Systematic Review of the Huntington's Disease Drug Development Pipeline, 2014 to 2025.

BACKGROUND

In the past decade, significant advances have improved our understanding of the mechanisms underlying HD pathobiology leading to several putative therapeutic targets for HD.

OBJECTIVE

The aim was to describe the Huntington's disease (HD) drug development clinical pipeline.

METHODS

We analyzed all HD clinical trials described in clinicaltrials.gov and the WHO International Clinical Trials Registry from January 1, 2014, to November 13, 2025. Studies were classified as interventional (pharmacological and nonpharmacological) or observational (natural history, biomarker, and other). Interventional trials were further categorized according to phase of development and type of intervention. Proposed mechanisms of action were classified according to adapted Common Alzheimer's and Related Dementias Research Ontology definitions, with huntingtin lowering assigned as a separate category.

RESULTS

A total of 165 registered clinical studies for Huntington's disease (HD) were identified between 2014 and the index date, requiring 7501 participants. These included 54 observational studies and 111 interventional trials. Of the 69 pharmacological trials, 54.9% have been completed, 10.8% have been terminated, and 39.2% remain active. Over the past 11 years, 50 different pharmacological agents have been tested in 69 trials, with 21 agents currently being evaluated. Disease-modifying therapies now account for 90.5% of phase 1 trials, 61.8% of phase 2 trials, and 55.6% of phase 3 trials in the pipeline.

CONCLUSIONS

Over the past decade, the HD clinical trial landscape has expanded and shifted toward disease-modifying strategies, with significant changes in trial design and a shift in the target population to an earlier stage of disease. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.