{"id":10537,"date":"2022-10-10T17:22:43","date_gmt":"2022-10-10T21:22:43","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=10537"},"modified":"2022-12-23T06:42:35","modified_gmt":"2022-12-23T11:42:35","slug":"molnupiravir-results-in-panoramic-study-its-not-all-bad-news","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/molnupiravir-results-in-panoramic-study-its-not-all-bad-news\/2022\/10\/10\/","title":{"rendered":"Molnupiravir Results in PANORAMIC Study &#8212; It&#8217;s Not All Bad News"},"content":{"rendered":"<p>Last week, the large <a href=\"https:\/\/www.panoramictrial.org\" target=\"_blank\" rel=\"noopener\">PANORAMIC trial of COVID-19 treatment<\/a> in outpatients with mild-moderate disease appeared in <a href=\"https:\/\/papers.ssrn.com\/sol3\/papers.cfm?abstract_id=4237902\" target=\"_blank\" rel=\"noopener\">a pre-print<\/a>. This large (25,783 participants!) randomized, open-label study compared molnupiravir vs. usual care in adults 50 or older, or having comorbidities known to make severe disease more likely.<\/p>\n<p>The results?<\/p>\n<blockquote class=\"twitter-tweet\" data-width=\"500\" data-dnt=\"true\">\n<p lang=\"en\" dir=\"ltr\">Molnupiravir vs standard of care for outpts with Covid19. No difference in the already low rate of hosp\/death, but take a look at this Time to Recovery 2ndary endpoint, a 4-day benefit! Robust across subgroups. Caveat: Open label design. <a href=\"https:\/\/t.co\/t07aqg68s9\">https:\/\/t.co\/t07aqg68s9<\/a> h\/t <a href=\"https:\/\/twitter.com\/ASPphysician?ref_src=twsrc%5Etfw\">@ASPphysician<\/a> <a href=\"https:\/\/t.co\/MExXZLOTp2\">pic.twitter.com\/MExXZLOTp2<\/a><\/p>\n<p>&mdash; Paul Sax (@PaulSaxMD) <a href=\"https:\/\/twitter.com\/PaulSaxMD\/status\/1578086975512334337?ref_src=twsrc%5Etfw\">October 6, 2022<\/a><\/p><\/blockquote>\n<p><script async src=\"https:\/\/platform.twitter.com\/widgets.js\" charset=\"utf-8\"><\/script><\/p>\n<p>Four days faster recovery with treatment! You might think this would be welcome news.<\/p>\n<p>Ah, but think again.\u00a0Because the response from the ID cognoscenti was lukewarm, and that&#8217;s putting it kindly.<\/p>\n<p>Many cited the study&#8217;s open-label design as a major limitation, negating the favorable time-to-recovery result. The placebo effect is certainly in play when a person knows they are receiving active treatment.<\/p>\n<p>Some noted the ongoing concerns with molnupiravir and mutagenicity &#8212; and the theoretical worries about generating variants.<\/p>\n<p>Others criticized the cost of the drug.<\/p>\n<p>But the major theme of the naysayers emphasized the inability of the treatment to demonstrate a benefit in the primary endpoint of interest &#8212; hospitalization or death. Here the result was quite low for both arms, and equal, at 0.8%. Not a bit of difference, and this lack of efficacy is also <a href=\"https:\/\/www.statnews.com\/pharmalot\/2022\/10\/07\/covid19-merck-molnupiravir-fda-mhra-hospitalization\/\" target=\"_blank\" rel=\"noopener\">what the headlines typically featured.<\/a><\/p>\n<p>As a result, when I polled people on whether they would prescribe molnupiravir now that they know the results, it didn&#8217;t surprise me that a majority said no.<\/p>\n<blockquote class=\"twitter-tweet\" data-width=\"500\" data-dnt=\"true\">\n<p lang=\"en\" dir=\"ltr\">Molnupiravir vs usual care in large open-label randomized trial. Pts mostly vaccinated; omicron era: <br \/>&#8211; Primary endpoint:  no difference in hosp\/death (0.8% for both)<br \/>&#8211; 4.2 days faster reported recovery<br \/>&#8211; faster viral clearance<br \/>&#8211; serious AEs 0.4% for both<br \/>Would you prescribe it?<\/p>\n<p>&mdash; Paul Sax (@PaulSaxMD) <a href=\"https:\/\/twitter.com\/PaulSaxMD\/status\/1578707576190951424?ref_src=twsrc%5Etfw\">October 8, 2022<\/a><\/p><\/blockquote>\n<p><script async src=\"https:\/\/platform.twitter.com\/widgets.js\" charset=\"utf-8\"><\/script><\/p>\n<p>With the caveats that this sort of poll is only representative of the people who saw and answered it, and that Twitter can be a really negative place &#8212; like <a href=\"https:\/\/www.nytimes.com\/2022\/10\/06\/opinion\/elon-musk-twitter.html\" target=\"_blank\" rel=\"noopener\">&#8220;staying too late at a bad party full of people who hate you&#8221;<\/a> &#8212; I do think it&#8217;s worth acknowledging these important concerns about both the study and the drug.<\/p>\n<p>But it&#8217;s also worth highlighting the good news coming out of this trial &#8212; and it&#8217;s very good news indeed.<\/p>\n<p>First and foremost, the amazingly low incidence of hospitalization or death underscores how much less severe COVID is now compared to when it first hit the human race. It&#8217;s especially notable since the study population included only those at risk for bad outcomes. When it comes to most infections, it&#8217;s a wonderful thing not to be immunologically naive, and the participants had very <img loading=\"lazy\" decoding=\"async\" class=\"alignright  wp-image-10591\" src=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/dog-gfa9b596fa_1280-1024x682.jpg\" alt=\"\" width=\"437\" height=\"291\" srcset=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/dog-gfa9b596fa_1280-1024x682.jpg 1024w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/dog-gfa9b596fa_1280-300x200.jpg 300w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/dog-gfa9b596fa_1280-768x512.jpg 768w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/dog-gfa9b596fa_1280.jpg 1280w\" sizes=\"auto, (max-width: 437px) 100vw, 437px\" \/>high rates of vaccination and\/or prior infection.