 patients is better than 100% effective given to 1000 patients.

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