Molnupiravir for COVID-19: real-time analysis of all 21 studies

Effectiveness of Molnupiravir in High Risk Patients: a Propensity Score Matched Analysis

Najjar-Debbiny et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac781

PSM retrospective 2,661 molnupiravir patients in Israel, showing lower mortality and severe COVID-19, without statistical significance. Significant benefit was seen in some subgroups, and significant harm was seen in the <75 subgroup.

risk of death, 19.0% lower, HR 0.81, p = 0.48, treatment 22 of 2,661 (0.8%), control 27 of 2,661 (1.0%), NNT 532, propensity score matching.

risk of progression, 17.0% lower, HR 0.83, p = 0.34, treatment 50 of 2,661 (1.9%), control 60 of 2,661 (2.3%), NNT 266, severe COVID-19 or COVID-19 mortality, propensity score matching.

risk of severe case, 25.0% lower, HR 0.75, p = 0.15, treatment 43 of 2,661 (1.6%), control 57 of 2,661 (2.1%), NNT 190, propensity score matching.

Najjar-Debbiny et al., 20 Sep 2022, retrospective, Israel, peer-reviewed, 8 authors, study period January 2022 - February 2022.

Outcome of lung transplant recipients infected with SARS-CoV-2/Omicron/B.1.1.529: a Nationwide German study

Kneidinger et al., Infection, doi:10.1007/s15010-022-01914-8

Retrospective 218 COVID+ lung transplant patients in Germany, showing no significant difference in severe cases with early molnupiravir use.

risk of severe case, 15.1% higher, RR 1.15, p = 0.71, treatment 8 of 46 (17.4%), control 26 of 172 (15.1%).

Kneidinger et al., 9 Sep 2022, retrospective, Germany, peer-reviewed, 11 authors, study period 1 January, 2022 - 20 March, 2022, lung transplant patients.

Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13,694 patients

Lawrence et al., Research Square, doi:10.21203/rs.3.rs-1913200/v1 (Preprint) (meta analysis)

Meta analysis of molnupiravir trials showing 12 registered RCTs in India with only one presented at a conference, and two issuing press releases suggesting failure. Authors find that ~90% of the global data on molnupiravir has not been published. Authors also highlight issues with trials including the unexplained doubling in size and delayed presentation of PANORAMIC.

See also: [twitter.com].

1. twitter.com, https://twitter.com/JackMLawrence/status/1558942614140993537.

Lawrence et al., 2 Aug 2022, preprint, 3 authors.

SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model

Lieber et al., Nature Communications, doi:10.1038/s41467-022-32045-1

Roborovski dwarf hamster and in vitro study finding molnupiravir efficacy varied significantly by SARS-CoV-2 variant in the hamster model, in contrast to no significant difference seen in cultured cells and human organoids. Efficacy for omicron in the hamster model varied significantly based on biological sex.

Lieber et al., 29 Jul 2022, USA, peer-reviewed, 15 authors.

A Randomised-Controlled Phase 2 trial of Molnupiravir in Unvaccinated and Vaccinated Individuals with Early SARS-CoV-2

Khoo et al., medRxiv, doi:10.1101/2022.07.20.22277797 (Preprint)

RCT 90 molnupiravir and 90 placebo patients, showing faster viral clearance with treatment, not reaching the pre-defined threshold for superiority and recommendation as a candidate for large scale evaluation. The supplementary figures and tables mentioned are not currently available.

risk of oxygen therapy, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 90 (0.0%), control 1 of 90 (1.1%), NNT 90, relative risk is not 0 because of continuity correction due to zero events.

risk of hospitalization, 88.9% lower, RR 0.11, p = 0.12, treatment 0 of 90 (0.0%), control 4 of 90 (4.4%), NNT 22, relative risk is not 0 because of continuity correction due to zero events.

risk of no viral clearance, 23.1% lower, HR 0.77, p = 0.07, treatment 90, control 90, inverted to make RR<1 favor treatment, primary outcome.

Khoo et al., 24 Jul 2022, Double Blind Randomized Controlled Trial, placebo-controlled, United Kingdom, preprint, 36 authors, study period 8 September, 2020 - 16 March, 2022, average treatment delay 3.3 days, trial NCT04746183 (history) (AGILE CST-2).