<\/p>\n<p>(Parenthetically, the lower disease severity presents a virtually insurmountable challenge to conducting a clinical trial with this &#8220;hospitalization or death&#8221; endpoint &#8212; as <a href=\"https:\/\/twitter.com\/boulware_dr\/status\/1578102169139818496?s=20&amp;t=6OSkP1E2vxm8DnAgeV5mnA\" target=\"_blank\" rel=\"noopener\">noted by Dr. David Boulware<\/a>, the sample size would need to be extraordinarily large.)<\/p>\n<p>Second, let&#8217;s go back to the observed faster time to recovery for a moment. A 4.2-day improvement in time to recovery with no major short-term side effects \u00a0&#8212; or drug interactions &#8212; is nothing to sneeze at, if you&#8217;ll forgive the very apt cliche. As a point of reference, this is quite a bit more than the observed clinical benefit seen with oseltamivir and baloxavir for influenza, which is typically 1-2 days. Note also that there is no mention of clinical or virologic rebounds, though perhaps the researchers did not assess for these endpoints.<\/p>\n<p>So let&#8217;s imagine you are a person with COVID. You&#8217;re miserable &#8212; feverish, sneezing, coughing, out of work. Not hospitalization-level sick, but feeling pretty lousy.<\/p>\n<p>Your doctor tells you they have a 5-day treatment that, in a large study, shortened the time to recovery by 4-5 days compared to people who didn&#8217;t get the treatment.<\/p>\n<p>Plus, there were no major side effects, and the amount of virus dropped faster, too.<\/p>\n<p>Wouldn&#8217;t you at least consider it?<\/p>\n<p>Or, as <a href=\"https:\/\/twitter.com\/sscott86\/status\/1579109796258910209?s=20&amp;t=7hJyXIKLYr7-MJN2qT-AjQ\" target=\"_blank\" rel=\"noopener\">Dr. Sarah Scott writes<\/a>:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-10538\" src=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/Screen-Shot-2022-10-09-at-11.55.53-AM.png\" alt=\"\" width=\"667\" height=\"334\" srcset=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/Screen-Shot-2022-10-09-at-11.55.53-AM.png 1180w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/Screen-Shot-2022-10-09-at-11.55.53-AM-300x150.png 300w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/Screen-Shot-2022-10-09-at-11.55.53-AM-1024x512.png 1024w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/10\/Screen-Shot-2022-10-09-at-11.55.53-AM-768x384.png 768w\" sizes=\"auto, (max-width: 667px) 100vw, 667px\" \/><\/p>\n<p>Well said. While acknowledging that the open-label design makes ascribing this benefit <em>solely<\/em> to the drug is impossible &#8212; people really want to believe that their treatment is making them better &#8212; we can also note that this difference in time to recovery is substantial, even by the standards of other non-placebo controlled trials.<\/p>\n<p>Finally, the PANORAMIC investigators deserve a ton of credit carrying off this very large, pragmatic clinical trial. We all look forward to seeing it go through peer review and revision, information about rebounds (if they happened), as well as the promised follow-up data regarding long COVID. Also, the results of the nirmatrelvir\/r (Paxlovid) arm of the study promise to be particularly interesting, as this is way more widely used than molnupiravir for COVID treatment, at least here in the United States.<\/p>\n<p>Meanwhile, enjoy this video, because I certainly did.<\/p>\n<p><iframe loading=\"lazy\" title=\"Infectious Disease Goes on a Hike\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/FJVR-NCaUac?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Last week, the large PANORAMIC trial of COVID-19 treatment in outpatients with mild-moderate disease appeared in a pre-print. This large (25,783 participants!) randomized, open-label study compared molnupiravir vs. usual care in adults 50 or older, or having comorbidities known to make severe disease more likely. The results? Molnupiravir vs standard of care for outpts with [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,5,8],"tags":[4601,5833,5834],"class_list":["post-10537","post","type-post","status-publish","format-standard","hentry","category-health-care","category-infectious-diseases","category-patient-care","tag-covid-19","tag-molnupiravir","tag-panoramic"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/10537","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/comments?post=10537"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/10537\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=10537"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=10537"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=10537"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}