Recent breakthroughs and three decades of progress in treating Huntington’s disease
The past 10 years have seen landmark moments for several neurodegenerative conditions. From the 2023 approvals of disease-modifying therapies for Alzheimer’s and a subtype of amyotrophic lateral sclerosis (ALS) to uniQure’s data in September showing that its gene therapy slowed progression in Huntington’s by 75%, the sector has seemingly begun to break through in these intractable diseases.
Families with Huntington’s need this to be true more than most. The devastating neurodegenerative disease is caused by a CAG repeat in the first exon of the huntingtin (HTT) gene. While this gene was first discovered in 1993, the ensuing 32 years have seen a trickle of incremental progress, with only symptomatic treatments emerging as candidates by Roche, Wave Life Sciences, Sage Therapeutics and more failed to effectively conquer the disease itself.
September’s readout by uniQure sparked new hope for the approximately 41,000 Americans living with Huntington’s—and over 200,000 more who carry the genetic mutation. While uniQure was full speed ahead with plans to submit a biologics license application early next year, the FDA has seemingly reversed position on the therapy. Feedback from a pre-BLA meeting revealed by the company in December indicated the agency “no longer agrees” that data from its Phase I/II trials would be “adequate to provide the primary evidence in support of a BLA submission.”
However, the Dutch biotech is hardly alone in a Huntington’s market that is projected to reach nearly $1.9 billion by 2030.
Resilient Pipeline
After Roche and Ionis stopped a Phase III trial in 2021 for their antisense oligonucleotide (ASO) tominersen, Roche revitalized the asset based on a post-hoc analysis showing that low-exposure of the drug may benefit younger adult patients with lower disease burden. Tominersen is now being investigated in a Phase II clinical trial for patients with prodromal and early manifest Huntington’s. That trial is expected to be completed in spring 2027.
2021 was also a bad year for Wave, which shelved two ASO therapies a week after Roche’s unfortunate news. But Wave is back too, with a next-generation ASO called WVE-003 that the company plans to take into a Phase II/III trial this quarter. The Cambridge, Mass.–based biotech has also aligned with the FDA on a path to accelerated approval, using the slowing of caudate atrophy—which has been strongly linked to a reduction in mutant huntingtin protein—as a clinical surrogate endpoint.
Editor’s note: A version of this article was originally published as a special edition of ClinicaSpace on Nov. 3, 2025.
