{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:52:08Z","timestamp":1793069528758,"version":"4.5.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"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":[[2026,2]]},"abstract":"<jats:p>In this edition of the Huntington's Disease Clinical Trials Update, we expand on the launch of the phase II\/III clinical trial of SKY-0515 from Skyhawk Therapeutics and the phase I\/II clinical trial of SPK-10001 from Spark Therapeutics. We also report positive topline data from uniQure's phase I\/II clinical trial of AMT-130 after 36 months of follow-up. Further updates include recent developments in Roche's tominersen programme within GENERATION HD2, progress with votoplam (PTC518) in PIVOT-HD by PTC Therapeutics and developments in the collaborative PTC Therapeutics\/Novartis programme. We additionally discuss regulatory developments regarding pridopidine following the negative PROOF-HD study. Finally, we provide an updated listing of all registered and ongoing clinical trials in Huntington's disease.<\/jats:p>","DOI":"10.1177\/18796397251399751","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:08:06Z","timestamp":1764169686000},"page":"156-166","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Huntington's disease clinical trials update: October 2025"],"prefix":"10.1177","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0679-0117","authenticated-orcid":false,"given":"Mena","family":"Farag","sequence":"first","affiliation":[{"name":"UCL Queen Square Institute of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J","family":"Wild","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-170262"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-189001"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-189003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-190001"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-199003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-200002"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-229002"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-229006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-239001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-240017"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/18796397241293955"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/18796397251337000"},{"key":"e_1_3_3_14_2","unstructured":"Skyhawk Therapeutics Inc. Study of SKY-0515 for safety efficacy and pharmacodynamics in participants with Huntington\u2019s disease (Falcon-HD) https:\/\/clinicaltrials.gov\/study\/NCT06873334 (accessed 11 August 2025)."},{"key":"e_1_3_3_15_2","unstructured":"Spark Therapeutics Inc. A randomized study of SPK-10001 gene therapy in participants with Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT06826612 (accessed 14 August 2025)."},{"key":"e_1_3_3_16_2","unstructured":"uniQure Biopharma B.V. Safety and proof-of-concept (POC) study with AMT-130 in adults with early manifest Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT04120493 (accessed 22 August 2025)."},{"key":"e_1_3_3_17_2","unstructured":"uniQure Biopharma B.V. Safety and efficacy of AMT-130 in European adults with early manifest Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT05243017 (accessed 22 August 2025)."},{"key":"e_1_3_3_18_2","unstructured":"Hoffmann-La Roche. GENERATION HD2. A study to evaluate the safety biomarkers and efficacy of tominersen compared with placebo in participants with prodromal and early manifest Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT05686551 (accessed 11 August 2025)."},{"key":"e_1_3_3_19_2","unstructured":"PTC Therapeutics. A study to evaluate the safety and efficacy of PTC518 in participants with Huntington\u2019s disease (HD) https:\/\/clinicaltrials.gov\/study\/NCT05358717 (accessed 11 August 2025)."},{"key":"e_1_3_3_20_2","unstructured":"PTC Therapeutics. An extension study to evaluate the long-term safety and efficacy of PTC518 in participants with Huntington\u2019s disease (HD) https:\/\/clinicaltrials.gov\/study\/NCT06254482 (accessed 11 August 2025)."},{"key":"e_1_3_3_21_2","unstructured":"Prilenia. Pridopidine\u2019s outcome on function in Huntington disease PROOF- HD https:\/\/www.clinicaltrials.gov\/study\/NCT04556656 (accessed 22 August 2025)."},{"key":"e_1_3_3_22_2","unstructured":"Skyhawk Therapeutics Inc. A phase I randomised double blind placebo-controlled single and multiple ascending dose study to evaluate the safety tolerability pharmacokinetics pharmacodynamics and effect of food on the bioavailability of SKY-0515 in healthy volunteers https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=386527 (accessed 11 August 2025)."