Real-world experience with molnupiravir during the period of SARS-CoV-2 Omicron variant dominance

Flisiak et al., Pharmacological Reports, doi:10.1007/s43440-022-00408-6 (preprint 7/6/2022)

Retrospective 590 patients in Poland, 203 treated with mulnupiravir, showing lower mortality with treatment.

risk of death, 39.5% lower, RR 0.61, p = 0.03, treatment 20 of 203 (9.9%), control 63 of 387 (16.3%), NNT 16.

risk of mechanical ventilation, 4.7% lower, RR 0.95, p = 1.00, treatment 7 of 203 (3.4%), control 14 of 387 (3.6%), NNT 591.

hospitalization time, 0.9% higher, relative time 1.01, p = 0.96, treatment mean 11.6 (±7.9) n=203, control mean 11.5 (±9.3) n=387.

Flisiak et al., 6 Jul 2022, retrospective, Poland, peer-reviewed, 13 authors, study period 1 January, 2022 - 30 April, 2022.

Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients

Yip et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac687 (preprint 5/24/2022)

Propensity score weighted retrospective of 93,883 outpatients in Hong Kong, 5,808 treated with molnupiravir and 4,921 treated with paxlovid, showing higher hospitalization and higher combined mortality/mechanical ventilation/ICU admission with molnupiravir, without statistical significance; and lower hospitalization and combined mortality/mechanical ventilation/ICU admission with paxlovid, statistically significant only for hospitalization.

combined death/ventilation/ICU, 12.0% higher, HR 1.12, p = 0.66, treatment 53 of 5,808 (0.9%), control 151 of 83,154 (0.2%), propensity score weighting, Cox proportional hazards, day 30.

risk of hospitalization, 17.0% higher, HR 1.17, p = 0.06, treatment 437 of 5,808 (7.5%), control 1,322 of 83,154 (1.6%), propensity score weighting, Cox proportional hazards, day 30.

Yip et al., 24 May 2022, retrospective, placebo-controlled, China, peer-reviewed, 11 authors, study period 16 February, 2022 - 31 March, 2022.

Real-world effectiveness of early molnupiravir or nirmatrelvir–ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study

Wong et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(22)00507-2 (preprint 5/20/2022)

PSM retrospective 40,776 patients in Hong Kong, showing lower mortality and lower combined mortality, ventilation, ICU, and oxygen therapy with molnupiravir treatment.

risk of death, 52.0% lower, HR 0.48, p < 0.001, treatment 1,856, control 1,856, propensity score matching.

risk of mechanical ventilation, 58.0% lower, HR 0.42, p = 0.06, treatment 1,856, control 1,856, propensity score matching.

combined death/ventilation/ICU/oxygen, 40.0% lower, HR 0.60, p < 0.001, treatment 1,856, control 1,856, propensity score matching.

hospitalization time, 5.9% lower, relative time 0.94, p = 0.03, treatment 1,856, control 1,856, propensity score matching.

Ct<30, 27.5% lower, HR 0.72, p < 0.001, treatment 1,856, control 1,856, inverted to make RR<1 favor treatment, propensity score matching.

Wong et al., 20 May 2022, retrospective, China, peer-reviewed, 6 authors, study period 26 February, 2022 - 26 April, 2022.

Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model

Rosenke et al., JCI Insight, doi:10.1172/jci.insight.160108

Syrian hamster study showing efficacy of molnupiravir for multiple variants including omicron.

Rosenke et al., 17 May 2022, United Kingdom, peer-reviewed, 11 authors.

Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity

Hadj Hassine et al., Viruses, doi:10.3390/v14040841 (Review)

Review of lethal mutagenesis for RNA viruses, as used by molnupiravir, favipiravir, and ribavirin. Authors note the potential for permanently modifying the genomes of patients while causing teratogenicity or embryotoxicity, and the potential of creating novel virus variants with increased pathogenicity and transmissibility.

Authors recommend a registry of patients for long-term monitoring of potential adverse effects, including genetic, carcinogenic, teratogenic, and embryotoxic damage.

