Talk:Molnupiravir/Archive 1

Covid19
Si este fármaco previene el covid es una buena señal para todos en este planeta Gregori milano (talk) 06:48, 6 December 2020 (UTC)


 * This drug does what Ivermectin does - but Ivermectin is patent free so Big Pharma need to quash it to make money from their new patent. — Preceding unsigned comment added by 49.178.38.222 (talk) 01:30, 2 October 2021 (UTC)
 * Ivermectin and molnupiravir were/are both developed by Merck. Molnupiravir has not made them a cent (yet) as it has not been sold to anyone. The use of Ivermectin as a Covid therapy is controversial to say the least but if used would still make money for its manufacturer, as is only reasonable. Mike Turnbull (talk) 21:47, 2 October 2021 (UTC)
 * Ivermectin inhibits viral protein import into the nucleus as a broad-spectrum inhibitor of importin α/β nuclear import, whereas Molnupiravir is designed to cause massive mutation in RNA of down stream copies. the statement of "Molnupiravir does what Ivermectin does" is used too broadly or a mistatement, as the mechanism of antiviral action are completely separate mechanisms. — Preceding unsigned comment added by 2605:A601:A0C6:1200:2D7A:3351:1B44:CC21 (talk) 07:00, 9 October 2021 (UTC)
 * Moreover, Ivermectin is not considered effective against SARS-CoV-2 in-vivo at safe dosage level... — Paleo  Neonate  – 14:54, 12 October 2021 (UTC)

IUPAC name
Does the term "isobutyrate" really have a place in an IUPAC name? Shouldn't it be "methylpropanoate"? 92.40.178.227 (talk) 15:54, 1 October 2021 (UTC)
 * IUPAC names can be a bit of a mess. The article had one (from Pubchem) that was computer-program generated. I've replaced it with an expert-validated version from Chemspider, which also has the advantage of making the relationship to cytidine more obvious. Mike Turnbull (talk) 21:36, 2 October 2021 (UTC)

Seasons
The phrase "in the spring of 2020." is imprecise. The northern and southern hemispheres have the season of spring at opposite different times. — Preceding unsigned comment added by 151.210.155.254 (talk • contribs) 2 October 2021 (UTC)
 * Confirmed to be fixed since then, — Paleo Neonate  – 14:49, 12 October 2021 (UTC)

"See also" section
Per MOS:ALSO I have just removed a large number of drug names from the "See also" section of this article, leaving only those which have a structural resemblance to molnupiravir. I can see no justification for linking miscellaneous drugs such as amantadine which have no clear relationship to it (and one where the MOS specifically prohibits redlinks). Mike Turnbull (talk) 12:06, 4 October 2021 (UTC)
 * I'm not really convinced that this article needs any other drugs in its "See also" section, given that it has the template included at the bottom, which has a comprehensive list. Mike Turnbull (talk) 15:45, 4 October 2021 (UTC)
 * Agreed. Those non-similar drugs (in the technical definition of "similar") should be removed. — Shibboleth ink  (♔ ♕) 17:17, 4 October 2021 (UTC)

Registry number
Another registry number is 2492423-29-5 from https://chem.nlm.nih.gov/chemidplus/rn/2492423-29-5, so if anyone has access to the real CAS, please check which CAS number is the best. Graeme Bartlett (talk) 00:40, 13 October 2021 (UTC)
 * My guess (and it's only a guess) is that the two CAS numbers are both valid and represent the two tautomers: exocyclic -NHOH and exocyclic =NOH. One drawback for CAS is that they have to index what people publish and only much later realise compounds are identical via their InChI. If you Google either 2349386-89-4 or the number you cite, you'll see plenty of hits for both — and both are mentioned as synonyms on Pubchem. For the present, I think we can stick to the earlier number, which is the one CAS will likely adopt long-term. Mike Turnbull (talk) 11:12, 13 October 2021 (UTC)

