Vico Therapeutics Reports Positive Phase 1/2a Data for VO659 in Huntington's Disease Treatment

Vico Therapeutics B.V., a clinical-stage genetic medicines company specializing in treatments for severe neurological diseases, has announced promising interim results from an ongoing Phase 1/2a clinical trial for VO659. This investigational antisense oligonucleotide (ASO) therapy targets Huntington’s disease (HD) and other polyglutamine diseases, such as spinocerebellar ataxia types 1 and 3 (SCA1 and SCA3). The data were showcased in an oral presentation at the European Huntington’s Disease Network's EHDN & Enroll-HD 2024 meeting.

VO659’s novel approach involves targeting the CAG repeat expansions in mutant mRNA transcripts, which underlie the pathology of HD and similar disorders. By inhibiting mRNA translation, the therapy aims to decrease the production of the mutant protein, potentially halting or slowing disease progression. VO659 stands out as the only clinical-stage treatment that directly addresses the CAG repeat expansions causing HD.

The multi-center, open-label, multiple ascending dose study is designed to evaluate the safety and tolerability of four intrathecal doses of VO659, administered every four weeks to participants with early-stage HD or mild to moderate SCA1 or SCA3. The trial also measures exploratory endpoints such as pharmacodynamic (PD) biomarkers in cerebrospinal fluid (CSF), pharmacokinetics, and clinical outcomes. The interim analysis focused on safety, tolerability, and PD data for HD participants in the 40 mg cohort up to day 85 of the study.

The interim results revealed a 28% mean reduction in CSF mutant huntingtin protein (mHTT) at day 85 compared to baseline, with the effect noticeable after the first dose at day 29. Importantly, there was no sustained increase in neurofilament light chain (Nf-L) protein levels in CSF. VO659 was generally well tolerated at the 40 mg dose level, with no significant safety concerns reported. The therapy's long half-life suggests that future dosing regimens could be as infrequent as once or twice a year.

Micah Mackison, the CEO of Vico Therapeutics, expressed optimism about the results, noting the immediate reductions in CSF mHTT and the unchanged Nf-L protein levels, both critical biomarkers for HD. Mackison highlighted the potential for a less frequent dosing schedule due to VO659's long half-life. He emphasized that the data mark a significant milestone for both the company and the HD community, which urgently needs new treatment options.

The interim clinical data build on preclinical research that demonstrated VO659’s strong target engagement in various disease models. Preclinical studies showed significant, dose-dependent reductions in mHTT and improvements in motor function in HD mouse models, as well as allele-preferential reductions in mHTT in HD patient cell models.

Dr. Scott Schobel, Chief Medical Officer at Vico, praised VO659's unique allele-preferential mechanism and its direct targeting of CAG repeat expansions. He pointed out that the interim data strengthen the evidence supporting VO659's continued clinical development for HD and its broader potential applications for other CAG repeat expansion diseases.

The Phase 1/2a trial is ongoing, and Vico plans to consult with regulatory authorities later this year to determine the optimal development pathway for VO659. Updates from the SCA1 and SCA3 patient cohorts are expected to be presented at future scientific meetings.

Huntington's disease is a rare, progressive neurodegenerative disorder characterized by movement disorders, cognitive decline, and psychiatric symptoms. It is caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which leads to the production of a toxic mutant HTT protein. Current treatments mainly address symptoms, leaving a significant unmet need for therapies that can modify the disease course.

VO659 aims to suppress the mutant HTT protein in an allele-preferential manner, potentially slowing or halting disease progression. The therapy has received Orphan Drug designation from both the FDA and EMA for the treatment of HD, underscoring its potential importance in addressing this devastating condition.