Tominersen

2024 marked significant progress in Huntington’s disease (HD) research, with breakthroughs in understanding somatic instability, advancements in drug development, and both challenges and triumphs in clinical trials. The HD community saw the power of collaboration and innovation, with new voices at HDBuzz and updates from global conferences. Despite setbacks, there's hope with ongoing trials and new drug approvals, moving closer to treatments that could slow or halt HD.

Vico Therapeutics' VO659, an antisense oligonucleotide targeting C-A-G repeats in Huntington's disease (HD), shows potential to reduce toxic HD protein levels and is being tested in a basket trial for HD, SCA1, and SCA3. Initial data suggest VO659's safety and efficacy, though radiculitis side effects were observed at higher doses, prompting future dosing adjustments.

Novartis pays $1 billion upfront to license PTC518, a Huntington's disease drug, with potential for $1.9 billion in milestone payments and royalties. PTC retains 40% of U.S. profits and leads Phase 2 completion and FDA discussions. The deal is expected to close in Q1 2025.

Huntington's disease treatments face challenges due to rarity and trial failures, but recent milestones like Wave's WVE-003, Roche-Ionis' tominersen, uniQure's AMT-130, and PTC Therapeutics' PTC518 offer hope. Prilenia's pridopidine is under EMA review, while Annexon's ANX005 and Sage's dalzanemdor faced setbacks. Despite these, cautious optimism remains for effective treatments.

Day 2 of the 2024 Huntington Study Group Conference featured talks on palliative care, clinical trial challenges, and updates from various drug development companies, emphasizing the importance of early intervention and the use of biomarkers in HD treatment.

HSG 2024 in Cincinnati features updates on HD research, including MyHDStory, KINECT-HD, huntingtin-lowering debates, drug delivery, CRISPR gene editing, and innovative HD therapeutics from various companies.

Despite decades of research, Huntington’s disease lacks a disease-modifying treatment. Clinical trials face challenges due to limited patient numbers and geographic barriers. Prilenia Therapeutics, Sage Therapeutics, uniQure, Wave Life Sciences, and Roche-Ionis are developing potential treatments, though some have faced setbacks. Prilenia’s pridopidine and Sage’s dalzanemdor showed mixed results, while uniQure’s AMT-130 and Wave’s WVE-003 demonstrated promising reductions in mutant huntingtin protein. Roche-Ionis’ tominersen faces ongoing development challenges.

New Huntington's disease therapies are nearing R&D finish lines, aiming to be the first disease-modifying treatments. Despite high-profile failures, companies like Wave, Prilenia, and uniQure are progressing towards regulatory approval. The field has gained momentum after decades of trial and error, with several mid-stage clinical trials underway. The ideal therapy would selectively lower mutant huntingtin and be widely distributed in the brain, though none currently exist.

Despite failed trials, hope is renewed in Huntington's disease treatment with a gene therapy showing 80% slowing of disease progression and another treatment seeking FDA accelerated approval.