Zhongyin Tech's Ophthalmic Gene Therapy ZVS101e Injection Nominated for CDE Priority Review

On August 7, the CDE website showed that CHIGENOVO’s ophthalmic gene therapy drug ZVS101e injection is proposed to be included in the priority review, forTreatmentCrystalline Retinal Dystrophy with Biallelic CYP4V2 Mutations (Bietti Crystalline Corneoretinal Dystrophy, BCD).

ZVS101e is a collaborative development by Peking University Third Hospital and CHIGENOVO.Gene augmentation therapy delivers functional copies of the CYP4V2 gene to patients with Bietti crystalline dystrophy (BCD) via recombinant adeno-associated virus.

In a randomized, controlled Phase III trial, patients received a single subretinal injection of ZVS101e (7.5×10¹⁰ vg/eye; n=31) at baseline or were assigned to an untreated control group (n=32). The primary endpoint was the proportion of subjects achieving an improvement in best-corrected visual acuity (BCVA) of at least 15 letters from baseline at Week 52. Secondary endpoints included changes from baseline in BCVA, Multi-Luminance Mobility Test (MLMT), Full-Field Stimulus Threshold (FST), and the Visual Function Questionnaire-25 (VFQ-25) at Week 52.

At Week 24, 10 out of 31 subjects (35%) in the treatment group achieved an improvement in BCVA of at least 15 letters from baseline, whereas only 1 out of 32 subjects (3%) in the control group met this criterion (p=0.001).

For the secondary endpoints, the mean improvement in BCVA was 11.5 letters in the treatment group and 1.5 letters in the control group, with a between-group difference of 10 letters (p<0.001). The mean change in MLMT score was 0.62 points in the treatment group and -0.44 points in the control group (p=0.017).

Under red light stimulation, the mean change in FST from baseline was −0.23 log cd·s/m² in the treatment group and 0.32 log cd·s/m² in the control group (p=0.038); more negative values indicate greater improvement in sensitivity. The mean changes in the VFQ-25 composite score were 3.35 points in the treatment group and −1.36 points in the control group (p=0.254).

No serious adverse events occurred in the treatment group; one subject in the control group experienced two serious adverse events.

Bietti Crystalline Dystrophy (BCD) is a distinct form of retinitis pigmentosa, characterized by the deposition of yellowish-white, glistening crystalline material in the retina. Clinical manifestations include night blindness, progressive vision loss, and visual field constriction. Patients typically become blind by around 40 years of age, and currently, there are no effective treatments available. There are approximately 60,000 to 140,000 BCD patients in China, making it one of the significant causes of irreversible bilateral blindness among the working-age population. BCD is caused by mutations in the CYP4V2 gene and follows an autosomal recessive inheritance pattern. These mutations result in the loss of function of the encoded protein, rendering the condition suitable for gene replacement therapy.

Currently, there are no approved targeted therapies for BCD worldwide, resulting in a significant unmet clinical need. With its outstanding innovativeness and breakthrough clinical value,ZVS101eSecured multiple prestigious domestic and international qualifications and certifications: In 2021, it received Orphan Drug Designation from the U.S. FDA; in 2024, it was granted Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. FDA, becoming the first ophthalmic gene therapy product in China to achieve this certification. Meanwhile, the pipeline also received Breakthrough Therapy Designation from China’s NMPA in 2024.ZVS101e Will Submit Marketing Authorization Application in the Second Half of the Year。