Cancer and birth defects claims
Canavalia, I see that you have been edit-warring today to get a statement in the article about an in vitro test that suggests a risk for cancer and birth defects. It is generally a bad idea to make such a claim based on cell cultures. The results seen in a single in vitro test are rarely reproducible or sustained upon further investigation. We normally exclude such sources entirely. Why do you think we should make an exception for this? WhatamIdoing (talk) 19:12, 15 October 2021 (UTC)
 * I have removed that.
 * Single in-vitro results highly oppose WP:MEDRS. --Julius Senegal (talk) 20:35, 15 October 2021 (UTC)
 * We have a primary paper with a claim and a primary response, but no better source that mentions both in context was proposed yet. As others noted, there's a large gap between in-vitro and in-vivo, so let's at least wait for better sources.  — Paleo  Neonate  – 23:36, 18 October 2021 (UTC)

Etymology of the name
Can someone breakdown the provided name "molnupiravir"? And its origination? -- 64.229.90.53 (talk) 13:24, 4 November 2021 (UTC)
 * "-vir" -- antiviral drug
 * The rest is explained in the history section of the article, based, apparently, on Thor's hammer Mjölnir. Mike Turnbull (talk) 13:41, 4 November 2021 (UTC)
 * "molnupira" is all just Thor's Hammer? I can see the "molnu" part, but there's a p stuck there. -- 64.229.90.53 (talk) 16:08, 4 November 2021 (UTC)

Marketing and expected sales
I plan to include a paraphrase of the following text:, from this source. That Merck did this estimate is a verifiable fact that complies with WP:Crystal, particularly this part:. I put this here to discuss because a similar edit that I tried has been reverted twice, invoking a violation of WP: Crystal. Forich (talk) 00:32, 9 November 2021 (UTC)
 * Is there an independent assessment? And was this prediction made before the results of other antiviral trials appeared? Seems like the sort of thing Merck would like to announce - coincidentally it's for good for their share price. Alexbrn (talk) 07:10, 9 November 2021 (UTC)

Concerns raised over mutation of SARS-CoV-2
In this diff added on 7 November, added two external links that seem to me to fail WP:MEDRS. Should they be reverted or are they OK because they are not used to support information in the body of the article? The links both point to alleged "dangers" of the drug. Mike Turnbull (talk) 13:49, 9 November 2021 (UTC)
 * Unreliable, so removed. Alexbrn (talk) 13:55, 9 November 2021 (UTC)

Hi, I am not a regular editor nor qualified on pharmaceuticals.

Please reconsider decision to remove links to series of articles by William_A._Haseltine. As described by his wikpedia biography he is not "unreliable" but rather "authoritative" and "expert".

His series of warnings on Molnupiravir seem entirely consistent with those expressed more generally concerning dangers from antivirals driving evolution of escape Variants of High Consequence in authoritative expert advice to UK Sage:

[]

That advice was endorsed in Sage 94 minutes ]

Also accurately summarized by Haseltine []

Those links should also be included in a full section on discussion of the issue in the article. — Preceding unsigned comment added by 2001:8003:D840:DA01:D653:B00F:D88:2DD (talk) 00:34, 10 November 2021 (UTC)

PS Another important link for a full section discussing controversy regarding Molnupiravir would be

This quotes others agreeing and disagreeing. For what it is worth, in my opinion the disagreements from Merck sources seems quite specious. Selection would be driven by pressure to transmit to others not by a "bias" in the mutations and it is quite notorious that in real world people often do not take the full courses required in controlled trials which is the basis for evolution of resistant pathogens. " In patients who completed the 5-day course of the drug, Hazuda says, “we don’t see any infectious virus”—let alone mutated variants." That sounds like marketing not science. — Preceding unsigned comment added by 144.131.41.182 (talk) 00:53, 10 November 2021 (UTC)
 * Please see WP:MEDRS for Wikipedia's medical sourcing guidelines. Alexbrn (talk) 02:40, 10 November 2021 (UTC)

I did review that content guideline before posting and noted the prominent paragraph at the top which says:

"It is a generally accepted standard that editors should attempt to follow, though it is best treated with common sense, and occasional exceptions may apply."

