Momentum is building in Huntington’s disease research as Skyhawk Therapeutics’ oral drug has shown early signs of motor and functional improvements in patients, following the Food and Drug Administration's recent clearance for uniQure to apply for accelerated approval of its gene therapy. Skyhawk revealed on June 30 functional data from a Phase 1/2 trial, reporting “favorable and consistent trends” on all composite Unified Huntington’s Disease Rating Scale components for patients treated with SKY-0515 compared to natural history controls after 12 months.
Skyhawk CEO Bill Haney said prior to the presentation, “We would all be grateful for just slowing the rate of decline, but to see better is very uncommon and encouraging.” The company first reported these results on June 1 and expanded on them at the European Academy of Neurology 2026 Congress. Treatment with SKY-0515 led to dose-dependent reductions in mutant huntingtin protein by up to 69% and PMS1 mRNA by up to 26%, according to Skyhawk.
Haney also pointed out that patient and physician surveys were positive: no patients in Skyhawk’s trial reported worsening disease over a year, while 65% said they got better. Physicians agreed that none of their patients worsened, with half seeing notable improvement. Haney said, “We find that very encouraging in a context in which alternative ways to treat Huntington’s take 24 months or 36 months to be effective.”
SKY-0515 is an orally administered investigational small molecule RNA splicing modifier with what Haney described as an “extraordinary” safety profile. He contrasted this approach with therapies delivered directly into the brain, such as uniQure’s AMT-130 gene therapy. Haney added that SKY-0515 has a short half-life of about 30 hours.
The FDA reversed its previous position regarding uniQure's gene therapy after six months of debate involving former agency officials. The agency now agrees existing data are sufficient for an accelerated application for AMT-130, allowing uniQure to submit its filing soon. Haney said he admires the FDA's willingness, "to reopen something that they had closed," calling it "very encouraging about the focus on patients." He added that discussions have begun with regulators about potentially accelerating approval timelines for SKY-0515 based on similar standards.