Hadj Hassine et al., 18 Apr 2022, peer-reviewed, 3 authors.

PANORAMIC recruitment analysis

Lee, T. (News)

Analysis of the PANORAMIC trial recuitment suggesting that if the trial shows efficacy, the NNT will be >200.

Lee et al., 8 Apr 2022, preprint, 1 author.

Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial

Thorlund et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.21-1339 (Review)

Discussion of concerns with the MOVe-OUT trial, including the reversal of the treatment effect post-interim analysis.

Thorlund et al., 11 Mar 2022, peer-reviewed, 5 authors.

Efficacy and Safety of Molnupiravir for the Treatment of Non-Hospitalized Adults With Mild COVID-19: A Randomized, Open-Label, Parallel-Group Phase 3 Trial

Tippabhotla et al., SSRN Electronic Journal, doi:10.2139/ssrn.4042673

RCT 1,220 patients in India, showing lower risk of hospitalization and improved recovery with treatment. CTRI/2021/07/034588.

risk of hospitalization, 46.2% lower, RR 0.54, p = 0.26, treatment 7 of 610 (1.1%), control 13 of 610 (2.1%), NNT 102, day 28.

risk of no improvement, 46.4% lower, RR 0.54, p < 0.001, treatment 67 of 610 (11.0%), control 125 of 610 (20.5%), NNT 11, day 14.

risk of no improvement, 52.3% lower, RR 0.48, p < 0.001, treatment 199 of 610 (32.6%), control 417 of 610 (68.4%), NNT 2.8, day 10.

risk of no improvement, 24.8% lower, RR 0.75, p < 0.001, treatment 433 of 610 (71.0%), control 576 of 610 (94.4%), NNT 4.3, day 5.

risk of no viral clearance, 59.2% lower, RR 0.41, p < 0.001, treatment 42 of 610 (6.9%), control 103 of 610 (16.9%), NNT 10.0, day 14.

risk of no viral clearance, 81.0% lower, RR 0.19, p < 0.001, treatment 62 of 610 (10.2%), control 327 of 610 (53.6%), NNT 2.3, day 10.

risk of no viral clearance, 77.6% lower, RR 0.22, p < 0.001, treatment 113 of 610 (18.5%), control 505 of 610 (82.8%), NNT 1.6, day 5.

Tippabhotla et al., 24 Feb 2022, Randomized Controlled Trial, India, peer-reviewed, 5 authors, study period 1 July, 2021 - 24 August, 2021, average treatment delay 3.0 days.

Lethal mutagenesis as an antiviral strategy

Swanstrom et al., Science, doi:10.1126/science.abn0048 (Review)

Review of the unknown long-term cancer, reproductive, and escape variant creation risks of molnupiravir. For more discussion see [twitter.com, twitter.com (B), twitter.com (C)].

1. twitter.com, https://twitter.com/michaelzlin/status/1489414600067993605.

2. twitter.com (B), https://twitter.com/michaelzlin/status/1478074270328639488.

3. twitter.com (C), https://twitter.com/michaelzlin/status/1485794533975597064.

Swanstrom et al., 3 Feb 2022, peer-reviewed, 2 authors.

Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir

Waters et al., Environmental and Molecular Mutagenesis, doi:10.1002/em.22471 (Review)

Review of antiviral nucleoside analog drugs that induce lethal mutagenesis, including molnupiravir and favipiravir, and the potential mutagenic risks to human DNA and human mitochondrial DNA. Author recommends monitoring for mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity.

Waters et al., 28 Jan 2022, USA, peer-reviewed, 5 authors.

Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19

Arribas et al., NEJM Evidence, doi:10.1056/EVIDoa2100044

RCT 304 hospitalized patients, 218 treated with molnupiravir, showing no significant differences. MOVe-IN MK-4482-001. NCT04575584.

risk of death, 281.9% higher, RR 3.82, p = 0.31, treatment 11 of 216 (5.1%), control 1 of 75 (1.3%), combined, excluding imputed deaths.

risk of death, 216.9% higher, RR 3.17, p = 0.36, treatment 3 of 71 (4.2%), control 1 of 75 (1.3%), 800mg, excluding imputed death.

risk of death, 316.7% higher, RR 4.17, p = 0.20, treatment 4 of 72 (5.6%), control 1 of 75 (1.3%), 400mg, excluding imputed death.

risk of death, 311.0% higher, RR 4.11, p = 0.21, treatment 4 of 73 (5.5%), control 1 of 75 (1.3%), 200mg.

risk of no recovery, 1.0% lower, RR 0.99, p = 0.96, treatment 72, control 75, inverted to make RR<1 favor treatment, 800mg.

risk of no recovery, 11.5% lower, RR 0.88, p = 0.53, treatment 73, control 75, inverted to make RR<1 favor treatment, 400mg.

risk of no recovery, 1.0% higher, RR 1.01, p = 0.96, treatment 73, control 75, inverted to make RR<1 favor treatment, 200mg.

recovery time, no change, relative time 1.00, treatment 72, control 75, 800mg.

recovery time, no change, relative time 1.00, treatment 73, control 75, 400mg.

recovery time, no change, relative time 1.00, treatment 73, control 75, 200mg.

risk of no viral clearance, 11.8% lower, RR 0.88, p = 0.57, treatment 26 of 52 (50.0%), control 34 of 60 (56.7%), NNT 15, 800mg, Table S16, day 15 mid-recovery.

risk of no viral clearance, 2.4% higher, RR 1.02, p = 1.00, treatment 29 of 50 (58.0%), control 34 of 60 (56.7%), 400mg, Table S16, day 15 mid-recovery.

risk of no viral clearance, 20.6% lower, RR 0.79, p = 0.27, treatment 27 of 60 (45.0%), control 34 of 60 (56.7%), NNT 8.6, 200mg, Table S16, day 15 mid-recovery.

risk of no viral clearance, 8.3% lower, RR 0.92, p = 1.00, treatment 9 of 53 (17.0%), control 10 of 54 (18.5%), NNT 65, 800mg, Table S16, day 29.

risk of no viral clearance, 48.2% higher, RR 1.48, p = 0.35, treatment 14 of 51 (27.5%), control 10 of 54 (18.5%), 400mg, Table S16, day 29.

risk of no viral clearance, 21.5% lower, RR 0.79, p = 0.61, treatment 8 of 55 (14.5%), control 10 of 54 (18.5%), NNT 25, 200mg, Table S16, day 29.

Arribas et al., 16 Dec 2021, Double Blind Randomized Controlled Trial, multiple countries, peer-reviewed, 21 authors, average treatment delay 7.1 days, trial NCT04575584 (history).

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

Jayk Bernal et al., New England Journal of Medicine, doi:10.1056/NEJMoa2116044

MOVe-OUT RCT, showing significantly lower risk of hospitalization or death. In subgroup analysis efficacy was much lower with the delta variant. NCT04575597.

Discussion of concerns with this trial can be found at [defyccc.com, trialsitenews.com]. See also: [twitter.com, twitter.com (B)].

1. defyccc.com, https://defyccc.com/wp-content/upl..vir-Mutagenic-Carcinogenic-TSN.pdf.

2. trialsitenews.com, https://trialsitenews.com/molnupir..carcinogenic-authorized-in-the-uk/.

3. twitter.com, https://twitter.com/Covid19Crusher/status/1464249681446420485.

4. twitter.com (B), https://twitter.com/Covid19Crusher/status/1464269071818661893.

risk of death, 89.0% lower, RR 0.11, p = 0.01, treatment 1 of 709 (0.1%), control 9 of 699 (1.3%), NNT 87.

risk of death/hospitalization, 30.4% lower, RR 0.70, p = 0.05, treatment 48 of 709 (6.8%), control 68 of 699 (9.7%), NNT 34, primary outcome.

risk of death/hosp. (gamma variant), 94.1% lower, RR 0.06, p = 0.004, treatment 0 of 37 (0.0%), control 9 of 47 (19.1%), NNT 5.2, relative risk is not 0 because of continuity correction due to zero events.

risk of death/hosp. (mu variant), 49.5% lower, RR 0.50, p = 0.15, treatment 6 of 75 (8.0%), control 13 of 82 (15.9%), NNT 13.

risk of death/hosp. (delta variant), 23.7% lower, RR 0.76, p = 0.41, treatment 18 of 237 (7.6%), control 22 of 221 (10.0%), NNT 42.

risk of death/hosp. (other variants), 42.2% lower, RR 0.58, p = 0.36, treatment 5 of 47 (10.6%), control 7 of 38 (18.4%), NNT 13.

