Pridopidine

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.

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.

Despite challenges, the HEALEY ALS Platform Trial continues with optimism, as Clene Nanomedicine and Prilenia Therapeutics progress their ALS treatments based on positive secondary endpoint data. The trial, initiated by a $40 million donation from Sean Healey and AMG, aims to efficiently test multiple therapies simultaneously. While primary endpoints have not been met, the trial's design allows for quick identification of non-viable treatments, and positive outcomes in subgroups have supported further development for some candidates.

Pridopidine, tested in multiple HD trials, has consistently failed to meet primary endpoints, despite Prilenia's mixed messaging. The drug's intended use has shifted from movement control to disease modification, with inconsistent results. Prilenia's recent press releases about regulatory submission should be interpreted cautiously, as acceptance for review is a standard step in the approval process. HDBuzz emphasizes the importance of accurate reporting and the distinction between hope and hype.

EMA to review Prilenia's pridopidine for Huntington's disease, based on clinical data showing potential to slow progression. Pridopidine, with orphan drug status in EU and US, aims to offer a new therapeutic approach. Phase 2 trial showed efficacy, while Phase 3 trial results were mixed, with potential benefits in specific subgroups.