Breakthrough in Huntington's Disease Treatment Sparks New Wave of Therapies
In a groundbreaking development for the Huntington's disease (HD) community, recent clinical trial results have reignited hope for effective treatments. This surge of progress comes after years of setbacks, with several pharmaceutical companies now racing to bring disease-modifying therapies to market.
UniQure's Gene Therapy Leads the Pack
Dutch biotech uniQure has reported "historic positive results" from a pivotal trial of its gene therapy, AMT-130. The three-year data showed a 75% slowdown in disease progression among 29 patients, marking the first successful treatment of Huntington's disease. Despite the small sample size and the invasive nature of the 12-18 hour intracranial surgery required, experts hail these results as a significant milestone not just for HD but for the entire field of neurodegeneration.
UniQure plans to submit a biologics license application to the FDA in the first quarter of 2026, aiming to launch the first genetic treatment for Huntington's later that year.
Competing Therapies in Late-Stage Development
Wave Life Sciences' Antisense Oligonucleotide
After shelving two previous candidates, Wave Life Sciences is advancing WVE-003, an antisense oligonucleotide (ASO) targeting mutant huntingtin (mHTT) mRNA. In the Phase Ib/IIa SELECT-HD trial, WVE-003 demonstrated a 46% reduction in mHTT levels in patients' cerebrospinal fluid after 24 weeks of treatment.
Wave has reached an agreement with the FDA on a path to accelerated approval, using slowing of caudate atrophy as a clinical surrogate endpoint. The company is poised to submit an investigational new drug application for a potentially registrational Phase II/III trial.
Prilenia Therapeutics' Small Molecule Approach
Despite setbacks, including a rejection from the European Medicines Agency, Prilenia Therapeutics continues to develop pridopidine, a small molecule agonist of the sigma-1 receptor. New analyses of two-year data from the PROOF-HD study show significant slowing of disease progression in patients not taking antidopaminergic medicines.
Prilenia, in collaboration with Ferrer, plans to initiate a global confirmatory trial of pridopidine in early-stage HD patients in the first half of 2026.
PTC Therapeutics and Novartis' Blood-Brain Barrier Penetrant
PTC518, a small molecule developed by PTC Therapeutics and backed by a $2.9 billion investment from Novartis, has shown promise in reducing mHTT levels. In the Phase II PIVOT-HD trial, the lowest dose of PTC518 lowered blood HTT protein levels by 23% in both earlier- and later-stage patients.
While questions remain about the correlation between huntingtin reductions and clinical benefit, particularly in later-stage patients, analysts believe the data may be sufficient for discussions with the FDA regarding a registrational path for less advanced disease.
References
- 4 Huntington’s Therapies Chasing UniQure
Last month, “historic positive results” from uniQure’s gene therapy snapped the Huntington’s community out of years of failure. As the biotech prepares to submit for FDA approval, BioSpace looks at four more candidates on the near horizon.
Explore Further
What are the safety considerations and potential risks associated with the invasive intracranial surgery required for AMT-130's administration?
How does Wave Life Sciences plan to leverage the use of caudate atrophy as a clinical surrogate endpoint for accelerated FDA approval?
What are the differentiating factors between pridopidine and other disease-modifying therapies targeting Huntington's disease?
What steps are being taken to address uncertainties regarding the correlation between huntingtin protein reduction and clinical benefits in patients treated with PTC518?
What is the current competitive landscape for Huntington's disease treatments, and how might these emerging therapies impact it?