Jayk Bernal et al., 16 Dec 2021, Randomized Controlled Trial, multiple countries, peer-reviewed, 22 authors, average treatment delay 4.0 days, trial NCT04575597 (history).

Treating a Pandemic Respiratory Disease with a Mutagen is a Doomsday Scenario

Anonymous, Authorea, doi:10.22541/au.163854323.34557301/v1 (Review) (Preprint)

Review of molnupiravir's mutagenic mechanism of action, and analysis of the increased probability of creating dangerous variants.

Anonymous et al., 3 Dec 2021, preprint, 1 author.

Molnupiravir: mutagenic, carcinogenic, authorized in the UK

Goldstein, L., TrialSite News (Review) (News)

Discussion of concerns with molnupiravir and the MOVe-OUT trial. Author notes that results showing bone marrow toxicity in dogs were mentioned in this preprint [medrxiv.org], but removed from the journal version [journals.asm.org]. Some additional details were provided by the UK regulator:

“Reversible, dose-related bone marrow toxicity affecting all haematopoietic cell lines was observed in dogs at ≥17 mg/kg/day (0.4 times the human NHC exposure at the recommended human dose (RHD)).” [gov.uk]

For those without TrialSite News access, this article can also be found at [defyccc.com].

1. defyccc.com, https://defyccc.com/wp-content/upl..vir-Mutagenic-Carcinogenic-TSN.pdf.

2. gov.uk, https://www.gov.uk/government/publ..oduct-characteristics-for-lagevrio.

3. journals.asm.org, https://journals.asm.org/doi/full/10.1128/AAC.02428-20.

4. medrxiv.org, https://www.medrxiv.org/content/10.1101/2020.12.10.20235747v1.

Goldstein et al., 6 Nov 2021, preprint, 1 author.

Two Indian drugmakers to end trials of generic Merck pill for moderate COVID-19

Reuters (News)

Trial CTRI/2021/08/035424 for moderate condition patients has been reported as terminated for futility. Results are not available yet [trialsearch.who.int].

1. trialsearch.who.int, https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2021/08/035424.

Reuters et al., 9 Oct 2021, Randomized Controlled Trial, India, preprint, 1 author.

Two Indian drugmakers to end trials of generic Merck pill for moderate COVID-19

Reuters (News)

Trial CTRI/2021/05/033864 for moderate condition patients has been reported as terminated for futility. Results are not available yet [trialsearch.who.int].

1. trialsearch.who.int, https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2021/08/035424.

Reuters et al., 9 Oct 2021, Randomized Controlled Trial, India, preprint, 1 author.

Molnupiravir: coding for catastrophe

Malone et al., Nature Structural & Molecular Biology, doi:10.1038/s41594-021-00657-8 (Review)

Review of recent studies on molnupiravir's mechanism of lethal mutagenesis. Authors note that potential off-target effects require further investigation, because molnupiravir may be mutagenic to host DNA during host DNA replication.

Malone et al., 13 Sep 2021, peer-reviewed, 2 authors.

Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study

Khoo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkab318

Dose and safety study of molnupiravir with 18 participants, finding no serious adverse events in short-term followup. There was no significant difference in clinical outcomes. NCT04746183.

risk of no recovery, 33.3% higher, RR 1.33, p = 0.63, treatment 8 of 12 (66.7%), control 3 of 6 (50.0%), all dosages, symptomatic at day 15.

risk of no recovery, 100% higher, RR 2.00, p = 0.61, treatment 4 of 12 (33.3%), control 1 of 6 (16.7%), all dosages, symptomatic at day 29.

risk of no recovery, 100% higher, RR 2.00, p = 0.20, treatment 4 of 4 (100.0%), control 3 of 6 (50.0%), 800mg, symptomatic at day 15.

