{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:04:29Z","timestamp":1793898269966,"version":"4.8.0"},"reference-count":27,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"unspecified","delay-in-days":115,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Merck Healthcare KGaA, Darmstadt, Germany","award":["CrossRef Funder ID: 10.13039\/100009945"],"award-info":[{"award-number":["CrossRef Funder ID: 10.13039\/100009945"]}],"id":[{"id":"https:\/\/ror.org\/04vpzfb52","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2025,9,13]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate multiple-ascending doses of enpatoran, a selective toll-like receptor 7\/8 (TLR7\/8) inhibitor with the potential to modulate processes central to lupus pathophysiology, in patients with systemic and cutaneous lupus erythematosus (SLE\/CLE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this randomised, double-blind, placebo-controlled phase Ib trial (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04647708\">NCT04647708<\/jats:ext-link>\n                      ), patients with active SLE\/CLE were randomised 3:1 to enpatoran or placebo across four cohorts. Treatment duration was 12\/24 weeks. All patients had a 2-week safety follow-up. The primary endpoint was safety and tolerability. Secondary endpoints included pharmacokinetics (PK) and clinical response. Change in lupus biomarkers, including interferon gene signature (IFN-GS), was an exploratory endpoint.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>25 patients received placebo (n=6) or enpatoran (n=19); 80% were female, all were white, and the median age was 44 years. By week 12, treatment-emergent adverse events (TEAEs) were reported by 42% of patients across the four enpatoran dose groups and 33% of placebo-treated patients. Enpatoran remained well tolerated to week 24. Most TEAEs (96%) were mild or moderate in severity. There were no serious TEAEs. Enpatoran PK was dose proportional, with peak concentration reached 1\u20132\u2009hours postdose and an apparent half-life of 6\u201310\u2009hours across doses. Greater reductions in Systemic Lupus Erythematosus Disease Activity Index 2000, Physician\u2019s Global Assessment and 28-joint count were observed at week 24 with enpatoran versus placebo. Rapid, dose-dependent and reversible suppression of IFN-GS was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Enpatoran was well tolerated and demonstrated favourable safety and PK profiles in patients with SLE and CLE. Although preliminary, the SLE disease activity and biomarker results support the therapeutic targeting of TLR7\/8 for lupus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04647708\">NCT04647708<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2025-001705","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T07:25:33Z","timestamp":1761290733000},"page":"e001705","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Enpatoran, a first-in-class, selective, orally administered toll-like receptor 7\/8 inhibitor, in systemic and cutaneous lupus erythematosus: results from a randomised, placebo-controlled phase Ib study"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct04647708","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04647708","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05162586","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04647708","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05162586","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Torsten","family":"Witte","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0759-5222","authenticated-orcid":false,"given":"Ruth","family":"Fernandez-Ruiz","sequence":"additional","affiliation":[{"name":"EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezda","family":"Abramova","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Weinelt","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavie","family":"Moreau","sequence":"additional","affiliation":[{"name":"EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Klopp-Schulze","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Shaw","sequence":"additional","affiliation":[{"name":"EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Denis","sequence":"additional","affiliation":[{"name":"EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, University Hospital of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"2026010700560365000_12.2.e001705.1","doi-asserted-by":"publisher","DOI":"10.1177\/2040622310380100"},{"key":"2026010700560365000_12.2.e001705.2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218272"},{"key":"2026010700560365000_12.2.e001705.3","doi-asserted-by":"crossref","DOI":"10.1136\/lupus-2020-000469","article-title":"Living with systemic lupus erythematosus in 2020: a European patient survey","volume":"8","author":"Cornet","year":"2021","journal-title":"Lupus Sci Med"},{"key":"2026010700560365000_12.2.e001705.4","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224762"},{"key":"2026010700560365000_12.2.e001705.5","first-page":"i3","article-title":"Systemic lupus erythematosus diagnosis and management","volume":"56","author":"Thong","year":"2017","journal-title":"Rheumatology (Oxford)"},{"key":"2026010700560365000_12.2.e001705.6","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(22)00304-6"},{"key":"2026010700560365000_12.2.e001705.7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jaut.2014.01.021","article-title":"The classification and diagnosis of cutaneous lupus erythematosus","volume":"48\u201349","author":"Kuhn","year":"2014","journal-title":"J Autoimmun"},{"key":"2026010700560365000_12.2.e001705.8","article-title":"Cutaneous manifestations of systemic lupus erythematosus","volume":"2012","author":"Uva","year":"2012","journal-title":"Autoimmune Dis"},{"key":"2026010700560365000_12.2.e001705.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2010.02.008"},{"key":"2026010700560365000_12.2.e001705.10","first-page":"285","article-title":"Lupus erythematosus. 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