{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:13:37Z","timestamp":1784117617743,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Enpatoran is a selective inhibitor of toll\u2010like receptors 7 and 8 (TLR7\/8) that potentially targets pro\u2010inflammatory pathways induced by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102). A phase II study conducted in Brazil, the Philippines, and the USA during the early pandemic phase assessed the safety and efficacy of enpatoran in patients hospitalized with COVID\u201019 pneumonia (NCT04448756). A total of 149 patients, who scored 4 on the World Health Organization's (WHO) 9\u2010point ordinal severity scale, were randomized 1:1:1 and received enpatoran 50\u2009mg (<jats:italic>n<\/jats:italic>\u2009=\u200954) or 100\u2009mg (<jats:italic>n<\/jats:italic>\u2009=\u200946), or placebo (<jats:italic>n<\/jats:italic>\u2009=\u200949) twice daily (b.i.d.) for 14\u2009days plus standard of care. The primary objectives were safety and time to recovery (WHO 9\u2010point scale \u22643). Clinical deterioration (WHO 9\u2010point scale\u2009\u2265\u20095) was a key secondary objective. Treatment\u2010emergent adverse events (TEAEs) were comparable across groups (56.5%\u201363.0%). Treatment\u2010related TEAEs were numerically higher with enpatoran 50\u2009mg (14.8%) than 100\u2009mg (10.9%) or placebo (8.2%). Serious TEAEs were numerically lower with enpatoran (50\u2009mg 9.3%, 100\u2009mg 2.2%) than placebo (18.4%). The primary efficacy objective was not met; median time to recovery was 3.4\u20133.9\u2009days across groups, with placebo\u2010treated patients recovering on average faster than anticipated. Clinical deterioration event\u2010free rates up to Day 7 were 90.6%, 95.6%, and 81.6% with enpatoran 50 mg, 100\u2009mg, and placebo, respectively. Enpatoran was well tolerated by patients acutely ill and hospitalized with COVID\u201019 pneumonia. Positive signals in some secondary end points suggested potential beneficial effects, supporting further evaluation of enpatoran in patients with hyperinflammation due to infection or autoimmunity.<\/jats:p>","DOI":"10.1111\/cts.13658","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T06:24:06Z","timestamp":1698128646000},"page":"2640-2653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Enpatoran in <scp>COVID<\/scp>\u201019 pneumonia: Safety and efficacy results from a phase <scp>II<\/scp> randomized trial"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3916-4021","authenticated-orcid":false,"given":"John E.","family":"McKinnon","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Santiaguel","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine University of the Philippines  Manila Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Murta\u00a0de\u00a0Oliveira","sequence":"additional","affiliation":[{"name":"Ambulat\u00f3rio de Pesquisa Cl\u00ednica, Santa Casa de Miseric\u00f3rdia  Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongzi","family":"Yu","sequence":"additional","affiliation":[{"name":"Global Clinical Development, EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukhy","family":"Khursheed","sequence":"additional","affiliation":[{"name":"Global Patient Safety Merck Serono Ltd. Feltham, UK, an affiliate of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavie","family":"Moreau","sequence":"additional","affiliation":[{"name":"Global Biostatistics, EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Klopp\u2010Schulze","sequence":"additional","affiliation":[{"name":"Translational Medicine, the healthcare business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Shaw","sequence":"additional","affiliation":[{"name":"Translational Medicine, EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Roy","sequence":"additional","affiliation":[{"name":"Global Clinical Development Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy H.","family":"Kao","sequence":"additional","affiliation":[{"name":"Research Unit \u2013 Neuroscience &amp; Immunology EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ANEMONE Study Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.59272"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108234"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17665-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5642"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.558898"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00572.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.2000002"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-00544-4"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161512"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-022-07437-9"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121393"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2012.10.008"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.120.000275"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.842"},{"key":"e_1_2_11_16_1","article-title":"O37\u2009M5049, a novel potent and selective inhibitor of toll\u2010like receptors 7 and 8 (TLR 7\/8)","volume":"7","author":"Sherer B","year":"2020","journal-title":"Lupus Sci Med"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2606"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2022-eular.2860"},{"key":"e_1_2_11_19_1","first-page":"4","article-title":"Ethical principles and guidelines for the protection of human subjects of research","volume":"81","author":"The Belmont Report","year":"2014","journal-title":"J Am Coll Dent"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30483-7"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001282"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007764"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2020.1840621"},{"key":"e_1_2_11_24_1","unstructured":"World Health Organization.Tracking SARS\u2010CoV\u20102 variants.2022. Accessed November 3 2022.http:\/\/who.int\/activities\/tracking\u2010SARS\u2010CoV\u20102\u2010variants"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00331-3"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2031994"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021436"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl4348"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.719115"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.15171\/apb.2015.082"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40290-017-0178-6"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13658","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T12:32:25Z","timestamp":1705840345000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,23]]},"references-count":30,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/cts.13658"],"URL":"https:\/\/doi.org\/10.1111\/cts.13658","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,23]]},"assertion":[{"value":"2023-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}