{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:09:08Z","timestamp":1780549748949,"version":"3.54.1"},"reference-count":45,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Duchenne muscular dystrophy (DMD) is a severe muscle disease with an unmet therapeutic need. Despite ongoing research efforts, only a few medicines have achieved marketing authorisation in the EU to date. We present a regulatory science overview summarising the insights obtained from the evaluation by the Paediatric Committee (PDCO) of the European Medicines Agency (EMA) of paediatric investigation plans (PIPs) for this condition, with the primary objective of providing recommendations for future developments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reviewed the PIPs approved by the PDCO and related regulatory procedures analysimg the available information in our own databases completing it with a search in the EU Clinical Trials Register (EudraCT) and Clinical Trials Information System (CTIS) databases to provide context.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between January 2005 and December 2024, 16 PIPs were agreed. By 2024, 1 PIP has been completed, the remaining ones are ongoing. So far, 3 medicines for the treatment of DMD have received a positive opinion by EMA's Committee for Medicinal Products for Human Use (CHMP). Main characteristics and critical factors contributing to successful developments are outlined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study presents the first in-depth evaluation of PIPs approved within the EU for DMD offering insights into potential strategic approaches for clinical development of investigational medicinal products. It highlights the accumulated experience of regulators and stakeholders, particularly regarding pivotal trials that establish clinical efficacy in key patient subgroups. Furthermore, it underscores the emerging value of innovative methodologies \u2013 such as extrapolation of efficacy and integration of real-world evidence \u2013 while acknowledging persistent challenges related to data quality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/22143602251397736","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T18:03:51Z","timestamp":1763489031000},"page":"405-419","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Paediatric medicines development for Duchenne muscular dystrophy: An EU regulatory perspective"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3520-6880","authenticated-orcid":false,"given":"Sylvie","family":"Benchetrit","sequence":"first","affiliation":[{"name":"Department of Europe and Innovation, Agence nationale de s\u00e9curit\u00e9 du m\u00e9dicament et des produits de sant\u00e9 (ANSM)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Europe and Innovation, Agence nationale de s\u00e9curit\u00e9 du m\u00e9dicament et des produits de sant\u00e9 (ANSM)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-1286","authenticated-orcid":false,"given":"Dimitrios","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"World Duchenne Organization, Veenendaal, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0135-0955","authenticated-orcid":false,"given":"Sabine","family":"Scherer","sequence":"additional","affiliation":[{"name":"Paediatric and Orphan Medicinal Products Unit, Federal Institute for Drugs and Medical Devices (BfArM)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7941-6713","authenticated-orcid":false,"given":"Fernando","family":"de Andres Trelles","sequence":"additional","affiliation":[{"name":"Universidad Complutense"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7521-165X","authenticated-orcid":false,"given":"Violeta","family":"Stoyanova-Beninska","sequence":"additional","affiliation":[{"name":"European Medicines Agency (EMA)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena H","family":"Martinez-Lapiscina","sequence":"additional","affiliation":[{"name":"European Medicines Agency (EMA)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0291-952X","authenticated-orcid":false,"given":"Roberto","family":"De Lisa","sequence":"additional","affiliation":[{"name":"European Medicines Agency (EMA)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00248-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules201018168"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30024-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20586"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21438"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01430-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-417044-5.00030-5"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70271-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-00687-z"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30025-5"},{"key":"e_1_3_3_12_2","unstructured":"European Commission. Regulation (EC) No 1901\/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768\/92 Directive 2001\/20\/EC Directive 2001\/83\/EC and Regulation (EC) No 726\/2004 Official Journal of the European Union."