Please see the link provided from there to "common sense"

In my view it is a violation of "common sense" to not include a section on the medical controversy about the evolutionary virology consequences of authorizing a mutagenic antiviral in an encyclopediac article on Molnupirarir.

I have provided adequate references for you to understand the context and for use when adding a suitable section on the controversy initiated by William Haseltine (or including it in the existing equally "unreliable" section 3.1 "Alleged Safety Concern").

Please ask other editors to review this issue and these links. 144.131.41.182 (talk) 11:00, 10 November 2021 (UTC)
 * There is no "medical controversy". There is only a single person concerned about "similar experimental drugs", and only in a different context (animal, amount,...). --Julius Senegal (talk) 11:45, 10 November 2021 (UTC)

There is a "medical (and public health policy) controversy and the context is approval for widespread human use.

Simply google "Monupiravir mutagenic" and "Monupiravir dangerous" and check the long list of items. A controversy does not cease to be a controversy by presenting only the Merck press release. 144.131.41.182 (talk) 13:54, 10 November 2021 (UTC)
 * Wikipedia is based on reliable sources, not any old dross on the interwebz. Alexbrn (talk) 14:25, 10 November 2021 (UTC)
 * Actually we had reliable (but not WP:secondary) sources in this diff which covered both the suggestion of mutagenicity and Merck's rebuttal. Both were removed, correctly in my opinion, because although peer-reviewed these primary sources were included before the compound was accepted into use by UK and other regulators, who will have seen and considered much more data than we have access to. Wikipedia can wait until matters become much clearer before modifying the article in this regard. Mike Turnbull (talk) 15:36, 10 November 2021 (UTC)
 * Yes, and such primary research is by definition unreliable for Wikipedia's purposes. Alexbrn (talk) 05:16, 11 November 2021 (UTC)

I did not know about the diff with reliable primary sources that was removed - thanks for drawing attention to it.

The UK's MHRA had not released a Public Assessment Report (PAR) at the time it announced its decision so naturally authoritative medical secondary sources will wait until it does so before responding to it with their own analyses.

But it is clear there is already now a controversy about the UK MHRA's decision to approve a mutagenic anti-viral despite UK SAGE warnings about the dangers from promoting evolution of worse variants. Wikipedia has no business taking a position on that controversy whether it waits until matters become much clearer or not. Nobody is waiting for Wikipedia's opinion. Controversies are regularly mentioned in Wikipedia and are usually "not clear" almost by definition. The article already has a section 3.1 on "Alleged Safety Concern". It is common sense to mention the far more significant concern about promoting evolution of more virulent escape variants. Deliberately choosing to exclude mentions of it is intentional enforcement of a specific point of view.

The dismissive comment about "any old dross from the interwebz" from the editor who removed links to material published in a major publication by William A. Haseltine suggests a cavalier level of arrogance that requires escalation to serious review by other editors.

I recall that there is a process for this. If the editor whose decision I am disputing has not already initiated this process, could somebody else please confirm they have done so. As mentioned I am not a regular editor and am not familiar with the process. 144.131.41.182 (talk) 03:45, 11 November 2021 (UTC)
 * Yes, you lack basic understanding of Wikipedia's sourcing standards and, rather than attempting to learn, you're pushing your view. If in doubt, maybe ask at WT:COVID for further input. Alexbrn (talk) 05:16, 11 November 2021 (UTC)

Ok it will take a while to become sufficiently familiar with the process but I will attempt to learn.

Have started from WT:COVID and quickly run into the XKCD wikipedia problem

My current guess is that the problem I am disputing concerning exclusion of information about an important current controversy arises because of some overeaction to a phenomena that would be particularly likely to affect COVID-19 articles

I will wait to see whether other editors are more open to the view I am pushing while spending the necessary time exploring from WT:COVID and understanding the dispute resolution process.

My current impression is that I should then continue to argue the point here and the next step would be WP:3. Please advise if I should be looking elsewhere 2001:8003:D840:DA01:D653:B00F:D88:2DD (talk) 12:39, 11 November 2021 (UTC)
 * WP:3 is inappropriate because there are already several people involved. The standard for medical sourcing on wikipedia is exceptionally high (WP:MEDRS). Alexbrn (talk) 16:30, 11 November 2021 (UTC)

I have now created an account and become sufficiently familiar with wikipedia process to decide that I simply do not have time to argue further with Alexbrn.

