{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:37:33Z","timestamp":1792708653436,"version":"4.5.0"},"reference-count":44,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"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"],"abstract":"<jats:p>In this edition, we highlight several important developments across the Huntington's disease therapeutic pipeline. We discuss the launch and subsequent discontinuation of POINT-HD, the first-in-human phase I study of RG6496 (Hoffmann-La Roche), an allele-selective antisense oligonucleotide designed to selectively lower mutant huntingtin while largely preserving wild-type huntingtin expression. We also discuss the launch of two phase III efficacy trials: INVEST-HD, evaluating votoplam (Novartis Pharmaceuticals), and PRECISE-HD, evaluating pridopidine (Prilenia). In addition, we summarise recent advances across the field, including preclinical updates for LQT-23 (LoQus23), SRP-1005 (Sarepta Therapeutics) and HRN001 (Harness Therapeutics); interim 12-month clinical results from SKY-0515 (Skyhawk Therapeutics); the announcement by uniQure that 3-year data from the phase I\/II AMT-130 study may support a Biologics License Application seeking accelerated approval and Roche's discontinuation of the phase II GENERATION HD2 study of tominersen. Finally, we provide an updated listing of registered and ongoing clinical trials in Huntington's disease.<\/jats:p>","DOI":"10.1177\/18796397261499360","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:23:30Z","timestamp":1792412610000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Huntington's disease clinical trials update: August 2026"],"prefix":"10.1177","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","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opeyemi","family":"Kinyomi","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J","family":"Wild","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,19]]},"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","doi-asserted-by":"publisher","DOI":"10.1177\/18796397251399751"},{"key":"e_1_3_3_15_2","unstructured":"Hoffmann-La Roche. A study to evaluate the safety tolerability pharmacokinetics and pharmacodynamics of RG6496 in Huntington\u2019s disease (POINT-HD) https:\/\/clinicaltrials.gov\/study\/NCT07246941 (2026 accessed 22 January 2026)."},{"key":"e_1_3_3_16_2","unstructured":"Novartis Pharmaceuticals. A study to investigate the efficacy safety and tolerability of Votoplam in participants with Huntington\u2019s disease (INVEST-HD) https:\/\/clinicaltrials.gov\/study\/NCT07326709 (2026 accessed 22 June 2026)."},{"key":"e_1_3_3_17_2","unstructured":"Pridopidine. Pridopidine Phase 3 study in Huntington\u2019s disease (PRECISE-HD) https:\/\/clinicaltrials.gov\/study\/NCT07609108 (2026 accessed 22 June 2026)."},{"key":"e_1_3_3_18_2","unstructured":"LoQus23 Therapeutics. LoQus23 Therapeutics nominates LQT-23 as first-in-class oral drug candidate for Huntington\u2019s disease https:\/\/loqus23.com\/loqus23-therapeutics-nominates-lqt-23-as-first-in-class-oral-drug-candidate-for-huntingtons-disease\/ (2026 accessed 13 January 2026)."},{"key":"e_1_3_3_19_2","unstructured":"Sarepta Therapeutics. Sarepta therapeutics announces approval of clinical trial application for SRP-1005 its investigational treatment for Huntington\u2019s disease https:\/\/investorrelations.sarepta.com\/news-releases\/news-release-details\/sarepta-therapeutics-announces-approval-clinical-trial (2026 accessed 24 June 2026)."},{"key":"e_1_3_3_20_2","unstructured":"Harness Therapeutics. Harness therapeutics nominates HRN001 a first-in-class drug candidate for Huntington\u2019s disease and establishes clinical Advisory Board https:\/\/www.harnesstx.com\/news\/harness-therapeutics-nominates-hrn001-a-first-in-class-drug-candidate-for-huntingtons-disease-and-establishes-clinical-advisory\/ (2026 accessed 24 June 2026)."},{"key":"e_1_3_3_21_2","unstructured":"Skyhawk Therapeutics Inc. Skyhawk therapeutics announces twelve-month interim results from Phase 1\/2 clinical trial of SKY-0515 in Huntington\u2019s disease https:\/\/www.skyhawktx.com\/post\/skyhawk-therapeutics-announces-twelve-month-interim-results-from-phase-1-2-clinical-trial-of-sky-051 (2026 accessed 24 June 2026)."