A Dose Range Finding Study With Open-Label Extension to Evaluate the Safety of Oral LMI070/Branaplam in Early Manifest Huntington's Disease

Summary

This is the first study of branaplam in adults with Huntington's Disease (HD) to determine the correct dose required to lower mutant huntingtin protein (mHTT) levels in the cerebrospinal fluid (CSF) to a degree expected to be efficacious over longer periods of time.

Timeline

Start

2021-12-08

Primary completion

2023-10-27

Completion

2023-10-27

Outcome

Results reported · no primary-endpoint met/missed verdict (typical of a dose-finding / safety study)

Stopped: “The trial was halted prematurely due to signs and symptoms that suggested the possibility of peripheral neuropathy. All participants who received branaplam continued to undergo routine (safety) evaluations for up to a year following their final dose”

paper The primary outcome, a decrease in cerebrospinal fluid mutant HTT levels versus placebo, was summarized descriptively PMID 41491108 ↗

Publications

• Borowsky B, Ramos H, Caputo A, Hartmann A, Faller T, Peters T, Sui Y, Liu F, Meadowcroft M, David OJ, Laisney M, Kinhikar A, Marder KS, Tabrizi SJ, Landwehrmeyer GB, Leavitt BR. Oral splicing modulator branaplam in Huntington's disease: a phase 2 randomized controlled trial. Nat Med. 2026 Jan;32(1):103-112. doi: 10.1038/s41591-025-04117-4. Epub 2026 Jan 5.
• Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017.
• Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Branaplam	Small molecule	28 mg	Oral
Subject	Branaplam	Small molecule	56 mg	Oral
Subject	Branaplam	Small molecule	84 mg	Oral
Subject	Branaplam	Small molecule	112 mg	Oral
Subject	Branaplam	Small molecule	154 mg	Oral

Indications