Institute of Medicine (US) Committee on Accelerating Rare Diseases Research and Orphan Product Development, Field MJ, Boat TF (2010) Innovation and the Orphan Drug Act, 1983–2009: Regulatory and Clinical Characteristics of Approved Orphan Drugs. In: Rare Diseases and Orphan Products: Accelerating Research and Development. National Academies Press (US)
Ministry of Health, Labour and Welfare (2025) Overview of the designation system for orphan drugs, orphan medical devices, and orphan regenerative medical products. https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000068484.html. Accessed 8 Apr 2025
Koyama A, Ozaki A, Hori A, Tanimoto T (2024) Tackling Japan’s population crisis by improving the childcare environment. Lancet 404:333–334. https://doi.org/10.1016/S0140-6736(24)01175-9
Bavisetty S, Grody WW, Yazdani S (2013) Emergence of pediatric rare diseases: review of present policies and opportunities for improvement: Review of present policies and opportunities for improvement. Rare Dis 1:e23579. https://doi.org/10.4161/rdis.23579
Article PubMed PubMed Central Google Scholar
Ministry of Health, Labour and Welfare (2024) Overview of national medical expenses in fiscal year 2022. [in Japanese] https://www.mhlw.go.jp/toukei/saikin/hw/k-iryohi/22/dl/kekka.pdf. Accessed 8 Apr 2025
Digital Innovation City Association Digital Innovation City Association (2023) Projected future population of Japan. [in Japanese] https://www.ipss.go.jp/pp-zenkoku/j/zenkoku2023/pp2023_gaiyou.pdf. Accessed 8 Apr 2025
Ueyama E, Kaneko M, Narukawa M (2021) Analysis of pediatric drug approval lag in Japan. Ther Innov Regul Sci 55:336–345. https://doi.org/10.1007/s43441-020-00218-z
Pile HD, Sadiq NM (2025) Isotretinoin. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
Yu AL, Gilman AL, Ozkaynak MF et al (2010) Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 363:1324–1334. https://doi.org/10.1056/NEJMoa0911123
Article CAS PubMed PubMed Central Google Scholar
Yu AL, Gilman AL, Ozkaynak MF et al (2021) Long-term follow-up of a phase III study of ch14.18 (dinutuximab) + cytokine immunotherapy in children with high-risk neuroblastoma: COG study ANBL0032. Clin Cancer Res 27:2179–2189. https://doi.org/10.1158/1078-0432.CCR-20-3909
Article CAS PubMed PubMed Central Google Scholar
Parikh NS, Howard SC, Chantada G et al (2015) SIOP-PODC adapted risk stratification and treatment guidelines: recommendations for neuroblastoma in low- and middle-income settings: SIOP-PODC Adapted Risk Stratification and Treatment. Pediatr Blood Cancer 62:1305–1316. https://doi.org/10.1002/pbc.25501
Article PubMed PubMed Central Google Scholar
Matthay KK, Villablanca JG, Seeger RC et al (1999) Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children’s Cancer Group. N Engl J Med 341:1165–1173. https://doi.org/10.1056/NEJM199910143411601
Article CAS PubMed Google Scholar
Japan Registry of Clinical Trials (jRCT). https://jrct.mhlw.go.jp/en-top. Accessed 23 Jun 2025
Pharmaceuticals and Medical Devices Agency. [in Japanese] https://www.pmda.go.jp/index.html. Accessed 10 Jun 2025
Evaluation Committee on Unapproved or Off-label Drugs with High Medical Needs. [in Japanese] https://www.mhlw.go.jp/stf/shingi/other-iyaku_128701.html. Accessed 22 Jun 2025
Hishiki T, Matsumoto K, Ohira M et al (2018) Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG). Int J Clin Oncol 23:965–973. https://doi.org/10.1007/s10147-018-1281-8
