{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T08:38:53Z","timestamp":1784709533834,"version":"3.55.0"},"reference-count":45,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","cysticfibrosisjournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Cystic Fibrosis"],"published-print":{"date-parts":[[2023,9]]},"DOI":"10.1016\/j.jcf.2023.07.006","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T09:13:05Z","timestamp":1690449185000},"page":"949-957","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["Traits, trends and hits of orphan drug designations in cystic fibrosis"],"prefix":"10.1016","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-994X","authenticated-orcid":false,"given":"Enrico","family":"Costa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0228-9421","authenticated-orcid":false,"given":"Silvia","family":"Girotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrika A","family":"van den Ham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cipolli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis K","family":"van der Ent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-9722","authenticated-orcid":false,"given":"Jennifer L.","family":"Taylor-Cousar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7175-1499","authenticated-orcid":false,"given":"Hubert G.M.","family":"Leufkens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jcf.2023.07.006_bib0001","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The future of cystic fibrosis care: a global perspective","volume":"8","author":"Bell","year":"2020","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.jcf.2023.07.006_bib0002","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jcf.2018.05.004","article-title":"CFTR modulator theratyping: current status, gaps and future directions","volume":"18","author":"Clancy","year":"2019","journal-title":"J Cyst Fibros"},{"key":"10.1016\/j.jcf.2023.07.006_bib0003","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1056\/NEJMoa0909825","article-title":"Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation","volume":"363","author":"Accurso","year":"2010","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jcf.2023.07.006_bib0004","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1056\/NEJMoa1409547","article-title":"Lumacaftor\u2013Ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR","volume":"373","author":"Wainwright","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jcf.2023.07.006_bib0005","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1056\/NEJMoa1709846","article-title":"Tezacaftor\u2013Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del","volume":"377","author":"Taylor-Cousar","year":"2017","journal-title":"New Engl J Med"},{"key":"10.1016\/j.jcf.2023.07.006_bib0006","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1056\/NEJMoa1807120","article-title":"VX-445-Tezacaftor-Ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles","volume":"379","author":"Keating","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jcf.2023.07.006_bib0007","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/S0140-6736(19)32597-8","article-title":"Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial","volume":"394","author":"Heijerman","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.jcf.2023.07.006_bib0008","doi-asserted-by":"crossref","DOI":"10.1172\/JCI167957","article-title":"Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist","volume":"133","author":"Nichols","year":"2023","journal-title":"J Clin Investigat"},{"key":"10.1016\/j.jcf.2023.07.006_bib0009","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejrad.2022.110421","article-title":"Chest computed tomography improvement in patients with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: Early report","volume":"154","author":"Bec","year":"2022","journal-title":"Eur J Radiol"},{"key":"10.1016\/j.jcf.2023.07.006_bib0010","doi-asserted-by":"crossref","DOI":"10.1002\/ppul.26485","article-title":"Impact of Elexacaftor-Tezacaftor-Ivacaftor on lung disease in cystic fibrosis","author":"Gushue","year":"2023","journal-title":"Pediatr Pulmonol"},{"key":"10.1016\/j.jcf.2023.07.006_bib0011","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.jcf.2022.03.002","article-title":"Elexacaftor-Tezacaftor- Ivacaftor improves sinonasal outcomes in cystic fibrosis","volume":"21","author":"Stapleton","year":"2022","journal-title":"J Cyst Fibros"},{"key":"10.1016\/j.jcf.2023.07.006_bib0012","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1513\/AnnalsATS.202101-057OC","article-title":"Impact of cystic fibrosis transmembrane conductance regulator therapy on chronic rhinosinusitis and health status: deep learning CT analysis and patient-reported outcomes","volume":"19","author":"Beswick","year":"2022","journal-title":"Ann Am Thorac Soc"},{"key":"10.1016\/j.jcf.2023.07.006_bib0013","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jcf.2022.10.003","article-title":"Elexacaftor\/tezacaftor\/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI","volume":"22","author":"Schwarzenberg","year":"2023","journal-title":"J Cyst Fibros"},{"key":"10.1016\/j.jcf.2023.07.006_bib0014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2019.01662","article-title":"CFTR modulators: the changing face of cystic fibrosis in the era of precision medicine","volume":"10","author":"Lopes-Pacheco","year":"2020","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.jcf.2023.07.006_bib0015","unstructured":"US Food and Drug Administration Orphan Drug Act, Pub L. No. 97-414, 96 Stat. 2049. http:\/\/www.fda.gov\/ForIndustry\/DevelopingProductsforRareDiseasesConditions\/HowtoapplyforOrphanProductDesignation\/ucm364750.htm n.d."