Gene therapy for Bietti crystalline corneoretinal dystrophy: A phase 1/2 clinical trial.

Bietti crystalline corneoretinal dystrophy (BCD) is an inherited retinal degeneration caused by bi-allelic variants in the CYP4V2 gene. Here, we report a phase 1/2, dose-escalation clinical study to assess the safety and efficacy of ZVS101e, an adeno-associated viral (AAV)-mediated gene-augmentation therapy (rAAV2/8-hCYP4V2), in 11 BCD patients with up to 365 days of follow-up (NCT05832684). ZVS101e showed a favorable safety profile, with no dose-limiting toxicities or drug-related serious adverse events. Inflammatory response was observed, primarily in the medium- and high-dose groups, which were effectively managed with corticosteroids. Efficacy was optimal in the low-dose group, with mean best-corrected visual acuity improvement of 14.0 letters and 50% of participants achieving clinically meaningful gains (≥15 letters). Functional assessments, including a multi-luminance mobility test and Visual Function Questionnaire-25, along with retinal structure, demonstrated consistent improvements. These results highlight ZVS101e's therapeutic potential for BCD, supporting further clinical development.