{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:43:46Z","timestamp":1792118626240,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Leg ulcers are a debilitating complication of sickle cell disease (SCD, including sickle cell anaemia and other sickle cell disorders) and have no proven treatments. Resolution of Sickle Cell Leg Ulcers with Voxelotor (RESOLVE) was a Phase 3, randomised, double\u2010blind, placebo\u2010controlled trial evaluating voxelotor for leg ulcer resolution in participants aged \u226512\u2009years with SCD (homozygous haemoglobin S [HbSS]\/haemoglobin S \u03b2\n                    <jats:sup>0<\/jats:sup>\n                    \u2010thalassaemia [HbS\u03b2\n                    <jats:sup>0<\/jats:sup>\n                    ]) and \u22651 active cutaneous lower\u2010extremity ulcer. Participants from Kenya, Nigeria and Brazil were randomised 1:1 to voxelotor 1500\u2009mg (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200945) or placebo (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200943) for 12\u2009weeks. The primary end\u2010point, complete resolution of all target ulcer(s) at Week 12, was not met (achieved resolution: voxelotor 6.7% [3\/45], placebo 7.0% [3\/43]; two\u2010sided\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.99). After Week 12, both groups received open\u2010label voxelotor. During this period, dosing was paused in May 2024, when preliminary data from four voxelotor trials, including RESOLVE, showed safety signals and potential risks that required further analysis. The trial was discontinued in September 2024 when voxelotor was withdrawn from all markets globally. In final safety analyses for RESOLVE, the most common SCD\u2010related treatment\u2010emergent adverse event (TEAE) was sickle cell anaemia with crisis (randomised period: voxelotor 44.4%, placebo 25.6%; open\u2010label period: continuing\u2010voxelotor 60.5%, delayed\u2010voxelotor 53.5%). Eleven participants had fatal events, nine when receiving voxelotor and two after voxelotor was paused (one after ~1\u2009week; one after ~4\u2009months); no deaths were considered treatment\u2010related. In conclusion, leg ulcer resolution was similar between groups, and the voxelotor arm had a higher rate of TEAEs.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70856","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:46:13Z","timestamp":1792115173000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase 3, randomised, placebo\u2010controlled trial of voxelotor for the resolution of leg ulcers in sickle cell disease:\n                    <scp>RESOLVE<\/scp>"],"prefix":"10.1111","author":[{"given":"Bernhards","family":"Ogutu","sequence":"first","affiliation":[{"name":"Centre for Clinical Research Kenya Medical Research Institute (KEMRI)  Nairobi Kenya"},{"name":"CREATES, Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Oyieko","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research Kenya Medical Research Institute (KEMRI)  Nairobi Kenya"},{"name":"Kenya Medical Research Institute\/Walter Reed Army Institute of Research\u2013Africa\/Kenya (KEMRI\u2010WRAIR\/A\u2010K)  Kisumu Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9993-4548","authenticated-orcid":false,"given":"Halima","family":"Bello\u2010Manga","sequence":"additional","affiliation":[{"name":"Barau Dikko Teaching Hospital\/Kaduna State University  Kaduna Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeseye","family":"Akinsete","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Lagos  Idi\u2010Araba, Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie","family":"Githanga","sequence":"additional","affiliation":[{"name":"University of Nairobi  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Valber Lima","family":"Meneses","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of Bahia Universidade Federal da Bahia  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Pfizer Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Davis","sequence":"additional","affiliation":[{"name":"Pfizer Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8751-3834","authenticated-orcid":false,"given":"Jeremy","family":"Rupon","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Ray","family":"Yu","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Pinto","sequence":"additional","affiliation":[{"name":"Pfizer  Porto Salvo Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tudone","sequence":"additional","affiliation":[{"name":"Pfizer  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Musa","family":"Idris","sequence":"additional","affiliation":[{"name":"Aminu Kano Teaching Hospital\/Bayero University Kano  Kano Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Meremikwu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Cochrane Nigeria Institute of Tropical Diseases Research and Prevention, University of Calabar Teaching Hospital  Calabar Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aderson","family":"da Silva Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Hematology Funda\u00e7\u00e3o de Hematologia e Hemoterapia de Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3269-3780","authenticated-orcid":false,"given":"Rodolfo D.","family":"Can\u00e7ado","sequence":"additional","affiliation":[{"name":"Hospital Samaritano  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Fonseca","sequence":"additional","affiliation":[{"name":"University of S\u00e3o Paulo (EEFE\u2010USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Santos Resende","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Clinical Hospital of the Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4801-3156","authenticated-orcid":false,"given":"Obiageli Eunice","family":"Nnodu","sequence":"additional","affiliation":[{"name":"Department of Haematology and Blood Transfusion University of Abuja College of Health Sciences  Abuja Nigeria"},{"name":"Department of Haematology and Blood Transfusion University of Abuja Teaching Hospital  Gwagwalada Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the RESOLVE Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle cell disease","volume":"4","author":"Kato GJ","year":"2018","journal-title":"Nat Rev Dis 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