},{"key":"10.1016\/j.jcf.2023.07.006_bib0016","unstructured":"Regulation (EC) No 141\/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products (consolidated version. 7\/8\/2009). n.d. http:\/\/eur-lex.europa.eu\/LexUriServ\/LexUriServ.do?uri=OJ:L:2000:018:0001:0005:en:PDF (accessed April 1, 2022)."},{"key":"10.1016\/j.jcf.2023.07.006_bib0017","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s13023-021-01901-6","article-title":"Using four decades of FDA orphan drug designations to describe trends in rare disease drug development: substantial growth seen in development of drugs for rare oncologic, neurologic, and pediatric-onset diseases","volume":"16","author":"Miller","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"10.1016\/j.jcf.2023.07.006_bib0018","doi-asserted-by":"crossref","DOI":"10.1016\/j.drudis.2022.103342","article-title":"Emergent treatments for \u03b2-thalassemia and orphan drug legislations","volume":"27","author":"Costa","year":"2022","journal-title":"Drug Discov Today"},{"key":"10.1016\/j.jcf.2023.07.006_bib0019","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2017-017358","article-title":"Failures to further developing orphan medicinal products after designation granted in Europe: an analysis of marketing authorisation failures and abandoned drugs","volume":"7","author":"Giannuzzi","year":"2017","journal-title":"BMJ Open"},{"key":"10.1016\/j.jcf.2023.07.006_bib0020","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1111\/cts.12980","article-title":"Approval success rates of drug candidates based on target, action, modality, application, and their combinations","volume":"14","author":"Yamaguchi","year":"2021","journal-title":"Clin Transl Sci"},{"key":"10.1016\/j.jcf.2023.07.006_bib0021","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/nbt.2786","article-title":"Clinical development success rates for investigational drugs","volume":"32","author":"Hay","year":"2014","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.jcf.2023.07.006_bib0022","doi-asserted-by":"crossref","DOI":"10.1183\/16000617.0124-2017","article-title":"A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators","volume":"27","author":"Ponzano","year":"2018","journal-title":"Eur Respir Rev"},{"key":"10.1016\/j.jcf.2023.07.006_bib0023","doi-asserted-by":"crossref","first-page":"484","DOI":"10.3390\/antibiotics12030484","article-title":"Current and emerging inhaled antibiotics for chronic pulmonary pseudomonas aeruginosa and staphylococcus aureus infections in cystic fibrosis","volume":"12","author":"Li","year":"2023","journal-title":"Antibiotics"},{"key":"10.1016\/j.jcf.2023.07.006_bib0024","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.drudis.2010.11.006","article-title":"Characteristics of orphan drug applications that fail to achieve marketing approval in the USA","volume":"16","author":"Heemstra","year":"2011","journal-title":"Drug Discov Today"},{"key":"10.1016\/j.jcf.2023.07.006_bib0025","unstructured":"European Commission. Community Register of orphan medicinal products. Available from: https:\/\/ec.europa.eu\/health\/documents\/community-register\/html\/reg_od_act.htm?sort=a (Accessed: 01\/04\/2022) n.d."},{"key":"10.1016\/j.jcf.2023.07.006_bib0026","unstructured":"US Food and Drug Administration. Register of Orphan Drug Designations and Approvals. Available from: https:\/\/www.accessdata.fda.gov\/scripts\/opdlisting\/oopd\/(Accessed: 01\/04\/2022) n.d."},{"key":"10.1016\/j.jcf.2023.07.006_bib0027","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR-Cas9 Gene Editing for Sickle Cell Disease and \u03b2-Thalassemia","volume":"384","author":"Frangoul","year":"2021","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jcf.2023.07.006_bib0028","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jcf.2018.02.006","article-title":"ECFS best practice guidelines: the 2018 revision","volume":"17","author":"Castellani","year":"2018","journal-title":"J Cyst Fibros"},{"key":"10.1016\/j.jcf.2023.07.006_bib0029","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jcf.2020.02.015","article-title":"Cystic Fibrosis Foundation consensus guidelines for the care of individuals with advanced cystic fibrosis lung disease","volume":"19","author":"Kapnadak","year":"2020","journal-title":"J Cyst Fibros"},{"key":"10.1016\/j.jcf.2023.07.006_bib0030","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jcf.2012.10.004","article-title":"Consensus Study Group. Treatment of lung infection in patients with cystic fibrosis: current and future