Trial reportNature medicine2026
Oral splicing modulator branaplam in Huntington's disease: a phase 2 randomized controlled trial.
Trial report in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05111249 (A Randomized, Double-Blind, Placebo-Controlled Dose Range Finding Study With Open-Label Extension to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of LMI070/Branaplam Administered as Weekly Oral Doses in Participants With Early Manifest Huntington's Disease), which is not on this map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo-Controlled Dose Range Finding Study With Open-Label Extension to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of LMI070/Branaplam Administered as Weekly Oral Doses in Participants With Early Manifest Huntington's Disease
Who cites it
2 citing papers in PubMed.
- Specificity and exon target space of splicing modifying compounds.Nature communications · 2026Article
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lowering mutant huntingtin (HTT) gene products is a promising approach for slowing the progression of Huntington's disease (HD), a monogenic neurodegenerative disease caused by an expansion mutation in the HTT gene (NCBI Gene ID: 3064). Branaplam, an orally available HTT messenger RNA splicing modulator, reduces HTT protein levels in vitro and in animal models, and is the first splicing modulator to be evaluated in individuals with HD. Here we present the design and results of VIBRANT-HD, a randomized phase 2b study of branaplam in HD, along with preclinical findings in nonhuman primates. VIBRANT-HD utilized an innovative study design informed by our preclinical data, including targeted safety monitoring measures (for example, neurofilament light chain measurements in blood, nerve conduction studies), and staggered cohorts to capture potential neurotoxic effects early. Of the 21 participants in the initial cohort receiving branaplam 56 mg weekly, 18 (85.7%) showed at least one sign or symptom of peripheral neuropathy. This safety signal, along with dose-modeling results triggered the early termination of VIBRANT-HD. The primary outcome, a decrease in cerebrospinal fluid mutant HTT levels versus placebo, was summarized descriptively, making branaplam the first splicing modulator to lower mutant HTT levels in the cerebrospinal fluid of individuals with HD. Increased neurofilament light chain levels observed in most participants reversed after treatment discontinuation. ClinicalTrials.gov identifier: NCT05111249.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.