Product information and disease descriptionPlace of product in therapyApproaches to treatmentCurrent treatment options and standard of care
Limitations of current therapies
6 evidence topics · 16 sources
Summary
Current therapies are symptomatic. No approved therapy delays onset or slows progression, and a Cochrane review of 8 trials involving 1,366 participants found no pharmacological intervention effective as a disease-modifying therapy. Only chorea has FDA-approved treatments. All three approved VMAT2 inhibitors carry boxed warnings for depression and suicidality: in the tetrabenazine placebo-controlled trial, depression or worsening depression was reported in 10 of 54 participants (19%) versus 0 of 30 receiving placebo, and tetrabenazine is contraindicated in untreated or inadequately treated depression, a common feature of the disease. Chorea benefit does not persist after discontinuation; scores returned to baseline 1 to 2 weeks after stopping tetrabenazine, deutetrabenazine, and valbenazine. The tetrabenazine label reports no difference from placebo on functional capacity and cognition, with a nominally significant decrement on one functional measure, and valbenazine labeling states that drug-induced parkinsonism can cause more functional disability than untreated chorea in some patients. Antipsychotics, antidepressants, and rehabilitation are used largely on the basis of expert consensus: the MDS review found no eligible evidence for treatments of depression, psychosis, irritability, apathy, or suicidality, or for physiotherapy, occupational therapy, exercise, or dietary interventions, and a systematic review identified 15 eligible studies of neuropsychiatric treatment. Guidelines differ on the first-line antichoreic agent (tetrabenazine in EHDN guidance; tiapride in DGN guidance), and no blinded head-to-head comparison is available. Investigational huntingtin-lowering therapies have not yet produced an approved product: tominersen phase 3 dosing was discontinued in 2021, and in an ad hoc week 69 analysis of the 791-participant GENERATION HD1 trial the cUHDRS change with the every-8-week regimen was significantly worse than with placebo (-0.54 points; adjusted P=0.001), with more adverse events than in the placebo and every-16-week groups; pridopidine missed its phase 3 primary endpoint and received a negative CHMP opinion in 2025, and after a January 2026 Type A meeting the FDA stated that AMT-130 phase I/II data compared with an external control were not sufficient as primary evidence of effectiveness before later agreeing to accept a BLA for accelerated approval.