strategies","volume":"11","author":"D\u00f6ring","year":"2012","journal-title":"J Cyst Fibros"},{"key":"10.1016\/j.jcf.2023.07.006_bib0031","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3390\/antibiotics10030338","article-title":"Cystic fibrosis: recent insights into inhaled antibiotic treatment and future perspectives","volume":"10","author":"Taccetti","year":"2021","journal-title":"Antibiotics"},{"key":"10.1016\/j.jcf.2023.07.006_bib0032","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.jcf.2022.01.009","article-title":"Worldwide rates of diagnosis and effective treatment for cystic fibrosis","volume":"21","author":"Guo","year":"2022","journal-title":"J Cyst Fibros"},{"key":"10.1016\/j.jcf.2023.07.006_bib0033","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1056\/NEJM199409083311003","article-title":"Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group","volume":"331","author":"Fuchs","year":"1994","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jcf.2023.07.006_bib0034","unstructured":"Orenti A, Zolin A, Jung A, van Rens J, Fox A, Krasnyk M, et\u00a0al. ECFSPR Annual Report 2020. 2022."},{"key":"10.1016\/j.jcf.2023.07.006_bib0035","unstructured":"Cystic fibrosis foundation patient registry 2021 annual data report 2022. https:\/\/www.cff.org\/sites\/default\/files\/2021-11\/Patient-Registry-Annual-Data-Report.pdf."},{"key":"10.1016\/j.jcf.2023.07.006_bib0036","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S2213-2600(13)70085-7","article-title":"Rare lung disease and orphan drug development","volume":"1","author":"Spagnolo","year":"2013","journal-title":"Lancet Respir Med"},{"issue":"11","key":"10.1016\/j.jcf.2023.07.006_bib0037","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S0169-409X(02)00145-X","article-title":"Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis","volume":"54","author":"Ferrari","year":"2002","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.jcf.2023.07.006_bib0038","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1136\/archdischild-2012-302158","article-title":"Gene therapy in cystic fibrosis","volume":"99","author":"Armstrong","year":"2014","journal-title":"Arch Dis Child"},{"key":"10.1016\/j.jcf.2023.07.006_bib0039","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S0169-409X(02)00145-X","article-title":"Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis","volume":"54","author":"Ferrari","year":"2002","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.jcf.2023.07.006_bib0040","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41467-023-36244-2","article-title":"Future therapies for cystic fibrosis","volume":"14","author":"Allen","year":"2023","journal-title":"Nat Commun"},{"key":"10.1016\/j.jcf.2023.07.006_bib0041","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s13023-022-02350-5","article-title":"The impact of FDA and EMA regulatory decision-making process on the access to CFTR modulators for the treatment of cystic fibrosis","volume":"17","author":"Costa","year":"2022","journal-title":"Orphanet J Rare Dis"},{"key":"10.1016\/j.jcf.2023.07.006_bib0042","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s00228-021-03096-y","article-title":"Removal of the EMA orphan designation upon request of the sponsor: cui prodest?","volume":"77","author":"Montanaro","year":"2021","journal-title":"Eur J Clin Pharmacol"},{"key":"10.1016\/j.jcf.2023.07.006_bib0043","doi-asserted-by":"crossref","DOI":"10.1002\/ppul.25075","article-title":"Drug development for cystic fibrosis","volume":"56","author":"Sanders","year":"2021","journal-title":"Pediatr Pulmonol"},{"key":"10.1016\/j.jcf.2023.07.006_bib0044","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/nrd4468","article-title":"Outcomes of EMA marketing authorization applications: does partnering have an influence?","volume":"13","author":"van den Bogert","year":"2014","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.jcf.2023.07.006_bib0045","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.jcf.2020.05.011","article-title":"Building global development strategies for cf therapeutics during a transitional cftr modulator era","volume":"19","author":"Mayer-Hamblett","year":"2020","journal-title":"J Cyst Fibros"}],"container-title":["Journal of Cystic Fibrosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1569199323008354?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1569199323008354?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T08:18:13Z","timestamp":1756714693000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1569199323008354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["S1569199323008354"],"URL":"https:\/\/doi.org\/10.1016\/j.jcf.2023.07.006","relation":{},"ISSN":["1569-1993"],"issn-type":[{"value":"1569-1993","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Traits, trends and hits of orphan drug designations in cystic fibrosis","name":"articletitle","label":"Article Title"},{"value":"Journal of Cystic Fibrosis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jcf.2023.07.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.","name":"copyright","label":"Copyright"}]}}