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Over the past decade, there has been an increased understanding of the pathophysiology of <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>. While multiple drugs have been tested, only one drug, hydroxycarbamide, is approved by the relevant regulatory agencies specifically for this disease. Due to the combination of an improved understanding of disease pathophysiology, governmental support and the success of several recently approved drugs for other\u00a0orphan diseases, there is an increased interest in the development of targeted drugs for <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>. Novel drugs that are currently being evaluated include haemoglobin F inducers, anti\u2010sickling agents, anti\u2010oxidants, anti\u2010adhesive agents, anti\u2010inflammatory agents, anticoagulants and anti\u2010platelet agents. In addition to the evaluation of acute pain crisis as a study endpoint, clinical trials employing other <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>\u2010related complications, exercise capacity, as well as patient reported outcomes are warranted and necessary in order to advance the development of these novel therapeutic agents. Finally, despite the availability of multiple biomarkers, many of these are of limited clinical value in <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> and require further assessment in prospective studies to validate their prognostic importance before they are acceptable as surrogate endpoints.<\/jats:p>","DOI":"10.1111\/bjh.13548","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T09:37:14Z","timestamp":1435657034000},"page":"768-780","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The trials and hopes for drug development in sickle cell disease"],"prefix":"10.1111","volume":"170","author":[{"given":"Kenneth I.","family":"Ataga","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology University of North Carolina Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Stocker","sequence":"additional","affiliation":[{"name":"Selexys Pharmaceuticals Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050460"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199202273260905"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199807023390102"},{"key":"e_1_2_12_5_1","first-page":"273","article-title":"Iron chelators hydroxyurea and bathophenanthroline disulfonate inhibit DNA synthesis by different pathways","volume":"34","author":"Alca\u00edn F.J.","year":"1994","journal-title":"Biochemistry and Molecular Biology International"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200610-1498OC"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2007.1.91"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06110.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-110098"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08520.x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7525-4-59"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08097.x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3313"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00986.2004"},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1182\/blood.V67.5.1442.1442","article-title":"A collaborative, double\u2010blind, randomized study of cetiedil citrate in sickle cell crisis","volume":"67","author":"Benjamin L.J.","year":"1986","journal-title":"Blood"},{"key":"e_1_2_12_16_1","first-page":"283","article-title":"Effects of cetiedil on monovalent cation permeability in the erythrocyte: an explanation for the efficacy of cetiedil in the treatment of sickle cell anemia","volume":"8","author":"Berkowitz L.R.","year":"1982","journal-title":"Blood Cells"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.9.3082"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2001.113989"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2006.12.008"},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"4701","DOI":"10.1182\/blood.V88.12.4701.bloodjournal88124701","article-title":"A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy","volume":"88","author":"Bridges K.R.","year":"1996","journal-title":"Blood"},{"key":"e_1_2_12_21_1","first-page":"88","article-title":"Multi\u2010center randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children","volume":"124","author":"Brousseau D.C.","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709113371107"},{"key":"e_1_2_12_23_1","first-page":"199","article-title":"Clinical and biological double\u2010blind\u2010study of ticlopidine in preventive treatment of sickle\u2010cell disease crises","volume":"15","author":"Cabannes R.","year":"1984","journal-title":"Agents and Actions. 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