A new oral drug for Huntington's disease is turning heads. Skyhawk Therapeutics' SKY-0515 showed favorable trends across all motor, functional, and cognitive endpoints at 12 months compared to natural history expectations — and not a single patient or clinician reported disease worsening. The pivotal phase 2/3 FALCON-HD program is now actively enrolling globally.
A new oral drug for Huntington's disease is turning heads.
Skyhawk Therapeutics presented 12-month phase 1/2 data for SKY-0515 — an investigational oral RNA-splicing modifier — at the European Academy of Neurology annual meeting. The drug works on two fronts: reducing mutant huntingtin protein (mHTT) and suppressing PMS1, a protein linked to somatic CAG repeat expansion, a key driver of Huntington's disease (HD) progression. Across all four composite Unified Huntington's Disease Rating Scale (cUHDRS) subcomponents, treated patients trended favorably compared to natural history expectations — and the gap widened progressively from months 3 to 12, suggesting a compounding benefit over time.
Perhaps most striking: at 12 months, 0% of patients or clinicians reported disease worsening, while 65% of patients and 50% of clinicians reported improvement. Biomarker data also held up, with sustained reductions in blood mHTT of up to 69% and PMS1 mRNA of up to 26%.
By the Numbers:
Why it matters: Huntington's disease has no disease-modifying treatments approved to date. SKY-0515's dual-target mechanism and early clinical signals offer a potentially meaningful step forward, with a pivotal trial now actively enrolling across more than 40 sites worldwide.
