First US patients dosed in trial of experimental Huntington’s treatment

The first U.S. participants has been dosed in the global portion of a clinical trial program testing if Skyhawk Therapeutics’ experimental therapy SKY-0515 can slow the progression of Huntington’s disease.

The global portion (NCT07378644) of the Phase 2/3 trial program, called FALCON-HD, is enrolling up to 400 adults, ages 25 and older, with early-stage Huntington’s at sites across North America, Europe, and South America.

The first U.S. participants were dosed at CenExel Movement Disorder Center in Denver. Other U.S. sites, including the Beth Israel Deaconess Medical Center in Boston, will soon begin dosing as well, according to Skyhawk.

“The opening of U.S. sites in the pivotal FALCON-HD study is an important milestone for the U.S. Huntington’s disease community, where there are still no approved therapies shown to slow the progression of the disease,” Samuel Frank, MD, an investigator on the FALCON-HD program at Beth Israel Deaconess, said in a press release from Skyhawk. “We look forward to beginning dosing at Beth Israel Deaconess before end of 2026 and to offering eligible people with HD in the U.S. the opportunity to take part in this study.”

In addition to the worldwide portion, the pivotal FALCON-HD program includes an Australian and New Zealand (ANZ) portion (NCT06873334) that has finished enrollment of nearly 150 patients ahead of schedule. Pivotal trial programs are designed to provide robust data that, if positive, could be used as a basis to apply for a therapy’s regulatory approval.

“More than 50,000 doses of SKY-0515 have been administered to date, across more than 30 study sites in 10 countries,” the release stated.

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Data from earlier trial show SKY-0515 works on proteins as designed

Huntington’s is caused by mutations in the HTT gene, leading to the production of a mutant version of the huntingtin (HTT) protein. The mutant protein is thought to damage cells in the brain and ultimately drive the disease.

When genes are read to produce protein, the genetic code is transcribed into a temporary molecule called messenger RNA (mRNA), which is then used as a template for protein production.

SKY-0515 is a once-daily oral therapy designed to target the HTT gene’s mRNA, thereby reducing production of both normal and mutant forms of the HTT protein. The therapy also targets the mRNA of the PMS1 gene, which encodes a DNA-repair protein of the same name that has been implicated in Huntington’s development and progression.

Data from early-stage Huntington’s patients participating in a previous Phase 1/2 clinical trial (ACTRN12624000602527) showed that SKY-0515 works on HTT and PMS1 as designed.

SKY-0515 is designed to lower both mutant huntingtin and PMS1, two proteins implicated in [Huntington’s disease biology] and progression, and the Phase 1/2 results to date have been very encouraging.

Also, after a year on the therapy, patients’ scores on the Composite Unified Huntington’s Disease Rating Scale (cUHDRS), a validated measure of disease progression, were better than they had been at the study’s start. This contrasts with the typical, progressive course of the disease. SKY-0515 also showed an acceptable safety profile.

“SKY-0515 is designed to lower both mutant huntingtin and PMS1, two proteins implicated in [Huntington’s disease biology] and progression, and the Phase 1/2 results to date have been very encouraging,” Frank said.

In the FALCON-HD program, participants are randomly assigned to take daily SKY-0515 at one of three doses, or a placebo, for up to about 1.5 years. The main goal of the worldwide portion is to see if SKY-0515 can slow Huntington’s progression, as measured by the cUHDRS. This is also one of the main goals of the ANZ portion.

The ANZ portion is anticipated to be completed by the end of next year, while the worldwide portion is anticipated to end in 2029.

“Bringing FALCON-HD to the U.S. is an important step toward our goal of delivering a once-daily oral, potentially disease-modifying treatment to people living with Huntington’s disease,” said Bill Haney, co-founder and CEO of Skyhawk. “We are grateful to the participants, families and investigators whose commitment is making this study possible.”