Whatever the merits of previous decisions I suggest that suppression of the following information from NIH treatment guidelines should be actively fought by anybody that does have the time. I don't so I am posting the excerpts here for others to work out how to appropriately include them in the article.

https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-therapies-for-high-risk-nonhospitalized-patients/

The COVID-19 Treatment Guidelines Panel's Statement on Therapies for High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19

Last Updated: December 30, 2021

...

Molnupiravir has potent antiviral activity against SARS-CoV-2.4 As a mutagenic ribonucleoside antiviral agent, there is a theoretical risk that molnupiravir will be metabolized by the human host cell and incorporated into the host DNA, leading to mutations. Molnupiravir has been evaluated in 2 in vivo rodent mutagenicity assays. One study produced results that were equivocal; in the other study, there was no evidence for mutagenicity. The FDA concluded that, based on the available genotoxicity data and the 5-day duration of treatment, molnupiravir has a low risk for genotoxicity.6 In addition, there have been concerns about the potential effects of molnupiravir on SARS-CoV-2 mutation rates; the FDA is requiring the manufacturer to establish a process to monitor genomic databases for the emergence of SARS-CoV-2 variants.

...

[Relevant list of "above options" alternatives to Molnupiravir omitted for brevity but should be summarized]

Molnupiravir 800 mg orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥18 years ONLY when none of the above options can be used (CIIa).

The FDA EUA states that molnupiravir is not recommended for use in pregnant patients due to concerns about the instances of fetal toxicity observed during animal studies. However, when other therapies are not available, pregnant people with COVID-19 who are at high risk of progressing to severe disease may reasonably choose molnupiravir therapy after being fully informed of the risks, particularly those who are beyond the time of embryogenesis (i.e., >10 weeks’ gestation). The prescribing clinician should document that a discussion of the risks and benefits occurred and that the patient chose this therapy. There are no data on the use of molnupiravir in patients who have received COVID-19 vaccines, and the risk-to-benefit ratio is likely to be less favorable because of the lower efficacy of this drug.

Rationale

Multiple therapeutic agents are now available for nonhospitalized patients with mild to moderate COVID-19 who are at high risk of disease progression. The Panel favors the use of ritonavir-boosted nirmatrelvir (Paxlovid) in most high-risk, nonhospitalized patients with mild to moderate COVID-19. If ritonavir-boosted nirmatrelvir (Paxlovid) is not available or cannot be used because of drug interactions, then the Panel recommends using sotrovimab. If sotrovimab is not available, then the Panel recommends using remdesivir. Molnupiravir should only be administered when the other 3 options are either not available or cannot be used.

There are currently no clinical trial data that compare the clinical efficacy of these 4 therapies, and there are no data on the use of combinations of antiviral agents and/or anti-SARS-CoV-2 mAbs for the treatment of COVID-19. The rationale for the Panel’s recommendations is discussed below.

...

Molnupiravir

In the MOVe-OUT trial, molnupiravir reduced the rate of hospitalization or death by 30% compared to placebo.6 Even though the different treatment options have not been directly compared in clinical trials, the Panel recommends using molnupiravir only when ritonavir-boosted nirmatrelvir (Paxlovid), sotrovimab, and remdesivir are not available or cannot be given, because molnupiravir has lower efficacy than the other options.

Molnupiravir is expected to be active against the Omicron VOC, although in vitro and in vivo data are currently limited.

...

Additional Considerations When Using Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Molnupiravir

...

