AAV Gene Therapy Shows Promise in Restoring Sight for Advanced Retinitis Pigmentosa

November 27, 2025-Zhongmou Therapeutics has announced promising initial results from a first-in-human trial of its AAV vector-based optogenetic gene therapy, ZM-02, offering a potential breakthrough for patients with advanced retinitis pigmentosa (RP). The single-dose therapy demonstrated both significant visual improvement and a favorable safety profile in the small, randomized MOON study (NCT06292650).

Key Findings from the MOON Study

The trial, which enrolled 12 patients at a single site in Beijing, China, and compared the drug against a sham control, revealed clinically meaningful gains in functional vision:

• Visual Acuity: As many as 83% of treated patients achieved a  ≥0.3 logarithm of the minimum angle of resolution (LogMAR) improvement in best-corrected visual acuity (BCVA) at 36 weeks.

• Magnitude of Gain: The mean gain in BCVA was $0.59$ LogMAR, which is equivalent to an improvement of approximately 30 early treatment diabetic retinopathy study (ETDRS) letters.

• Functional Vision: Patients reported significant improvements in multi-luminance mobility testing, which includes low-light navigation. Importantly, patients saw a recovery of real-world navigation ability and, for the first time in an optogenetic therapy, a restoration of colour vision.

• Durability and Safety: The company reported that the durability of the improvement has been sustained at the 52-week follow-up after just a single dose of ZM-02. Furthermore, the therapy showed a robust safety profile with no drug-related serious adverse events (SAEs) or dose-limiting toxicities (DLTs).

Zhongmou’s chief strategy officer, Dr. Zhenghong Gao, emphasized the broader impact of the data, stating: “The ZM-02 FIH data underscore how optogenetics is shifting the treatment landscape for patients with advanced retinal degeneration and generating meaningful clinical enthusiasm across the field.”

The Mechanism: Optogenetics and AAV Delivery

ZM-02 is an adeno-associated virus (AAV) vector-based gene therapy. It works using optogenetics, a mutation-agnostic approach that delivers a light-sensitive protein gene via injection into the eye. This light-sensitive protein is expressed in the remaining inner retinal cells, essentially turning them into new photoreceptors to bypass the degenerated cells.

Retinitis Pigmentosa: A High Unmet Need

RP comprises a cluster of uncommon eye conditions that cause progressive degeneration of the retina, ultimately leading to severe vision loss and blindness.

The current treatment landscape for RP remains limited. The only approved drug is Roche’s AAV gene therapy, Luxturna (voretigene neparvovec), which is only indicated for a specific, rare genetic mutation.

• Prevalence: A report by GlobalData predicts that the number of diagnosed prevalent cases of RP will reach 1,088,269 in 2029 across the 16 major pharmaceutical markets.

• Pipeline Activity: While the market is currently sparse, several other gene therapies are in the pipeline, including Ocugen’s OCU400 in a Phase III trial and Beacon Therapeutics’ laru-zova, which received a Regenerative Medicine Advanced Therapy (RMAT) designation from the US FDA in January 2025.

• Setbacks: The high-risk nature of the field was highlighted by Johnson and Johnson (J&J), whose acquired drug, botaretigene sparoparvovec, failed to meet its primary endpoint in a Phase III trial.

Despite the challenges, a number of drugs—as many as 34 candidates—are currently in trials for RP, with 22 of those in Phase II studies, showcasing the industry’s focus on this underserved patient population.