A recent FDA reversal sparked new hope for patients with Huntington’s disease. Flying under the radar, Skyhawk Therapeutics revealed 12-month functional data from a midstage trial of its own candidate showing improvements on a key disease measurement scale.
Momentum is mounting again in Huntington’s disease. Two weeks after the FDA cleared uniQure to apply for accelerated approval of its gene therapy, Skyhawk Therapeutics’ oral drug has shown early signs of motor and functional improvements in patients with the intractable neurodegenerative disease.
Skyhawk revealed functional data from a Phase 1/2 trial on Tuesday, showing “favorable and consistent trends” on all composite Unified Huntington’s Disease Rating Scale (cUHDRS) components for patients treated with SKY-0515 compared to natural history controls after 12 months, according to the company’s press release. The cUHDRS assesses cognitive, motor and functional impairment in patients with Huntington’s. For the functional and motor scores specifically, patients taking Skyhawk’s drug actually saw improvement.
“We would all be grateful for just slowing the rate of decline,” Skyhawk CEO Bill Haney told BioSpace prior to the presentation, “but to see better is very uncommon and encouraging.”
For context, a single dose of uniQure’s gene therapy AMT-130 slowed disease progression by 75% after three years on the cUHDRS scale as compared to matched external controls.
Skyhawk first reported the 12-month results on June 1 but expanded on them at the European Academy of Neurology 2026 Congress on Tuesday.
Treatment with SKY-0515 also led to dose-dependent reductions in the mutant huntingtin (mHTT) protein—the primary protein driving Huntington’s disease—of up to 69% as well as reductions of up to 26% in PMS1 mRNA, Skyhawk reported. PMS1 is a key driver of somatic CAG repeat expansion associated with Huntington’s disease progression, according to Skyhawk.
Also encouraging to Haney were the results of physician and patient surveys. In a year’s time, Huntington’s disease typically causes considerable symptomatic worsening, Skyhawk said in its release. No patients in Skyhawk’s trial, on the other hand, said their disease worsened, while 65% said they got better. Their physicians largely agreed, with all doctors reporting that none of their patients got worse “and 50% got notably better,” according to Haney.
“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,” he said. “To be in that good position at 12 months is very encouraging.”
This feedback is also meaningful, Haney noted, because people with Huntington’s are unfortunately well aware of the disease process. Huntington’s is a genetic disease so many trial participants have borne witness to the ravages of the disease in their parents, which Haney said “must be so scary.”
Haney added that SKY-0515, an orally administered investigational small molecule RNA splicing modifier, has a safety profile that “looks extraordinary” and is “patient-friendly.”
“Many people are scared of the alternative approaches to getting Huntington’s therapy,” he said, specifically mentioning those delivered intrathecally, or directly to the brain, which would apply to uniQure’s AMT-130.
Not only is SKY-0515 a pill, but it has a 30-hour half-life, meaning it doesn’t stick around long in the body, Haney explained. Putting himself in the shoes of a patient with Huntington’s, he said he would choose a drug like that over a more complex therapy.
Flying faster toward approval?
Thirty-three years after the discovery of the HTT gene that underlies Huntington’s, there have been precious few advances in the treatment of the intractable disease.
Patients and researchers celebrated in September 2025 when uniQure reported three-year data showing a 75% slowing of disease progression. The company pledged at that time to file for FDA approval in the first quarter of 2026.
Weeks later, however, the FDA reversed course on previous guidance, telling uniQure it “no longer agree[d]” that data from the Phase 1/2 trial would be “adequate to provide the primary evidence in support of a BLA submission.” Instead, the FDA insisted on a sham surgery–controlled Phase 3 study.
Six months of drama ensued, with former FDA commissioner Marty Makary and CBER director Vinay Prasad each speaking out against the therapy in the press. But after both men departed the agency this spring, the FDA reversed course and agreed that uniQure’s existing data would be sufficient to support an accelerated application for AMT-130. UniQure plans to submit this filing in the third quarter.
“I really admire the FDA for being willing to reopen something that they had closed,” Haney said, adding that this isn’t the case with all people or organizations. “To me that says something very encouraging about the focus on patients.”
Skyhawk has enrolled more than 140 patients in the pivotal placebo-controlled Phase 2/3 FALCON-HD study of SKY-0515, but Haney said the company has had discussions with the FDA about a potentially accelerated timeline.
“I have to believe that the FDA, applying the same standards to us that they apply to uniQure, will be welcoming of an accelerated approval, and with an appropriately robust confirmatory study,” Haney said. “They are encouraging us to look for the fastest way we can move responsibly for patients, and we want to do that.”
