Huntington’s disease RNA-splicing drug improves function and motor symptoms after 15 months

A Huntington’s disease treatment being developed by Skyhawk Therapeutics improved measures of function, cognition and motor skills after 15 months of treatment.

According to BioPharma Dive on the 15th (local time), Boston-based biotech company Skyhawk Therapeutics released final results from a small clinical trial of an oral RNA-splicing drug taken once daily.

After taking the drug for 15 months, patients with Huntington’s disease had an average 0.94-point improvement on a scale that combines assessments of function, cognition and motor skills. Over the same period, an untreated comparison group in a natural-history database worsened by an average of 0.65 points, for a 1.59-point difference between the groups.

Some neurology researchers have estimated that a 1.2-point change on this scale is “clinically meaningful.”

Skyhawk said the drug was generally well tolerated and that no serious adverse events were reported. At the higher dose, it sustained a reduction of more than 60% in mutant huntingtin protein, a primary cause of the disease.

The drug, code-named SKY-0515, is currently being evaluated in two large clinical trials, one of which has completed enrollment.

Skyhawk emerged from stealth in early 2018 with an $8 million seed investment (about 10.7 billion won). It later closed a $133 million financing round (about 178.2 billion won) in 2021 led by Fidelity Management & Research.

The company aims to develop small-molecule drugs that correct RNA expression. In Huntington’s disease, a mutation produces defective huntingtin protein that damages nerve cells.

SKY-0515 is designed to suppress not only huntingtin production but also PMS1, a protein that repairs DNA. According to Skyhawk, at the higher dose, PMS1 messenger RNA levels remained 25% lower throughout the study.

The company said the SKY-0515 group fared better than the comparison group at all major time points—3, 6, 9, 12 and 15 months—and showed a statistically significant difference beginning at 9 months.

The late-stage program, FALCON, is also underway. One trial enrolled 144 patients with stage 2 or 3 Huntington’s disease in Australia and New Zealand, while a separate global study is recruiting additional participants with a target enrollment of about 600.