A Phase 1 trial investigating NGGT Biotechnology's novel gene therapy NGGT001 (rAAV2-hCYP4V2) has yielded promising safety results in patients with Bietti's crystalline dystrophy (BCD), a rare inherited retinal disease currently without available treatments.
The investigator-initiated trial, conducted across two sites in China, enrolled 12 patients who received subretinal injections of NGGT001 at two dose levels: 1.5x1011 and 3.0x1011 total vector genomes. After 12 months of follow-up, researchers reported no dose-limiting toxicities or severe adverse events related to the treatment.
Safety and Efficacy Findings
The safety profile proved particularly encouraging, with only one patient experiencing mild intraocular inflammation that resolved quickly. Minor procedure-related adverse events, including eyelid and subconjunctival edema, were mild and self-resolving.
On the efficacy front, treated eyes showed a mean improvement in best-corrected visual acuity (BCVA) letter score of 13.9 (SD, 13.1) at 12 months post-treatment, compared to 6.3 (7.4) in untreated fellow eyes. The median BCVA in treated eyes improved from 34 (20/200 Snellen) at baseline to 53 (approximately 20/80 Snellen) at 12 months.
Mechanism of Action and Treatment Approach
NGGT001 employs an adeno-associated virus (AAV) vector to deliver a functional copy of the CYP4V2 gene, aiming to restore enzymatic fatty acid metabolism in BCD patients. The gene therapy is administered through subretinal injection, targeting the underlying genetic cause of the disease.
"We are thrilled to see the results from our dose-escalation trial, which indicate the promise of NGGT001 to serve as a safe treatment for BCD," stated Yiting Liu, PhD, vice president of translational research at NGGT. "We look forward to further clinical trials to validate NGGT001's ability to provide a durable treatment for this debilitating inherited disease."
Study Context and Implications
Dr. Xiuju Chen of the Xiamen Eye Center of Xiamen University and colleagues noted that while visual improvements were observed, the magnitude fell within typical test-retest values for eyes with very low visual acuity. They suggested that improvements in both treated and untreated eyes might partially reflect a learning effect, with greater improvement in treated eyes possibly related to their worse baseline condition.
The study population comprised seven men and five women, with a mean age of 40.5 years (SD, 7.1). Notably, researchers observed sustained visual gains over the 12-month follow-up period in patients with residual autofluorescence in the fovea, indicating remaining functional photoreceptors.
These findings represent a significant step forward in addressing BCD, a condition characterized by mutations in the CYP4V2 gene affecting the retinal pigment epithelium. The results support further investigation of NGGT001 as a potential first-in-class treatment for this currently untreatable condition.