Molnupiravir

Patients should complete the 5-day treatment course of molnupiravir. It is unknown whether a shorter course is less effective or whether a shorter course is associated with the emergence of molnupiravir-resistant mutations. Patients of childbearing potential should be counseled about abstaining from sex or using reliable contraception for the duration of therapy and for up to 4 days after receiving molnupiravir. Reproductive toxicity has been reported in animal studies of molnupiravir, and molnupiravir may be mutagenic during pregnancy. Men of reproductive potential who are sexually active with individuals of childbearing potential should abstain from sex or use a reliable method of contraception for the duration of treatment and for at least 3 months after the last dose of molnupiravir. The FDA EUA states that molnupiravir is not recommended for use in pregnant patients due to concerns about fetal toxicity that are based on data from animal studies. However, when preferred therapies are not available, pregnant people who are at high risk of progressing to severe disease may reasonably choose molnupiravir therapy after being fully informed of the risks, particularly those who are beyond the time of embryogenesis (i.e., >10 weeks’ gestation). The prescribing clinician should document that a discussion of the risks and benefits occurred and that the patient chose this therapy. Based on the lack of data on the use of molnupiravir in lactating people and the potential for adverse effects in the infant from molnupiravir exposure, the current recommendation is to avoid feeding an infant breast milk during molnupiravir treatment and for 4 days after the final dose. Pumping and discarding breast milk to maintain supply during this time is recommended. There are no data available on the use of molnupiravir in children aged <18 years. Molnupiravir is not authorized for use in children aged <18 years due to potential effects on bone and cartilage growth. Based on in vitro studies, neither molnupiravir nor its active metabolite NHC are inhibitors or inducers of major drug-metabolizing enzymes or inhibitors of major drug transporters. According to the EUA, no drug-drug interactions have been identified for molnupiravir. The most common adverse effects of molnupiravir are diarrhea, nausea, and dizziness.

...

Clinical Trial Data

...

Molnupiravir

MOVe-OUT was a multinational, Phase 3, randomized trial that compared the use of molnupiravir 800 mg administered orally every 12 hours for 5 days to placebo. The participants were nonhospitalized, unvaccinated, nonpregnant adults with mild to moderate COVID-19 who were at high risk of clinical progression to severe COVID-19 and who were within 5 days of symptom onset.11 The primary composite outcome was all-cause hospitalizations (defined as hospital stays that lasted >24 hours) and deaths by Day 29.

In an interim analysis that included 50% of the target accrual population, hospitalization or death occurred in 28 of 385 participants (7.3%) in the molnupiravir arm and in 53 of 377 participants (14.1%) in the placebo arm by Day 29 (adjusted difference of -6.8%; 95% CI, -11.3% to -2.4%; P = 0.001).11

The final analysis included 1,433 participants; the median age was 43 years (with 17% aged >60 years). Forty-nine percent of the participants were men, 57% were White, 50% were Hispanic/Latino, and 5% were Black or African American. Among the participants, 74% had a body mass index ≥30 and 16% had diabetes. The time from COVID-19 symptom onset to randomization was ≤3 days in 48% of participants.

By Day 29, hospitalizations or deaths had occurred in 48 of 709 participants (6.8%) in the molnupiravir arm and in 68 of 699 participants (9.7%) in the placebo arm (30% relative risk reduction; -3.0% adjusted difference; 95% CI, -5.9% to -0.1%; P = 0.0218).6 There was 1 death in the molnupiravir arm, and there were 9 deaths in the placebo arm. There were no significant differences between the arms in the proportion of participants who experienced adverse events or serious adverse events.

The difference in the efficacy of molnupiravir that was observed between participants in the interim analysis and those enrolled after the interim analysis has not been fully explained.

[PS highlighting accidental while intending to simply cut and paste without any style.] ArthurD8 (talk) 14:19, 5 January 2022 (UTC)