risk of no recovery, no change, RR 1.00, p = 1.00, treatment 2 of 4 (50.0%), control 3 of 6 (50.0%), 600mg, symptomatic at day 15.

risk of no recovery, no change, RR 1.00, p = 1.00, treatment 2 of 4 (50.0%), control 3 of 6 (50.0%), 300mg, symptomatic at day 15.

risk of no recovery, 50.0% higher, RR 1.50, p = 1.00, treatment 1 of 4 (25.0%), control 1 of 6 (16.7%), 800mg, symptomatic at day 29.

risk of no recovery, 200.0% higher, RR 3.00, p = 0.50, treatment 2 of 4 (50.0%), control 1 of 6 (16.7%), 600mg, symptomatic at day 29.

risk of no recovery, 50.0% higher, RR 1.50, p = 1.00, treatment 1 of 4 (25.0%), control 1 of 6 (16.7%), 300mg, symptomatic at day 29.

Khoo et al., 27 Aug 2021, Randomized Controlled Trial, United Kingdom, peer-reviewed, 38 authors, average treatment delay 4.0 days, trial NCT04746183 (history).

Optimus announces Interim Clinical Results from Phase III Clinical Trials of Molnupiravir conducted in India

Optimus Press Release (News)

Interim report on CTRI/2021/06/033992, showing faster viral clearance. Event counts are approximate, the press release only provides percentages.

risk of no viral clearance, 58.0% lower, RR 0.42, p < 0.001, treatment 38 of 175 (21.7%), control 93 of 180 (51.7%), NNT 3.3, day 5.

Optimus et al., 21 Jul 2021, Randomized Controlled Trial, India, preprint, 1 author.

Hetero Announces Interim Clinical Results from Phase III Clinical Trials of Molnupiravir conducted in India

Hetero Press Release

Interim results for CTRI/2021/05/033739, showing lower mortality and faster recovery.

risk of hospitalization, 69.6% lower, RR 0.30, p = 0.003, treatment 7 of 371 (1.9%), control 23 of 370 (6.2%), NNT 23.

recovery time, 33.3% lower, relative time 0.67, p < 0.001, treatment 371, control 370.

Hetero et al., 9 Jul 2021, Randomized Controlled Trial, India, peer-reviewed, 1 author.

Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model

Abdelnabi et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiab361

Hamster study showing molnupiravir effective against the original, B.1.1.7, and B.1.351 variants.

Abdelnabi et al., 9 Jul 2021, peer-reviewed, 6 authors.

Molnupiravir, an Oral Antiviral Treatment for COVID-19

Fischer et al., medRxiv, doi:10.1101/2021.06.17.21258639 (Preprint)

RCT 202 outpatients in the USA showing significantly faster viral clearance, but no significant differences in symptom duration or severity. NCT04405570.

risk of death, 76.5% lower, RR 0.23, p = 0.31, treatment 0 of 140 (0.0%), control 1 of 62 (1.6%), NNT 62, relative risk is not 0 because of continuity correction due to zero events, all.

risk of death, 65.4% lower, RR 0.35, p = 1.00, treatment 0 of 55 (0.0%), control 1 of 62 (1.6%), NNT 62, relative risk is not 0 because of continuity correction due to zero events, 800mg.

risk of death, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 62 (0.0%), control 1 of 62 (1.6%), NNT 62, relative risk is not 0 because of continuity correction due to zero events, 400mg.

risk of death, 57.8% lower, RR 0.42, p = 1.00, treatment 0 of 23 (0.0%), control 1 of 62 (1.6%), NNT 62, relative risk is not 0 because of continuity correction due to zero events, 200mg.

risk of hospitalization, 32.9% higher, RR 1.33, p = 1.00, treatment 3 of 140 (2.1%), control 1 of 62 (1.6%), all.

risk of hospitalization, 12.7% higher, RR 1.13, p = 1.00, treatment 1 of 55 (1.8%), control 1 of 62 (1.6%), 800mg.

risk of hospitalization, 100% higher, RR 2.00, p = 1.00, treatment 2 of 62 (3.2%), control 1 of 62 (1.6%), 400mg.

