NGGT-001: A Comprehensive Review of an Investigational Gene Therapy for Bietti's Crystalline Dystrophy

Abstract

NGGT-001 (rAAV-hCYP4V2) is an investigational adeno-associated virus serotype 2 (AAV2)-based gene therapy developed by Next Generation Gene Therapeutics (NGGT) Inc. for the treatment of Bietti's Crystalline Dystrophy (BCD). BCD is a rare, autosomal recessive retinopathy caused by mutations in the CYP4V2 gene, leading to dysfunctional fatty acid metabolism, lipid crystal accumulation in the retina and cornea, and progressive vision loss. NGGT-001 aims to deliver a functional, codon-optimized CYP4V2 gene via subretinal injection to restore enzymatic activity, primarily in the retinal pigment epithelium (RPE). An early-phase 1/2 open-label, dose-escalation clinical trial (NCT06302608) involving 12 patients in China evaluated two dose levels (1.5×1011 and 3.0×1011 vector genomes). At 12 months, NGGT-001 demonstrated a favorable safety profile, with no severe adverse events related to treatment and one instance of mild, resolved intraocular inflammation. Encouraging preliminary efficacy was observed, with a mean improvement in best-corrected visual acuity (BCVA) of 13.9 letters in treated eyes compared to 6.3 letters in untreated fellow eyes, though a learning effect was noted as a potential confounder. Sustained visual gains were particularly noted in patients with residual foveal autofluorescence. NGGT-001 has received Orphan Drug Designation from the U.S. FDA. Future development will require larger, controlled trials with longer follow-up and objective endpoints to confirm efficacy and long-term safety. NGGT Inc.'s in-house cGMP manufacturing capabilities and broader pipeline suggest a strategic approach to gene therapy development.

1. Introduction to NGGT-001 and Bietti's Crystalline Dystrophy (BCD)