{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T11:46:02Z","timestamp":1793619962399,"version":"4.5.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"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 Huntington's Disease"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing phase I clinical trial of ALN-HTT02 from Alynlam Pharmaceuticals. We also report on the SAGE-718 (also known as dalzanemdor) program from Sage Therapeutics, with results of the phase II DIMENSION study and the recent termination of the open-label phase III PURVIEW study. Additionally, we discuss recent developments in the regulatory pathway for AMT-130, following discussions between uniQure and the U.S. Food and Drug Administration regarding key aspects of accelerated approval. Finally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease.<\/jats:p>","DOI":"10.1177\/18796397251337000","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T03:18:55Z","timestamp":1745983135000},"page":"191-206","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":35,"title":["Huntington's disease clinical trials update: March 2025"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0679-0117","authenticated-orcid":false,"given":"Mena","family":"Farag","sequence":"first","affiliation":[{"name":"Huntington's Disease Centre, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J","family":"Wild","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-170262"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-189001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-189003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-190001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-199003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-200002"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-229002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-229006"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-239001"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-240017"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/18796397241293955"},{"key":"e_1_3_2_13_2","unstructured":"Alnylam Pharmaceuticals. A study to evaluate ALN-HTT02 in adult patients with Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT06585449 (accessed 5 February 2025)."},{"key":"e_1_3_2_14_2","unstructured":"Sage Therapeutics. A study to evaluate the effect of SAGE-718 on cognitive function in participants with Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT05107128 (accessed 9 February 2025)."},{"key":"e_1_3_2_15_2","unstructured":"Sage Therapeutics. A study to evaluate the safety and tolerability of SAGE-718 in participants with Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT05655520 (accessed 11 February 2025)."},{"key":"e_1_3_2_16_2","unstructured":"UniQure Biopharma B.V. uniQure announces alignment with FDA on key elements of accelerated approval pathway for AMT-130 in Huntington\u2019s disease https:\/\/uniqure.gcs-web.com\/node\/11906\/pdf (accessed 11 February 2025)."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00120-X"},{"key":"e_1_3_2_18_2","unstructured":"Alnylam Pharmaceuticals. A study to evaluate the safety and tolerability of ALN-APP in patients with EOAD https:\/\/clinicaltrials.gov\/study\/NCT05231785 (accessed 5 February 2025)."},{"key":"e_1_3_2_19_2","unstructured":"Alynlam Pharmaceuticals. Alnylam reports additional positive interim Phase 1 results for ALN-APP in development for Alzheimer\u2019s disease and cerebral amyloid angiopathy https:\/\/investors.alnylam.com\/press-release?id=27761 (accessed 5 February 2025)."},{"key":"e_1_3_2_20_2","article-title":"Single ascending dose results from an ongoing Phase 1 study of mivelsiran (ALN-APP), the first investigational RNA interference therapeutic targeting amyloid precursor protein for Alzheimer\u2019s disease","volume":"2024","author":"Cohen S","unstructured":"Cohen S, Ducharme S, Brosch JR, et al. Single ascending dose results from an ongoing Phase 1 study of mivelsiran (ALN-APP), the first investigational RNA interference therapeutic targeting amyloid precursor protein for Alzheimer\u2019s disease. Alzheimer\u2019s Dement 2024. DOI: https:\/\/doi.org\/10.1002\/alz.084521","journal-title":"Alzheimer\u2019s Dement"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00313"},{"key":"e_1_3_2_22_2","unstructured":"Sage Therapeutics. Sage therapeutics announces topline results from the Phase 2 DIMENSION study of Dalzanemdor (SAGE-718) in the treatment of cognitive impairment associated with Huntington\u2019s disease https:\/\/investor.sagerx.com\/news-releases\/news-release-details\/sage-therapeutics-announces-topline-results-phase-2-dimension (accessed 11 February 2025)."},{"key":"e_1_3_2_23_2","unstructured":"UniQure Biopharma B.V. Safety and proof-of-concept (POC) study with AMT-130 in adults with early manifest Huntington\u2019s disease."},{"key":"e_1_3_2_24_2","unstructured":"UniQure Biopharma B.V. Safety and efficacy of AMT-130 in European adults with early manifest Huntington\u2019s disease."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004743"},{"key":"e_1_3_2_26_2","unstructured":"UniQure Biopharma B.V. uniQure announces positive interim data update demonstrating slowing of disease progression in Phase I\/II trials of AMT-130 for Huntington\u2019s disease uniQure announces positive interim data update demonstrating slowing of disease progression in Phase I\/II trials of AMT-130 for Huntington\u2019s disease https:\/\/uniqure.gcs-web.com\/news-releases\/news-release-details\/uniqure-announces-positive-interim-data-update-demonstrating (accessed 14 August 2024)."}],"container-title":["Journal of Huntington's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/18796397251337000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/18796397251337000","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/18796397251337000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:56:33Z","timestamp":1777452993000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/18796397251337000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1177\/18796397251337000"],"URL":"https:\/\/doi.org\/10.1177\/18796397251337000","relation":{},"ISSN":["1879-6397","1879-6400"],"issn-type":[{"value":"1879-6397","type":"print"},{"value":"1879-6400","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,30]]}}}