Development

Beacon's laru-zova becomes first XLRP gene therapy to meet pivotal trial primary endpoint

Beacon's laru-zova becomes first XLRP gene therapy to meet pivotal trial primary endpoint

Beacon Therapeutics' laruparetigene zovaparvovec met the primary endpoint in the pivotal VISTA trial in X-linked retinitis pigmentosa (XLRP), with both tested doses producing significantly higher rates of clinically meaningful low-luminance visual acuity improvement than untreated control. Beacon said it plans to begin a rolling BLA submission before year-end for the gene therapy, which is being developed for a disease with no approved treatments.

Laru-zova delivers a functional copy of the full-length RPGR ORF15 gene using an adeno-associated virus vector, with the aim of restoring function across both rod and cone photoreceptors affected by RPGR mutations. The VISTA primary endpoint measures low-luminance visual acuity, a functionally relevant measure in XLRP because patients typically experience early difficulty seeing in dim-light conditions before more advanced visual loss develops.

The result also distinguishes Beacon's program from MeiraGTx's botaretigene sparoparvovec, another RPGR-directed AAV gene therapy that failed to meet the primary endpoint in the Phase III LUMEOS trial in May 2025. MeiraGTx subsequently reacquired bota-vec from Johnson & Johnson in April 2026 and has said it still intends to pursue regulatory filings. LUMEOS used a navigation-based functional vision endpoint, while VISTA's FDA-endorsed primary endpoint focused on low-luminance visual acuity.

VISTA enrolled 85 male patients aged 12 to 48 with RPGR-associated XLRP and randomized them to high-dose laru-zova, low-dose laru-zova, or an untreated control. At Month 12, 31.0% of patients in the high-dose group and 24.1% in the low-dose group achieved at least a 15-letter improvement in low-luminance visual acuity, compared with no responders in the control group. At least a 10-letter improvement was achieved by 48.3% and 58.6% of patients in the two dose groups, respectively, versus 3.7% of controls.

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Microperimetry also showed improved macular sensitivity, reaching statistical significance in the low-dose group but narrowly missing significance at the high dose. Treatment-emergent adverse events were predominantly mild to moderate and largely related to the surgical procedure; two ocular serious adverse events occurred in the low-dose group, both attributed to the procedure.

Beacon holds FDA Regenerative Medicine Advanced Therapy (RMAT) designation for laru-zova, granted in January 2025. The VISTA data build on five years of clinical experience across 110 treated participants in the Phase I/II HORIZON, Phase II SKYLINE, and Phase II DAWN studies, with DAWN reporting sustained 12-month low-luminance visual acuity improvements at ARVO in May 2026. Full VISTA results are scheduled for presentation in a late-breaking oral session at the American Academy of Ophthalmology Annual Meeting on October 10, 2026.


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