Laru-zova meets primary endpoint in pivotal VISTA trial for X-linked retinitis pigmentosa

Beacon Therapeutics announced its pivotal VISTA trial of laruparetigene zovaparvovec (laru-zova) met its primary endpoint. The subretinal gene therapy delivers a full-length copy of the RPGR^ORF15 gene. It produced meaningful gains in low luminance visual acuity (LLVA) at both dose levels tested, and a rolling Biologics License Application (BLA) is planned for later this year.¹

What VISTA showed

VISTA (NCT04850118) is a randomized, controlled phase 2/3 study that evaluated 85 male participants aged 12 to 48 years with RPGR-associated XLRP.¹ Participants received a high dose (6.8 E+11 vg/eye) or a low dose (3.7 E+11 vg/eye) of laru-zova or were assigned to an untreated control group. All were followed for 12 months.¹

The primary endpoint was the proportion of participants achieving a 15-letter or greater improvement in LLVA at month 12 compared with the untreated control group.¹ In the high-dose group, 31.0% met that threshold (p=0.0019), as did 24.1% of the low-dose group (p=0.0106). No participants in the control group reached this rate of improvement.¹ At the more sensitive threshold of 10 letters or more, responder 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 control group.¹

In microperimetry, the least-squares mean difference in mean macular sensitivity versus control was 1.201 dB in the high-dose group (p=0.0614) and 1.312 dB in the low-dose group (p=0.0405).¹

Safety and tolerability

Beacon described a favorable safety profile. Ocular treatment-emergent adverse events (TEAEs) were predominantly mild to moderate, balanced across groups, and largely attributed to the surgical procedure.¹ Laru-zova-related TEAEs were reported in 25% of the high-dose group and 38% of the low-dose group. Two ocular serious adverse events, both attributed to the procedure, occurred in the low-dose group.¹

Why the endpoint matters

The result lands in a field that has had a difficult few years. In May 2025, Ophthalmology Times reported that Johnson & Johnson’s phase 3 LUMEOS trial of botaretigene sparoparvovec, another RPGR gene therapy, did not meet its primary endpoint of improving vision-guided mobility. The company noted improvement on a majority of secondary endpoints.³ Cross-trial comparisons carry obvious limits, but the divergence underscores how heavily endpoint selection has shaped the XLRP pipeline. Beacon anchored VISTA on LLVA, a measure of function in dim conditions.

“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, who will present the data at AAO.¹ Lance Baldo, MD, Beacon’s CEO, characterized the results as “both statistically significant and clinically meaningful.”¹

The dose-response pattern will also draw attention. The high dose produced the larger proportion of 15-letter responders, whereas the low dose showed the higher proportion at 10 letters, and microperimetry differences were similar between the 2.

Building on earlier Beacon data

VISTA follows a series of earlier studies that supported the program. Ophthalmology Times reported in February 2024 that in the phase 2 SKYLINE trial, 63% of patients in the high-dose cohort met the microperimetry-based response definition at 12 months, while the low-dose cohort showed no response.⁴ In May 2026, 12-month data from the phase 2 DAWN trial presented at ARVO showed sustained visual function improvements, with VISTA already fully enrolled.⁵ Beacon says its clinical experience now spans 110 treated participants across VISTA, HORIZON, SKYLINE, and DAWN, drawing on a 5-year dataset.¹

Laru-zova has also accumulated regulatory support, including FDA Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations, EMA PRIME status, MHRA ILAP designation, and orphan drug designation from the FDA and EMA.^1,6 The RMAT designation, announced in early 2025, was based on preliminary phase 2 data from DAWN and SKYLINE.⁶

What comes next

Beacon plans to engage global regulators and begin a rolling BLA submission later in 2026.¹ If accepted, laru-zova would enter a retinal gene therapy landscape that is already shifting. The FDA recently accepted a BLA for Nanoscope’s mutation-agnostic optogenetic therapy MOGENRY (sonpiretigene isteparvovec) in retinitis pigmentosa with severe vision loss.⁷ Together, the 2 programs illustrate how quickly approaches to inherited retinal disease are moving toward regulatory decision-making.

References

1. Beacon Therapeutics reports positive topline data from the pivotal VISTA trial of laru-zova for the treatment of X-linked retinitis pigmentosa (XLRP). News release. GlobeNewswire. September 21, 2026. Accessed September 21, 2026. https://www.globenewswire.com/news-release/2026/09/21/3365349/30580/en/beacon-therapeutics-reports-positive-topline-data-from-the-pivotal-vista-trial-of-laru-zova-for-the-treatment-of-x-linked-retinitis-pigmentosa-xlrp.html

2. Harp MD. Beacon Therapeutics completes enrollment in phase 2/3 VISTA trial. Ophthalmology Times. July 8, 2025. Accessed September 21, 2026. https://www.ophthalmologytimes.com/view/beacon-therapeutics-completes-enrollment-in-phase-2-3-vista-trial

3. Filkins K. J&J gene therapy treatment fails primary endpoints. Ophthalmology Times. May 5, 2025. Accessed September 21, 2026. https://www.ophthalmologytimes.com/view/j-j-gene-therapy-treatment-fails-primary-endpoints

4. Hutton D. Beacon Therapeutics releases 12-month data from phase 2 SKYLINE trial of AGTC-501 for patients with X-linked retinitis pigmentosa. Ophthalmology Times. February 8, 2024. Accessed September 21, 2026. https://www.ophthalmologytimes.com/view/beacon-therapeutics-releases-12-month-data-from-phase-2-skyline-trial-of-agtc-501-for-patients-with-x-linked-retinitis-pigmentosa

5. Hoffman M. Laru-zova sustains visual function improvements at 12 months in XLRP gene therapy trial. Ophthalmology Times. May 7, 2026. Accessed September 21, 2026. https://www.ophthalmologytimes.com/view/laru-zova-visual-function-improvements-xlrp-gene-therapy

6. Harp MD. Beacon Therapeutics receives Regenerative Medicine Advanced Therapy designation for laruparetigene zovaparvovec (laru-zova). Ophthalmology Times. February 2, 2025. Accessed September 21, 2026. https://www.ophthalmologytimes.com/view/beacon-therapeutics-receives-regenerative-medicine-advanced-therapy-designation-for-laruparetigene-zovaparvovec-laru-zova-

7. Filkins K. FDA accepts BLA for MCO-010 in retinitis pigmentosa. Ophthalmology Times. September 9, 2026. Accessed September 21, 2026. https://www.ophthalmologytimes.com/view/fda-accepts-bla-for-mogenry-in-retinitis-pigmentosa