The last decade has brought significant developments in the field of neurodegenerative diseases. In 2023, disease-modifying therapies for Alzheimer’s and a subtype of amyotrophic lateral sclerosis (ALS) received approval. In September, uniQure reported that its gene therapy slowed progression in Huntington’s disease by 75%, raising hopes for those affected by the condition.
Huntington’s disease is a severe neurodegenerative disorder caused by a CAG repeat in the huntingtin (HTT) gene. Although this gene was identified in 1993, progress since then has been slow, with only symptomatic treatments becoming available. Several companies, including Roche, Wave Life Sciences, and Sage Therapeutics, have attempted to develop more effective therapies but have faced setbacks.
The recent data from uniQure provided optimism for about 41,000 Americans living with Huntington’s and over 200,000 more who carry the genetic mutation. UniQure had planned to submit a biologics license application (BLA) early next year. However, feedback from a pre-BLA meeting indicated that the FDA “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,” according to information revealed by the company in December.
Despite this setback for uniQure, other companies continue their efforts in a Huntington’s market expected to approach $1.9 billion by 2030.
After discontinuing a Phase III trial for tominersen—an antisense oligonucleotide (ASO)—in 2021 due to disappointing results, Roche revisited the drug based on post-hoc analysis suggesting potential benefits for younger adults with lower disease burden at low exposure levels. Tominersen is now being tested in a Phase II clinical trial targeting patients with prodromal and early manifest Huntington’s disease; completion is anticipated in spring 2027.
Wave Life Sciences also experienced difficulties in 2021 when it shelved two ASO therapies shortly after Roche’s announcement. The company has since developed WVE-003, another ASO candidate intended for a Phase II/III trial this quarter. Wave has reached an agreement with the FDA regarding accelerated approval pathways using slowing of caudate atrophy as a surrogate endpoint—a measure closely linked to reduced mutant huntingtin protein levels.
A version of this article was first published as a special edition of ClinicaSpace on November 3, 2025.
