Phase III Win: Laru-Zova Shows Meaningful Vision Gains for XLRP Patients

Beacon Therapeutics announced that its Phase III VISTA trial (NCT04850118) of laruparetigene zovaparvovec (laru-zova) met its primary and key secondary endpoints, marking a major advance for people with X-linked retinitis pigmentosa (XLRP).

VISTA Trial Results

In the randomized VISTA study, a statistically significant proportion of treated patients achieved clinically meaningful improvements in low-luminance visual acuity (LLVA). Specifically, ≥15-letter LLVA gains were observed in 31% of participants in the high-dose cohort and 24.1% in the low-dose cohort, versus 0% in the untreated control arm. Improvements in mean macular sensitivity versus control (least-squares mean difference) were 1.201 dB for the high-dose arm and 1.312 dB for the low-dose arm.

At 12 months, a ≥10-letter LLVA gain was seen in 48.3% of high-dose subjects and 58.6% of low-dose subjects, compared with 3.7% in controls, indicating durable and clinically relevant benefits for many treated patients.

Clinical Perspective

"Beacon selected endpoints that would best capture improvements that matter to patients, particularly their ability to see in low-light conditions, which is one of the most challenging aspects of living with XLRP. Achieving high statistical significance in 15-letter or greater improvement in LLVA demonstrates a clinically meaningful and consistent treatment effect in VISTA, reinforcing confidence in laru-zova's potential to become a first-in-disease therapy," said Dr. Robert Sisk of the Cincinnati Eye Institute, a trial investigator and professor of ophthalmology at the University of Cincinnati.

Safety Profile

Laru-zova was generally well tolerated. Most treatment-emergent adverse events (TEAEs) were mild to moderate ocular events. Laru-zova–related TEAEs were reported in 25% of participants in the high-dose arm and 38% in the low-dose arm. Two ocular serious adverse events (SAEs) occurred in the low-dose group; both were attributed to the surgical procedure.

Regulatory Plans and Program Context

Beacon said VISTA is the first and only pivotal trial in XLRP to meet its primary endpoint. These results build on earlier positive data from the company's HORIZON, SKYLINE and DAWN (NCT06275620) studies, and laru-zova is additionally being evaluated in the LANDSCAPE trial (NCT07174726). Based on VISTA, Beacon plans to engage global regulators and initiate a rolling Biologics License Application (BLA) submission.

About Laru-Zova and XLRP

Laru-zova is a gene therapy designed to restore function in both rods and cones by delivering a functional copy of the RPGR ORF15 gene to produce the full-length RPGR protein. XLRP is a rare, progressive retinal disease that disproportionately affects low-light (scotopic) vision. There are currently no approved pharmaceutical treatments or gene therapies specifically for XLRP.

Market Outlook

A GlobalData analysis forecasts that cases of retinitis pigmentosa (RP) across the 16 major pharmaceutical markets (US, France, Germany, Italy, Spain, UK, Japan, Australia, Brazil, Canada, China, India, Mexico, Russia, South Africa and South Korea) will rise from about 1.04 million in 2024 to roughly 1.08 million by 2029, underscoring the continued unmet need.

Bottom line: The VISTA Phase III readout positions laru-zova as a promising first-in-disease candidate for XLRP, with clear functional benefits in low-light vision and an acceptable safety profile that supports regulatory engagement.