},{"key":"e_1_3_3_23_2","unstructured":"Skyhawk Therapeutics Inc. Skyhawk therapeutics announces positive topline results of SKY-0515 as a treatment for Huntington\u2019s disease reaching 72% Huntingtin mRNA reduction https:\/\/www.skyhawktx.com\/post\/skyhawk-therapeutics-announces-positive-topline-results-from-parts-a-and-b-of-its-phase-1-clinical-t (2024 accessed 11 August 2025)."},{"key":"e_1_3_3_24_2","unstructured":"Skyhawk Therapeutics Inc. Skyhawk therapeutics announces positive first interim results in patients from its phase 1 clinical trial of SKY-0515 as a treatment for Huntington\u2019s disease https:\/\/www.skyhawktx.com\/post\/skyhawk-therapeutics-announces-positive-first-interim-results-in-patients-from-its-phase-1-clinical (2025 accessed 25 September 2025)."},{"key":"e_1_3_3_25_2","unstructured":"Skyhawk Therapeutics Inc. Skyhawk therapeutics announces first patient dosed in phase 2\/3 FALCON-HD trial of SKY-0515 for Huntington\u2019s disease https:\/\/www.skyhawktx.com\/post\/skyhawk-therapeutics-announces-first-patient-dosed-in-phase-2-3-falcon-hd-trial-of-sky-0515-for-hunt (2025 accessed 11 August 2025)."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03424-6"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.11.038"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2024.04.015"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.01.031"},{"key":"e_1_3_3_30_2","doi-asserted-by":"crossref","unstructured":"Abstracts of the 31st annual meeting of the Huntington Study Group\u00ae November 7-9 2024. J Huntingtons Dis 2024; 13: S1\u2013S56.","DOI":"10.3233\/JHD-249004"},{"key":"e_1_3_3_31_2","unstructured":"CHDI Foundation. CHDI\u2019s 20th annual HD therapeutics conference February 24-27 2025 Palm Springs California https:\/\/chdifoundation.org\/2025-conference\/ (2025 accessed 29 September 2025)."},{"key":"e_1_3_3_32_2","unstructured":"Roche-Spark HD community letter - 12 June 2025 https:\/\/hdsa.org\/wp-content\/uploads\/2025\/06\/Roche-Spark-HD-Community-Letter-June-2025.pdf (2025 accessed 21 August 2025)."},{"key":"e_1_3_3_33_2","unstructured":"uniQure Biopharma B.V. uniQure announces positive topline results from pivotal phase I\/II study of AMT-130 in patients with Huntington\u2019s disease https:\/\/uniqure.gcs-web.com\/node\/12261\/pdf (2025 accessed 27 September 2025)."},{"key":"e_1_3_3_34_2","unstructured":"Roche GENERATION HD2 community letter - 17 April 2025 https:\/\/hdsa.org\/wp-content\/uploads\/2025\/04\/April-2025-Roche-GENERATION-HD2-Community-Letter.pdf (2025 accessed 21 August 2025)."},{"key":"e_1_3_3_35_2","unstructured":"Hoffmann-La Roche. A study to evaluate the efficacy and safety of intrathecally administered RO7234292 (RG6042) in participants with manifest Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT03761849 (accessed 21 August 2025)."},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2300400"},{"key":"e_1_3_3_37_2","unstructured":"PTC Therapeutics. PTC518 PIVOT-HD study achieves primary endpoint https:\/\/ir.ptcbio.com\/news-releases\/news-release-details\/ptc518-pivot-hd-study-achieves-primary-endpoint (2025 accessed 21 August 2025)."},{"key":"e_1_3_3_38_2","unstructured":"Novartis HD community letter - 15 July 2025 https:\/\/hdsa.org\/wp-content\/uploads\/2025\/08\/Novartis-HD-Community-Letter-August-2025.pdf (2025 accessed 22 August 2025)."},{"key":"e_1_3_3_39_2","unstructured":"Prilenia and Ferrer provide update on European regulatory process for pridopidine in Huntington\u2019s Disease https:\/\/news.prilenia.com\/press-releases\/press-release-details\/2025\/Prilenia-and-Ferrer-Provide-Update-on-European-Regulatory-Process-for-Pridopidine-in-Huntingtons-Disease\/default.aspx (2025 accessed 22 August 2025)."}],"container-title":["Journal of Huntington's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/18796397251399751","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/18796397251399751","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/18796397251399751","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:56:40Z","timestamp":1777453000000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/18796397251399751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1177\/18796397251399751"],"URL":"https:\/\/doi.org\/10.1177\/18796397251399751","relation":{},"ISSN":["1879-6397","1879-6400"],"issn-type":[{"value":"1879-6397","type":"print"},{"value":"1879-6400","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}