},{"key":"e_1_3_3_13_2","unstructured":"European Medicines Agency. Paediatric investigation plans. 2024 https:\/\/www.ema.europa.eu\/en\/human-regulatory\/research-development\/paediatric-medicines\/paediatric-investigation-plans (accessed 31\/12\/2024)."},{"key":"e_1_3_3_14_2","unstructured":"Committee for Medicinal Products for Human Use (CHMP). Guideline on the clinical investigation of medicinal products for the treatment of Duchenne and Becker muscular dystrophy EMA\/CHMP\/236981\/2011 Corr. 1. https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/research-development\/scientific-guidelines\/multidisciplinary-guidelines\/scientific-guidelines-paediatrics: European Medicines Agency."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.735912"},{"key":"e_1_3_3_16_2","unstructured":"European Medicines Agency. Scientific advice and protocol assistance. 2024 (accessed 31\/12\/2024)."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.698534"},{"key":"e_1_3_3_18_2","unstructured":"EudraCT database. https:\/\/www.clinicaltrialsregister.eu European Medicines Agency 2024."},{"key":"e_1_3_3_19_2","unstructured":"Clinical Trials Information System \u2013 CTIS. https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/research-development\/clinical-trials-human-medicines\/clinical-trials-information-system European Medicines Agency 2024."},{"key":"e_1_3_3_20_2","unstructured":"ClinicalTrial.gov. https:\/\/clinicaltrials.gov\/ National Library of Medicine."},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23902"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0307118"},{"key":"e_1_3_3_23_2","unstructured":"Brown V Merikle E Johnston K et al. A qualitative study to understand the Duchenne muscular dystrophy experience from the parent\/patient perspective."},{"key":"e_1_3_3_24_2","unstructured":"Santhera Pharmaceuticals Holding AG. Santhera\u2019s AGAMREE (Vamorolone) approved in the European Union for the treatment of duchenne muscular dystrophy 2023."},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23807"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0283669"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12213"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3233\/JND-221556"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2009.03316.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2013.04.001"},{"key":"e_1_3_3_31_2","unstructured":"MFM NMD. The Motor Function Measurement (MFM) database. https:\/\/mfm-nmd.org\/the-mfm-database\/?lang=en."},{"key":"e_1_3_3_32_2","unstructured":"Committee for Medicinal Products for Human Use (CHMP). Qualification Opinion for Stride velocity 95th centile as primary endpoint in studies in ambulatory Duchenne Muscular Dystrophy studies EMADOC-1700519818-1127132. European Medicines Agency 2023 https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/qualification-opinion-stride-velocity-95th-centile-primary-endpoint-studies-ambulatory-duchenne-muscular-dystrophy-studies_en.pdf."},{"key":"e_1_3_3_33_2","unstructured":"Muscular Dystrophy Association. Duchenne Muscular Dystrophy (DMD) diagnosis. 2024 https:\/\/www.mda.org\/disease\/duchenne-muscular-dystrophy\/diagnosis (accessed 31\/12\/2024)."},{"key":"e_1_3_3_34_2","unstructured":"Committee for Medicinal Products for Human Use (CHMP). Exondys: EPAR \u2013 Refusal public assessment report EMEA\/H\/C\/004355\/0000. European Medicines Agency 2018 https:\/\/www.ema.europa.eu\/en\/homepage."},{"key":"e_1_3_3_35_2","unstructured":"Committee for Medicinal Products for Human Use (CHMP). Draft Reflection paper on establishing efficacy based on single-arm trials submitted as pivotal evidence in a marketing authorisation \u2013 Considerations on evidence from single-arm trials EMA\/CHMP\/564424\/2021. https:\/\/www.ema.europa.eu\/en\/homepage."},{"key":"e_1_3_3_36_2","unstructured":"Zolgensma: EPAR \u2013 Public assessment report EMA\/200482\/2020. European Medicines Agency 2020 https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/zolgensma#assessment-history."},{"key":"e_1_3_3_37_2","unstructured":"Libmeldy: EPAR \u2013 Public assessment report EMA\/584450\/2020. 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Translarna: EPAR \u2013 Public assessment report EMA\/369266\/2014 https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/translarna."},{"key":"e_1_3_3_45_2","volume-title":"Pediatric Cluster Terms of Reference","author":"European Medicines Agency (EMA) of the European Union (EU) the United States (US) Food and Drug Administration (FDA) Health Canada tPaMDAP","year":"2023","unstructured":"European Medicines Agency (EMA) of the European Union (EU) the United States (US) Food and Drug Administration (FDA) Health Canada tPaMDAP. Pediatric Cluster Terms of Reference. Amsterdam: European Medicines Agency, 2023, www.ema.europa.eu\/system\/files\/documents\/other\/pediatric-cluster-terms-reference-en.pdf."},{"key":"e_1_3_3_46_2","unstructured":"Vassal G Rousseau R Blanc P et al. 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