Yoneda A, Shichino H, Hishiki T et al (2024) A nationwide phase II study of delayed local treatment for children with high-risk neuroblastoma: the Japan Children’s Cancer Group Neuroblastoma Committee Trial JN-H-11. Pediatr Blood Cancer 71:e30976. https://doi.org/10.1002/pbc.30976
Article CAS PubMed Google Scholar
Wagner LM, Danks MK (2009) New therapeutic targets for the treatment of high-risk neuroblastoma. J Cell Biochem 107:46–57. https://doi.org/10.1002/jcb.22094
Article CAS PubMed Google Scholar
Hara J, Nitani C, Kawamoto H et al (2021) A phase I/IIa study of antidisialoganglioside antibody dinutuximab in Japanese patients with neuroblastoma. J Pediatr Hematol Oncol 43:e358–e364. https://doi.org/10.1097/mph.0000000000001684
Article CAS PubMed Google Scholar
Enya K, Lim Y, Sengoku S, Kodama K (2023) Increasing orphan drug loss in Japan: trends and R&D strategy for rare diseases. Drug Discov Today 28:103755. https://doi.org/10.1016/j.drudis.2023.103755
Article CAS PubMed Google Scholar
Saitou H, Nakatani D, Myoui A et al (2020) Pediatric drug development in Japan: current issues and perspectives. Clin Pediatr Endocrinol 29:1–7. https://doi.org/10.1297/cpe.29.1
Article PubMed PubMed Central Google Scholar
Pediatric Cancer Neuroblastoma Association Parent’s association. In: Pediatric cancer neuroblastoma. [in Japanese] http://nbj-net.jimdofree.com/. Accessed 24 Feb 2025
Makimoto A, Fujisaki H, Matsumoto K et al (2024) Retinoid therapy for neuroblastoma: historical overview, regulatory challenges, and prospects. Cancers (Basel) 16:544. https://doi.org/10.3390/cancers16030544
Article CAS PubMed Google Scholar
Takeda Pharmaceutical Company (2025) Challenges of rare diseases in Japan. [in Japanese] https://www.takeda.co.jp/patients/rd-support/wp/. Accessed 9 Apr 2025
Notification No. 1023–3 Ministry of Health, Labor and Welfare Pharmaceutical Evaluation Division. [in Japanese] https://www.pmda.go.jp/files/000273721.pdf. Accessed 3 Jul 2025
Ahmed R, Duerr U, Gavenis K et al (2014) Challenges for academic investigator-initiated pediatric trials for rare diseases. Clin Ther 36:184–190. https://doi.org/10.1016/j.clinthera.2014.01.013
Batshaw ML, Groft SC, Krischer JP (2014) Research into rare diseases of childhood. JAMA 311:1729–1730. https://doi.org/10.1001/jama.2013.285873
Article CAS PubMed PubMed Central Google Scholar
Patient-Proposed Healthcare Services. [in Japanese] https://www.mhlw.go.jp/moushideryouyou/professional.html. Accessed 10 Jun 2025
Christiansen H, De Bruin ML, Hallgreen CE (2022) Mandatory requirements for pediatric drug development in the EU and the US for novel drugs-a comparative study. Front Med (Lausanne) 9:1009432. https://doi.org/10.3389/fmed.2022.1009432
Carmack M, Hwang T, Bourgeois FT (2020) Pediatric drug policies supporting safe and effective use of therapeutics in children: a systematic analysis: study examines safe and effective use of therapeutics in children. Health Aff (Millwood) 39:1799–1805. https://doi.org/10.1377/hlthaff.2020.00198
Spadoni C (2019) Pediatric drug development: challenges and opportunities. Curr Ther Res Clin Exp 90:119–122. https://doi.org/10.1016/j.curtheres.2018.12.001
Notification No. 1618 (Drug Approval and Licensing Authority) Pharmaceuticals and Medical Devices Agency. [in Japanese] https://www.pmda.go.jp/files/000274421.pdf. Accessed 14 Apr 2025
Results of the Research Group under the 2024 Health and Labour Sciences Special Research Project “Investigation of Drug Loss Reality and Construction of Solutions”. [In Japanese] https://www.mhlw.go.jp/stf/newpage_56135.html. Accessed 10 Jun 2025
Comments (0)