Beacon Therapeutics' laru-zova hits primary endpoint in pivotal VISTA trial in XLRP
核心洞察
Beacon Therapeutics (搜索) reported positive topline results from the pivotal Phase 2/3 VISTA trial of laru-zova in X-linked retinitis pigmentosa (搜索), meeting its FDA-endorsed primary endpoint.
At Month 12, 31.0% of high-dose participants and 24.1% of low-dose participants gained at least 15 letters in low luminance visual acuity, versus no responders in the untreated control group.
VISTA is the first pivotal trial in XLRP to achieve its primary endpoint, and Beacon plans a rolling Biologics License Application submission later this year.
Beacon Therapeutics (搜索) reported positive topline results from the registration-enabling VISTA trial of laruparetigene zovaparvovec (laru-zova) in patients with X-linked retinitis pigmentosa (搜索) (XLRP), with the pivotal Phase 2/3 study meeting its FDA-endorsed primary endpoint at Month 12. VISTA is the first and only pivotal trial in XLRP to achieve its primary endpoint, according to the company.
The randomized, controlled trial evaluated 85 male participants aged 12 to 48 with XLRP caused by mutations in the retinitis pigmentosa (搜索) GTPase regulator (RPGR (搜索)) gene. Participants were assigned to a high dose of 6.8 E+11 vg/eye, a low dose of 3.7 E+11 vg/eye, or an untreated control group, and were followed for 12 months.
Low luminance visual acuity responder rates
The primary endpoint was the proportion of participants achieving an improvement of at least 15 letters in low luminance visual acuity (LLVA) at Month 12 compared with the untreated control group. Responder rates were 31.0% in the high dose group (p=0.0019) and 24.1% in the low dose group (p=0.0106), with no responders in the untreated control group.
"These results represent a landmark moment for the hundreds of thousands of patients worldwide living with XLRP who currently have no treatment options and no way to slow the loss of their sight," said Lance Baldo, MD, Chief Executive Officer of Beacon Therapeutics (搜索). "Today's data are both statistically significant and clinically meaningful, representing an important milestone for ocular gene therapy and demonstrating the potential for a one-time treatment to change the course of an inherited retinal disease."
Secondary endpoint trends
Secondary endpoints showed supportive positive trends across measures of visual function. For change from baseline in mean macular sensitivity measured by microperimetry (MP) across the whole grid at Month 12, the least-squares mean difference versus untreated control was 1.201 decibels (dB) in the high dose group (p=0.0614) and 1.312 dB in the low dose group (p=0.0405).
For the proportion of participants achieving at least a 10-letter improvement in LLVA at Month 12, rates were 48.3% in the high dose group (p=0.0002), 58.6% in the low dose group (p<0.0001), and 3.7% in the untreated control group.
"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," said Robert Sisk, MD, FACS, FASRS, of the Cincinnati Eye Institute and Professor of Ophthalmology at the University of Cincinnati. "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."
Safety profile
Laru-zova demonstrated a favorable safety and tolerability profile consistent with prior studies. Treatment emergent adverse events were predominantly mild to moderate and ocular, balanced across treatment groups, and largely attributed to the surgical procedure. Laru-zova-related treatment emergent adverse events were reported in 25% of participants in the high dose group and 38% in the low dose group. Two ocular serious adverse events occurred in the low dose group, both attributed to the surgical procedure.
The results expand the evidence base for laru-zova, which now includes five years of clinical experience across 110 treated participants, spanning the prior HORIZON, SKYLINE, and DAWN trials. HORIZON (NCT03316560) was a completed five-year Phase 1/2 open-label dose escalation trial in 29 male participants who received a single subretinal dose in one eye. SKYLINE (NCT06333249) is a fully enrolled Phase 2 randomized, controlled trial in 14 male patients, with a primary endpoint of microperimetry response between the study and fellow eye at Month 12. DAWN (NCT06275620) is a fully enrolled Phase 2 open-label trial in the fellow eye of previously treated participants and is the first trial in the program to collect LLVA data.
Regulatory path and disease context
Based on the topline results, Beacon plans to engage with global regulatory authorities and intends to initiate a rolling Biologics License Application submission later this year. Additional VISTA data will be presented in a late-breaking oral presentation at Retina Subspecialty Day during the AAO Annual Meeting in New Orleans, Louisiana, on October 10, 2026, by Robert Sisk.
Laru-zova is designed to restore the natural function of both rods and cones in XLRP by delivering a functional copy of the full RPGRORF15 gene intended to produce the full-length protein. It holds Regenerative Medicine Advanced Therapy and Fast Track designations from the FDA, Priority Medicines (PRIME) designation from the European Medicines Agency (搜索), Innovative Licensing and Access Pathway designation from the UK's Medicines and Healthcare products Regulatory Agency (搜索), and Orphan Drug Designation from both the FDA and EMA. Laru-zova remains investigational and has not been approved by the FDA.
XLRP predominantly affects males and is typically caused by mutations in the RPGR (搜索) gene, which affect approximately 1 in 25,000 males in the U.S., Europe and Australia. The disease causes progressive photoreceptor loss and visual dysfunction beginning in childhood, eventually leading to blindness. It accounts for about 10% of the 100,000 retinitis pigmentosa (搜索) patients in the United States, and there are estimated to be more than 20,000 patients in the U.S. and Europe. No treatments are currently approved.
"For people living with XLRP, this is the news we have been waiting years to hear," said Jason Menzo, Chief Executive Officer of the Foundation Fighting Blindness. "XLRP is a relentlessly progressive disease with no approved treatments. This is the first pivotal study of a potential treatment for XLRP to achieve its primary endpoint with statistical significance."