{"id":10902,"date":"2024-04-08T11:41:20","date_gmt":"2024-04-08T15:41:20","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=10902"},"modified":"2024-04-19T12:13:17","modified_gmt":"2024-04-19T16:13:17","slug":"the-rise-and-fall-of-paxlovid","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/the-rise-and-fall-of-paxlovid\/2024\/04\/08\/","title":{"rendered":"The Rise and Fall of Paxlovid"},"content":{"rendered":"

It’s been quite the ride for our “preferred” outpatient therapy for COVID-19, nirmatrelvir with ritonavir — much better known as Paxlovid, so allow me the license to use the licensed name.<\/p>\n

Let’s recap the astonishing success and now failure of this intervention (some dates approximate):<\/p>\n

    \n
  1. December 2021, the FDA issued an Emergency Use Authorization for Paxlovid<\/strong><\/a>:<\/strong>\u00a0 Action is based on the efficacy shown in the EPIC-HR study of high-risk outpatients with COVID-19. Compared to those receiving placebo, Paxlovid-treated participants had an 89% reduction in risk of hospitalization or death.<\/a><\/strong> Exciting times.<\/li>\n
  2. Early 2022, that annoying rebound thing.<\/strong><\/a> No, it’s never been quite clear whether Paxlovid caused<\/em> rebounds, or just didn’t prevent them, or whether it just happened in those people for whom COVID-19 illness lasted longer than the treatment’s 5 days (a large group!), but regardless — it was a major disincentive to clinicians and providers alike.<\/li>\n
  3. December 2022, the protocol for the EPIC-SR in “standard risk” outpatients was amended to increase the sample size.<\/strong><\/a> Though an interim analysis suggested such patients would benefit from treatment, the change in sample size signaled that such a benefit observed in this analysis might be small — or nonexistent.<\/li>\n
  4. August 2023, the negative results of EPIC-SR were posted on clinicaltrials.gov.<\/a><\/strong> Yes, these results have been in the public domain since last summer.<\/li>\n
  5. Last week, the disappointing EPIC-SR results appeared in the New England Journal of Medicine<\/em>.<\/a><\/strong> This is the primary endpoint (from the Research Summary<\/a>):<\/li>\n<\/ol>\n

    \"\"<\/p>\n

    Oh well.<\/p>\n

    It wasn’t all bad news for treatment: Risks of severe outcomes (hospitalizations, ICU admissions, or deaths) were very low overall — hooray! — and numerically lower in the Paxlovid group; medical visits were significantly lower as well. However, as anyone who has taken Paxlovid can attest, the taste alone could have made study participants aware that they were already on treatment, hence discouraging them from seeking further evaluations.<\/p>\n

    What about rebounds? From these limited data, it appeared there was no difference:<\/p>\n

    By day 14, viral load rebound had occurred in 4.3% of the participants in the nirmatrelvir\u2013ritonavir group and 4.1% of those in the placebo group; symptom rebound occurred in 11.4% and 16.1%, respectively, and symptom and viral load rebound together occurred in 1.2% and 0.5%, respectively.<\/p><\/blockquote>\n

    So where does that leave us right now? There’s no doubt that the EPIC-SR data further confirm that this treatment has many limitations. Here’s a teaching slide I recently made:<\/p>\n

    \"\"<\/p>\n

    (If you’re wondering about the picture of the Fab Four, I can’t reference anything based in Liverpool without citing two of its spectacular exports —\u00a0 the Beatles and the University of Liverpool drug interactions checker<\/a>!)<\/em><\/p>\n

    But before we completely abandon Paxlovid for outpatient use, let’s remember that our options for outpatient treatment of COVID-19 remain highly limited. Furthermore, people at high risk for adverse outcomes still require hospitalization and still die from this infection — as they do from other viral respiratory illnesses. As a result, based on EPIC-HR, these EPIC-SR data, and the observational studies, I’d still recommend treatment for this very high-risk group.<\/p>\n

    For others? Allow me to quote (with his permission) my smart colleague Dr. Athe Tsibris, a virologist who sent me this email after his own unfavorable experience with treatment last fall — the subject line read “Boo Paxlovid”:<\/p>\n

    \n

    Hi Paul,
    \nHaving just gone through Paxlovid rebound with my 1st<\/sup> covid infection (I held out as long as I could!), I’d like to share an entirely unsolicited observation and two rants:
    \n1. The dose and\/or duration is clearly wrong. Started within 48hrs of symptoms and rebounded \u2013 documented with daily antigen tests \u2013 harder than then original infection!
    \n2. The company line of 2% incidence of rebound is laughable
    \nI would not take Paxlovid again. I understand the limitations of human psychology, but for someone very low risk like myself, I don\u2019t know how hard I\u2019d push it on similar patients
    \nAthe<\/p>\n<\/blockquote>\n

    For low-risk people, I totally get it.<\/p>\n

    Meanwhile, the gargantuan PANORAMIC study of Paxlovid in outpatients has closed to enrollment,<\/a> with data collection continuing until September. Will this study provide any further evidence of the benefits or risks of treatment?<\/p>\n

    Regardless of the results, I do hope that the appetite for better treatments for COVID-19 remains, as this virus isn’t going anywhere.<\/p>\n","protected":false},"excerpt":{"rendered":"

    It’s been quite the ride for our “preferred” outpatient therapy for COVID-19, nirmatrelvir with ritonavir — much better known as Paxlovid, so allow me the license to use the licensed name. Let’s recap the astonishing success and now failure of this intervention (some dates approximate): December 2021, the FDA issued an Emergency Use Authorization for […]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,5],"tags":[4601,5831],"class_list":["post-10902","post","type-post","status-publish","format-standard","hentry","category-health-care","category-infectious-diseases","tag-covid-19","tag-paxlovid"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/10902","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=10902"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/10902\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=10902"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=10902"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=10902"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}