Science wrote about this discussion. It's on ongoing discussion that could turn out to be very important. If Science presents the facts as we know them now, why can't Wikipedia? The FDA advisory panel had no single expert on evolution on it. This drug is entirely new, there is no drug with a similar mechanism of action on the market. There is obviously no trial on this issue yet. All that we have is "expert opinion", and that's clearly listed by WP:MEDRS and WP:MEDRS also treats Science as one of the most respectable sources. It's not a research article, but not any nonsense gets written about in Science. Science treats this topic as it is, an interesting question, a discussion between experts. Trials obviously do not include very low doses of a drug, for most drugs this makes no sense. But for this one it does, because this drug induces mutations. This discussion is not about a single person, but about one field of biology (evolutionary biology, genetics) versus medicine and pharmacology experts. Here is a preprint by an entirely different group of biologists, just rejected from Nature, that makes the same argument: https://virological.org/t/mutagenic-antivirals-the-evolutionary-risk-of-low-doses/768 This discussion is not one made by a single reseaercher and the next few days will make this more and more obvious, as soon as the evolutionary biology community gets to know the issue. Mhaeussl (talk) 10:46, 1 December 2021 (UTC)
 * You may well be correct,, that possibly unwanted side-effects of the mutagenic mechanism of action will become clearer later but until then this is a classic example of WP:Crystal, I think. Wikipedia has to be a lagging reporter in controversial areas, especially medical ones. Meanwhile, the mechanism of action of this drug is explained quite clearly in the article. Mike Turnbull (talk) 11:06, 1 December 2021 (UTC)
 * I'l going to re-title this section if that's OK. I think 'External links' isn't clear. - Pointillist (talk) 12:04, 11 December 2021 (UTC)
 * I'm not sure if I understand your intention correctly, but a final "External links" section is absolutely standard in Wikipedia articles. See WP:EL. Mike Turnbull (talk) 13:08, 11 December 2021 (UTC)
 * I mean the talk page section, not the main page section. Agreed that in a sense every talk page debate about an external link is inherently about whether it is on topic, authoritative and independent. Aguably every such discussion could be headed 'external link(s)', but that's not the way talk page sections are usually titled. It's more helpful if the section title indicates the point at issue, isn't it? - Pointillist (talk) 23:05, 11 December 2021 (UTC) (updating a post at 22:53, 11 December 2021 UTC)
 * Ah, now I see what you mean . When I created this Talk Page section I did indeed call it "External Links" because that was the part of the article that I was concerned about at the time. Now the discussion has moved on a bit, I certainly don't mind that you changed it. Mike Turnbull (talk) 12:58, 12 December 2021 (UTC)

I just added:

"However, there is concern that molnupiravir may have caused the emergence of the omicron variant, and should therefor be withdrawn from use. "

and:

"There are features of the omicron variant that suggest it arose in a person in South Africa who received molnupiravir. "

These were immediately reverted by User:Alexbrn with the comment "Trim unreliable, would need WP:MEDRS" (whatever that means). He also indiscriminately removed a phrase I had added about the tautomers. The source I gave is an article by the distinguished virologist William A. Haseltine. I have had trouble with Alexbrn in the past and with others. They say you need "reliable medical references", but if you give a reliable medical reference (Haseltine gives references), then they say that it's a primary source, so it's not acceptable. So I also gave a secondary source (New Scientist), but of course that didn't satisfy him. I really think that either the rules of Wikipedia are bad, or they're being applied in a bad way, preventing important information from being put in articles. Eric Kvaalen (talk) 10:48, 18 December 2021 (UTC)


 * WP:FORBESCON seriously? Please don't. You are now aware of the WP:Discretionary sanctions in effect for this topic. In case you are still confused, the relevant standard for biomedical claims is WP:MEDRS. Alexbrn (talk) 11:00, 18 December 2021 (UTC)


 * Alex, you deleted my latest comment, which is against Wikipedia policy (Talk page guidelines). But at least you saw what I wrote. Eric Kvaalen (talk) 07:59, 21 December 2021 (UTC)

French Regulators Refuse Authorization and NIH recommends only use as a last resort
Proposed new section. Leaving it to others to figure out how to edit it in.

https://www.has-sante.fr/jcms/p_3304161/fr/covid-19-deux-nouveaux-traitements-evalues-par-la-has

Prominent addition should be made at start of article together with other "contraindications" and together with following excerpt from NIH recommendation to only use as a last resort when nothing else available (quoted more fully above):

https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-therapies-for-high-risk-nonhospitalized-patients/

The COVID-19 Treatment Guidelines Panel's Statement on Therapies for High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19

Last Updated: December 30, 2021

"Multiple therapeutic agents are now available for nonhospitalized patients with mild to moderate COVID-19 who are at high risk of disease progression. The Panel favors the use of ritonavir-boosted nirmatrelvir (Paxlovid) in most high-risk, nonhospitalized patients with mild to moderate COVID-19. If ritonavir-boosted nirmatrelvir (Paxlovid) is not available or cannot be used because of drug interactions, then the Panel recommends using sotrovimab. If sotrovimab is not available, then the Panel recommends using remdesivir. Molnupiravir should only be administered when the other 3 options are either not available or cannot be used."

