NGGT Biotechnology’s Gene Therapy NGGT001 Continues to Show Encouraging Safety in Bietti’s Crystalline Dystrophy
At 12 months of follow-up, there were no dose-limiting toxicities and no severe adverse events related to the treatment reported.
Next Generation Gene Therapeutics (NGGT) Biotechnology’s NGGT001 (also known as rAAV2-hCYP4V2), an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Bietti’s crystalline dystrophy (BCD), did not show any substantial safety concerns in updated data from an early phase 1 investigator-initiated trial (NCT06302608).1
The trial, which treated 12 patients across 2 trial sites in China, utilized 2 dose levels: 1.5x1011 and 3.0x1011 total vector genomes of NGGT001. Six patients were treated at the lower dose, and 6 were treated at the higher dose.2
At 12 months of follow-up, there were no dose-limiting toxicities and no severe adverse events (AEs) related to the treatment reported.1 A mild case of intraocular inflammation occurred in 1 patient, but speedily resolved.
With regard to efficacy, a mean improvement in treated eyes of best-corrected visual acuity (BCVA) letter score of 13.9 (SD, 13.1) was recorded at 12 months posttreatment, whereas fellow eyes showed a mean improvement of 6.3 (7.4).2 At baseline, the treated eyes had a median BCVA letter score of 34 (IQR, 10-53; 20/200 Snellen) and the fellow eyes had a median BCVA of 60 (40-67; 20/63 Snellen). Furthermore, treated eyes showed a median BCVA of 53 (IQR, 37-64; approximately 20/80 Snellen) at 12 months posttreatment and fellow eyes showed a median BCVA of 62 (42-70; approximately 20/50 Snellen) at the same time point. NGGT Biotechnology noted that sustained visual gains were observed over the 12 months posttreatment follow-up period in patients with residual autofluorescence in the fovea, which the company pointed out is a sign of remaining functional photoreceptors.1
“This open-label, exploratory nonrandomized clinical trial identified no serious safety concerns related to gene therapy over 12 months’ follow-up among patients with BCD,” Xiuju Chen, MD, of the Xiamen Eye Center of Xiamen University, in Fujian, China, and colleagues concluded in the abstract of a report of the results published in JAMA Ophthalmology.2 “While improvement in BCVA was noted, the magnitude was within test-retest values typically noted in eyes with very low levels of visual acuity, and BCVA improvement in both the study and nonstudy eyes could be related to a learning effect, with greater improvement in the study eye possibly related to study eyes’ being the worse-seeing eye.”
The 12 patients in the trial had a mean age of 40.5 years (SD, 7.1). The group included 5 women and 7 men.
NGGT001 is intended to deliver a functional copy of the disease-targeted gene, CYP4V2, in order to restore enzymatic fatty acid metabolism in patients with BCD.1 The gene therapy is administered subretinally.
"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," Yiting Liu, PhD, the vice president of translational research at NGGT, said in a statement.1 "Across the 12-month span of patient follow-up, we observed promising indications of visual improvement following treatment with NGGT001 and no severe AEs. We look forward to further clinical trials to validate NGGT001's ability to provide a durable treatment for this debilitating inherited disease."
These results build on earlier findings from the trial that were previously reported in a poster by Chen and colleagues at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD.3 At the time, 11 patients, who had been followed for 9 months, were evaluable. Chen and colleagues noted in the poster that AEs related to the subretinal injection procedure used to administer NGGT001 included eyelid and subconjuctival edema, but that these AEs were mild in severity and resolved on their own.
“BCD is caused by mutations in the cytochrome P450 (CYP) family 4 subfamily V member 2 gene (CYP4V2) encoding a polyunsaturated fatty acid hydroxylase which is dominantly expressed in retinal pigment epithelium cells in the retina,” Chen and colleagues wrote in the poster’s abstract.3 “There has not been any treatment available for BCD. NGGT Biotechnology has developed NGGT001, an rAAV2-based vector expressing codonoptimized human CYP4V2 for treating BCD.”
