7

Molnupiravir’s authorisation should be re-evaluated after the Panoramic trial is...

 2 years ago
source link: https://www.bmj.com/content/377/bmj.o973
Go to the source link to view the article. You can view the picture content, updated content and better typesetting reading experience. If the link is broken, please click the button below to view the snapshot at that time.
neoserver,ios ssh client

Letters Molnupiravir’s premature authorisation

Molnupiravir’s authorisation should be re-evaluated after the Panoramic trial is reported

BMJ 2022; 377 doi: https://doi.org/10.1136/bmj.o973 (Published 26 April 2022) Cite this as: BMJ 2022;377:o973

Brophy’s editorial on Merck’s Move-Out trial of molnupiravir raises important concerns about the approval of molnupiravir to treat outpatients with covid-19 in the United Kingdom.1 Molnupiravir has not yet been approved in Europe,2 and orders were recently cancelled in France.3

Molnupiravir reduced the risk of hospital admission or death by 52% versus placebo in the interim analysis but raised risk by 35% among patients subsequently evaluated.4 There was no clear explanation for this substantial disparity in treatment effects between the interim and final phases. Molnupiravir showed no overall benefit over placebo for resolution of covid-19 related signs and symptoms.5

Molnupiravir is now being evaluated in the UK Panoramic trial, coordinated by Oxford University (https://www.panoramictrial.org/). The inclusion criteria and primary efficacy endpoint are similar to the Move-Out trial, with two exceptions. Panoramic includes mainly vaccinated patients, and is being conducted during the Omicron wave, whereas Move-Out included only unvaccinated patients and was conducted in 2021, when previous variants led to more severe disease.

In Panoramic, the original sample size calculation of 10 600 patients assumed a 3% rate of hospital admission or death for standard of care, and 2% for patients taking molnupiravir. By 1 April 2022, Panoramic had enrolled 21 460 patients, over double the original estimate. This suggests that rates of hospital admission or death could be even lower than originally predicted. So the clinical benefits of molnupiravir and associated cost-effectiveness might be lower for vaccinated patients in the current Omicron wave.

As Brophy explains,1 the Move-Out trial was terminated after the interim analysis for ethical reasons, after only 762 patients had been evaluated. By contrast, the Panoramic trial, with the same inclusion criteria and primary endpoint but with a sample size 27 times larger, is still going.

The UK approval of molnupiravir should be re-evaluated after results from the Panoramic trial have been reported.

Footnotes

This article is made freely available for personal use in accordance with BMJ's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

References

  1. ↵
    1. Brophy JM
    . Molnupiravir’s authorisation was premature. BMJ2022;376:o443. doi:10.1136/bmj.o443 pmid:35241455
  2. ↵
    Mancini DP, Smyth J. Merck struggles to win European approval for covid-19 drug. Financial Times 2022 Feb 16. https://www.ft.com/content/2cf0b6cc-b07b-4ff9-a833-42eb1798a576.
  3. ↵
    Spencer M, Parodi E. France cancels orders for Merck’s covid-19 antiviral drug. Reuters 2021 Dec 22. https://www.reuters.com/world/europe/france-cancels-order-mercks-covid-19-antiviral-drug-2021-12-22/.
  4. ↵
    1. Thorlund K,
    2. Sheldrick K,
    3. Meyerowitz-Katz G,
    4. Singh S,
    5. Hill A
    . Making statistical sense of the molnupiravir Move-Out trial. Am J Trop Med Hyg2022;tpmd211339. doi:10.4269/ajtmh.21-1339 pmid:35276667
  5. ↵
    1. Jayk Bernal A,
    2. Gomes da Silva MM,
    3. Musungaie DB,
    4. et al.,
    5. MOVe-OUT Study Group
    . Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med2022;386:509-20. doi:10.1056/NEJMoa2116044 pmid:34914868

report

Recommend

About Joyk


Aggregate valuable and interesting links.
Joyk means Joy of geeK