AZR-902 is an adeno-associated virus (AAV) serotype-based gene therapy designed to deliver a functional copy of the RPE65 gene via subretinal injection. This Phase III, randomized, double-masked, sham-controlled trial evaluated the efficacy and safety of a single intravitreal/subretinal dose of AZR-902 (2.0 × 10¹¹ vg) in subjects aged 12–65 with confirmed biallelic RPE65 mutations and severe visual impairment.
The study enrolled 78 subjects across 34 clinical sites in North America and Europe. Participants were randomized 1:1 to receive either AZR-902 or a matched sham procedure. Masking was maintained for all investigators, assessors, and participants until database lock.
Baseline characteristics were balanced between arms. The treatment cohort showed a mean improvement of 24.3 ETDRS letters at Month 12 compared to 2.1 letters in the sham group.
| Endpoint | AZR-902 (N=39) | Sham Control (N=39) | Least Squares Mean Diff | p-value |
|---|---|---|---|---|
| Δ BCVA (Month 12) | +24.3 ± 9.4 | +2.1 ± 5.2 | +22.2 | < 0.001 |
| Δ FST Sensitivity (Month 12) | +18.7 ± 7.1 dB | +1.4 ± 4.3 dB | +17.3 dB | < 0.001 |
| Δ Outer Retinal Thickness (OCT) | +2.8 ± 1.1 μm | -0.4 ± 0.9 μm | +3.2 μm | 0.003 |
| % Responders (≥15 letter gain) | 76.9% | 7.7% | 69.2% | < 0.001 |
| NEI-VFQ-25 Composite Δ | +14.2 ± 6.8 | +1.9 ± 5.1 | +12.3 | 0.002 |
All efficacy signals remained stable through Month 18 in the treatment arm, with no evidence of immune-mediated vector clearance or photoreceptor degeneration post-intervention.
Overall treatment-related adverse events (TRAEs) were mild to moderate. No subjects discontinued due to adverse events. Immune monitoring showed transient, low-titer anti-AAV antibodies in 12.8% of treated participants, none of which correlated with clinical outcomes or required immunosuppression.
| Adverse Event Category | AZR-902 (N=39) | Sham (N=39) | Grade 3+ / SAEs |
|---|---|---|---|
| Any TRAE | 24 (61.5%) | 8 (20.5%) | 0 |
| Conjunctival injection / Iritis | 18 (46.2%) | 6 (15.4%) | 0 |
| Elevated IOP (transient) | 7 (17.9%) | 1 (2.6%) | 0 |
| Headache / Nausea | 9 (23.1%) | 5 (12.8%) | 0 |
| Serious Adverse Events | 2 (5.1%) | 3 (7.7%) | Unrelated |
The AZ-GT01 trial demonstrates that a single dose of AZR-902 provides statistically and clinically significant restoration of visual function in RPE65-associated retinal dystrophy. The durability of response through 18 months, combined with a favorable safety profile, supports regulatory filing for accelerated and priority review pathways.
Zenth Health Sciences has initiated preparation of a Biologics License Application (BLA) with the FDA and a Marketing Authorization Application (MAA) with EMA. An open-label extension study (NCT06124489) is ongoing to assess long-term outcomes beyond 36 months.