risk of hospitalization, 57.8% lower, RR 0.42, p = 1.00, treatment 0 of 23 (0.0%), control 1 of 62 (1.6%), NNT 62, relative risk is not 0 because of continuity correction due to zero events, 200mg.

risk of no viral clearance, 49.2% lower, RR 0.51, p = 0.12, treatment 10 of 118 (8.5%), control 9 of 54 (16.7%), NNT 12, infectious, day 3, all.

risk of no viral clearance, 88.7% lower, RR 0.11, p = 0.02, treatment 1 of 53 (1.9%), control 9 of 54 (16.7%), NNT 6.8, infectious, day 3, 800mg.

risk of no viral clearance, 30.2% lower, RR 0.70, p = 0.57, treatment 5 of 43 (11.6%), control 9 of 54 (16.7%), NNT 20, infectious, day 3, 400mg.

risk of no viral clearance, 9.1% higher, RR 1.09, p = 1.00, treatment 4 of 22 (18.2%), control 9 of 54 (16.7%), infectious, day 3, 200mg.

risk of no viral clearance, 92.3% lower, RR 0.08, p = 0.004, treatment 1 of 117 (0.9%), control 6 of 54 (11.1%), NNT 9.8, infectious, day 5, all.

risk of no viral clearance, 92.2% lower, RR 0.08, p = 0.03, treatment 0 of 53 (0.0%), control 6 of 54 (11.1%), NNT 9.0, relative risk is not 0 because of continuity correction due to zero events, infectious, day 5, 800mg.

risk of no viral clearance, 91.4% lower, RR 0.09, p = 0.03, treatment 0 of 42 (0.0%), control 6 of 54 (11.1%), NNT 9.0, relative risk is not 0 because of continuity correction due to zero events, infectious, day 5, 400mg.

risk of no viral clearance, 59.1% lower, RR 0.41, p = 0.67, treatment 1 of 22 (4.5%), control 6 of 54 (11.1%), NNT 15, infectious, day 5, 200mg.

risk of no viral clearance, 29.5% lower, RR 0.70, p = 0.30, treatment 19 of 137 (13.9%), control 12 of 61 (19.7%), NNT 17, all.

risk of no viral clearance, 61.6% lower, RR 0.38, p = 0.10, treatment 4 of 53 (7.5%), control 12 of 61 (19.7%), NNT 8.2, 800mg.

risk of no viral clearance, 8.3% higher, RR 1.08, p = 1.00, treatment 13 of 61 (21.3%), control 12 of 61 (19.7%), 400mg.

risk of no viral clearance, 55.8% lower, RR 0.44, p = 0.33, treatment 2 of 23 (8.7%), control 12 of 61 (19.7%), NNT 9.1, 200mg.

Fischer et al., 18 Jun 2021, Randomized Controlled Trial, USA, preprint, 18 authors, average treatment delay 4.6 days, trial NCT04405570 (history).

β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells

Zhou et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiab247 (In Vitro)

In Vitro study showing that NHC (initial metabolite of molnupiravir) has high antiviral activity against SARS-CoV-2, but also shows host mutational activity in an animal cell culture assay. Authors note the concern that mutations in host DNA could contribute to the development of cancer, or cause birth defects either in a developing fetus or through incorporation into sperm precursor cells. Response from Merck: [academic.oup.com].

1. academic.oup.com, https://academic.oup.com/jid/advan..doi/10.1093/infdis/jiab362/6319402.

Zhou et al., 7 May 2021, peer-reviewed, 10 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Merck and Ridgeback Biotherapeutics Provide Update on Progress of Clinical Development Program for Molnupiravir, an Investigational Oral Therapeutic for the Treatment of Mild-to-Moderate COVID-19

Merck, News Release (Preprint)

News release reporting that the trial of molnupiravir with hospitalized patients (NCT04575584) has been discontinued because data indicates it is unlikely to demonstrate a clinical benefit in hospitalized patients. Results are not available yet. Interim results for the trial with outpatients show positive dose-dependent results for viral clearance.

Merck et al., 15 Apr 2021, preprint, 1 author, trial NCT04575584 (history).