(emphasis added)

Here's the google translation of French announcement:

https://www.has-sante.fr/jcms/p_3304161/fr/covid-19-deux-nouveaux-traitements-evalues-par-la-has

The HAS does not authorize early access to Lagevrio® as a curative treatment for mild and moderate forms of Covid-19

Molnupiravir, Lagevrio®, from the MSD France laboratory is an antiviral curative treatment, that is to say which acts on the virus to prevent it from replicating and thus limit or even stop the infection. Its use is therefore targeted on patients infected with SARS-CoV-2, and the laboratory is requesting its early access in "treatment of mild to moderate forms of coronavirus disease 2019 (Covid-19) in adults with a test of positive diagnosis for SARS-CoV-2 and who have at least one risk factor for developing a severe form of the disease”.

In its opinion, the ANSM concluded, considering the current epidemic context of the 5th wave of Covid-19 and the potential impact of the Omicron variant on existing therapeutic options, that the efficacy and safety of this drug were presumed in a restricted indication compared to that claimed by the laboratory: "treatment of Covid-19 in the event of impossibility of recourse to monoclonal antibodies in adults not requiring oxygen therapy, and being at high risk of evolution towards a form disease, namely the following populations as defined by the ANRS-Emerging Infectious Diseases: patients aged 80 and over, patients with an immune deficiency linked to a pathology or treatment[2] as well as patients at risk of complications[3]. However, the ANSM indicates that there are still questions about this antiviral with its mechanism of action of lethal mutagenicity on the virus and about the robustness of the MOVe-OUT study for which the laboratory must provide additional data.

Based on these elements and on the basis of the opinion formulated by the Transparency Commission (CT), HAS considers that Lagevrio® does not meet the necessary criteria to obtain an early access authorization. In particular, it considers that the presumption of innovation cannot be upheld.

Indeed, the efficacy results put forward by the laboratory are less good than those of the available treatments: 30% reduction in the risk of progression to the severe form of Covid-19 (according to the MOVe-OUT study) while the The efficacy for casirivimab-imdevimab monoclonal antibodies is approximately 80% on this same criterion.

In addition, HAS notes a significant discrepancy between the data collected over the first period of the study (interim analysis, approximately 50% efficacy) and those collected over the second period (difference between the interim analysis and the final, no efficiency). However, the data from this second period, whose characteristics are closer to current epidemiology in France, mainly represented by the Delta variant, are against Lagevrio®.

In addition, the impact of treatment on viral load negativity (reducing the presence of the virus until it becomes undetectable) has not been demonstrated.

The HAS insists on the fact that access to Lagevrio® in the community would risk inducing a loss of opportunity for patients, who would not be treated by a more effective treatment, Ronapreve®. And it is taking advantage of this decision to encourage easier access to Ronapreve® as a cure throughout the territory during this 5th wave linked to the delta variant. In addition, it would like clinical trials to be set up to evaluate Lagevrio® in combination with another molecule in order to be able to assess the possible place that this drug could have in the curative treatments recommended against Covid-19.

ArthurD8 (talk) 14:26, 8 February 2022 (UTC)

See also (for early covid-19 treatment): Pfizer Paxlovid.
https://en.wikipedia.org/wiki/PF-07321332

It is for early covid-19 treatment too. Like Merck Molnupiravir.