},{"key":"e_1_3_3_22_2","unstructured":"uniQure Biopharma B.V. uniQure announces plan for BLA submission for AMT-130 in Huntington\u2019s disease https:\/\/uniqure.gcs-web.com\/node\/12796\/pdf (2026 accessed 21 June 2026)."},{"key":"e_1_3_3_23_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 (2025 accessed 11 August 2025)."},{"key":"e_1_3_3_24_2","unstructured":"Hoffmann-La Roche. Update on two clinical studies: GENERA TION HD2 (tominersen) and POINT-HD (RG6496) https:\/\/ehdn.org\/wp-content\/uploads\/2026\/07\/Roche-GENERATION-HD2-_-POINT-HD-global-patient-community-letter-July2026.pdf (2026 accessed 15 July 2026)."},{"key":"e_1_3_3_25_2","unstructured":"Hoffmann-La Roche. Frequency of selected single nucleotide polymorphisms in Huntington disease gene expansion carriers https:\/\/www.clinicaltrials.gov\/study\/NCT06667414 (2026 accessed 22 January 2026)."},{"key":"e_1_3_3_26_2","unstructured":"Hoffmann-La Roche. Roche Community Letter - 15 December 2025: \u2018New Phase 1 POINT-HD study starts for selective huntingtin-lowering approach\u2019."},{"key":"e_1_3_3_27_2","unstructured":"Novartis Pharmaceuticals. A study to evaluate the safety and efficacy of PTC518 in participants with Huntington\u2019s disease (HD) https:\/\/clinicaltrials.gov\/study\/NCT05358717 (2026 accessed 24 June 2026)."},{"key":"e_1_3_3_28_2","unstructured":"Novartis Pharmaceuticals. An extension study to evaluate the long-term safety and efficacy of Votoplam in participants with Huntington\u2019s disease https:\/\/clinicaltrials.gov\/study\/NCT06254482 (2026 accessed 24 June 2026)."},{"key":"e_1_3_3_29_2","unstructured":"PTC Therapeutics. PTC therapeutics reports positive topline results from Month 24 Interim analysis of PIVOT-HD extension study of Votoplam https:\/\/ir.ptcbio.com\/news-releases\/news-release-details\/ptc-therapeutics-reports-positive-topline-results-month-24 (2026 accessed 24 June 2026)."},{"key":"e_1_3_3_30_2","unstructured":"Prilenia. PRidopidine\u2019s outcome on function in Huntington disease PROOF- HD https:\/\/www.clinicaltrials.gov\/study\/NCT04556656 (2025 accessed 22 August 2025)."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03920-3"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30161-8"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz115"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-52667-3"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adn4600"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109649"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-025-01159-7"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg352"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp242"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.11.038"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03424-6"},{"key":"e_1_3_3_42_2","unstructured":"Skyhawk Therapeutics Inc. Study to evaluate the pharmacodynamics safety and efficacy of SKY-0515 in participants with Huntington\u2019s disease (FALCON-HD) https:\/\/clinicaltrials.gov\/study\/NCT07378644 (2026 accessed 24 June 2026)."},{"key":"e_1_3_3_43_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 (2026 accessed 12 October 2026)."},{"key":"e_1_3_3_44_2","unstructured":"uniQure Biopharma B.V. uniQure announces successful UK MHRA pre-submission meeting for AMT-130 in Huntington\u2019s disease https:\/\/uniqure.gcs-web.com\/node\/12636\/pdf (2026 accessed 25 June 2026)."},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2300400"}],"container-title":["Journal of Huntington's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/18796397261499360","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/18796397261499360","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/18796397261499360","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:46:12Z","timestamp":1792705572000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/18796397261499360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,19]]},"references-count":44,"alternative-id":["10.1177\/18796397261499360"],"URL":"https:\/\/doi.org\/10.1177\/18796397261499360","relation":{},"ISSN":["1879-6397","1879-6400"],"issn-type":[{"value":"1879-6397","type":"print"},{"value":"1879-6400","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,19]]},"article-number":"18796397261499360"}}