And then there is some promising clinical studies for a very old drug, Fluvoxamine.

https://en.wikipedia.org/wiki/Fluvoxamine

--91.159.191.219 (talk) 21:58, 14 November 2021 (UTC)--91.159.191.219 (talk) 21:58, 14 November 2021 (UTC)
 * In medicine-related articles, the Wikipedia manual of style (specifically WP:MEDSECTIONS) says Avoid the See also section when possible; prefer wikilinks in the main article and navigation templates at the end. This is to avoid that section becoming a long list of topics which might be of relevance but for most readers will not be. Specifically in this case, Paxclovid is not related to molnupiravir either structurally of by mechanism of action; it just happens to be a candidate for use against COVID-19. Mike Turnbull (talk) 11:57, 15 November 2021 (UTC)

Phase III results on NEJM: not WP:MEDRS?
In, the efficacy reported in the phase III results published on the New England Journal of Medicine (NEJM) was removed because the content was considered unreliable. Why is it so? The NEJM is a core medical journal, and WP:MEDRS says If conclusions are worth mentioning (such as large randomized clinical trials with surprising results), they should be described appropriately as from a single study which I believe is the case. --Fernando Trebien (talk) 15:12, 27 December 2021 (UTC)
 * I would support including this passage, for this same reason. I find it to be encyclopedic, and indeed the surprising efficacy of this drug in that trial has been covered by many secondary non-MEDRS RSes even in the few days since its publication. — Shibboleth ink  (♔ ♕) 15:26, 27 December 2021 (UTC)
 * It is a primary source. It is written by authors who directly participated in the research and documented their personal experience. WP:MEDDEF, WP:MEDFAQ. Also, please be advised that the FDA fact sheet is published by and copyright Merck. --Whywhenwhohow (talk) 04:58, 28 December 2021 (UTC)
 * Then the problem is to determine in which situations WP:MEDRS would allow a primary source. WP:MEDRS clearly does not prohibit them completely, just recommends caution when supporting claims and grants a preference to secondary sources. In WP:MEDASSESS we have "clinical practice guidelines" and "critically-appraised individual articles" as kinds of "filtered information", I think both fit the approval given by the FDA. Some time ago, I tried to WP:MEDRS adding a link to WP:MEDFAQ, but it was reverted because WP:MEDFAQ it is unfinished. In any case, WP:MEDFAQ allows primary sources for research that had a significant impact, which it describes as "continued and substantial coverage". --Fernando Trebien (talk) 11:02, 28 December 2021 (UTC)
 * MEDRS has a notion of an "ideal" source. That ideal is about writing about subjects with a substantial base of research (COVID counts) going back for years (COVID doesn't really count).  In this ideal, you use review articles, practice guidelines, and textbooks from the last five years.
 * MEDRS also says in WP:MEDPRI that primary sources might sometimes be worth using, occasionally, at least temporarily, until the academic publication cycle has had an opportunity to comment on that research. If it does, then we "upgrade" the article to cite the MEDRS ideal source instead.  If it doesn't comment on a primary source after a "reasonable" amount of time, then we guessed wrong, and that information should be removed.
 * For new or poorly researched medical subjects, MEDRS and its "ideal" are not necessarily practical. MEDRS makes a very poor substitute for the policy on Balancing aspects.  Step one should probably be to figure out what kind of content would ideally be in an article like this.  Manual of Style/Medicine-related articles may be a useful starting point, but don't forget your common sense.  From there, try to use MEDRS's ideal for as much as you can, and fill in any important blanks from the best non-ideal sources you can get.  I would not recommend letting the perfect be the enemy of the good in a COVID article. WhatamIdoing (talk) 07:15, 29 December 2021 (UTC)
 * So, in this article, do you agree that it should be ok to mention the efficacy result in the "Medical uses" section citing the only one available with such data, which is a primary source, as long as it is presented as phase III study data reported by the manufacturer? --Fernando Trebien (talk) 15:48, 29 December 2021 (UTC)
 * I'm not at all convinced there is any reason to use the primary study as a source. The relevant data about reduction in hospitalisations and deaths is already available from government websites. And we should not be using a press release from Merck at all. Although this is 'new' it is also so widely covered that we are not struggling for reliable sources to talk about it. -- Colin°Talk 16:19, 29 December 2021 (UTC)