Beacon’s XLRP gene therapy meets pivotal U.S. endpoint

Why it matters: X-linked retinitis pigmentosa (XLRP) mainly affects boys and men, and most cases stem from mutations in the RPGR gene. The disease typically begins with night blindness in childhood, followed by progressive loss of peripheral vision and, later, central vision.

• There is no approved treatment for RPGR-associated XLRP. Laru-zova is designed as a one-time gene-replacement therapy that addresses the underlying genetic defect.
• Two earlier late-stage RPGR gene-therapy trials, Biogen’s XIRIUS in 2021 and Johnson & Johnson’s LUMEOS in 2025, missed their primary endpoints. Beacon calls VISTA the first pivotal XLRP trial to meet its primary endpoint.

Zoom in: The Phase 2/3 VISTA trial randomized 85 boys and men aged 12 to 48 to one of two laru-zova doses, given in one study eye, or to an untreated control group.

Laru-zova is delivered beneath the retina to supply photoreceptors with a functioning copy of RPGR. Eligibility also requires genetic confirmation of an eligible RPGR variant; in a Janssen-funded study across nine European countries and Israel, the 150 patients with dated records received genetic confirmation an average of 16.4 years after their first symptoms.

• At 12 months, 31.0% of patients on the higher dose and 24.1% on the lower dose had gained at least 15 letters, or three lines, in low-luminance visual acuity (LLVA), an eye-chart test performed under dimmed conditions, against 0% of controls (p=0.0019 and p=0.0106).

The European question: Beacon’s EU CTIS filing and its VISTA design poster designate a different primary efficacy measure for Europe: change in mean retinal sensitivity across the whole test grid at Month 12, measured by microperimetry, which maps the faintest light a patient can detect at different points on the retina.

• Treated eyes gained 1.201 decibels more than controls at the higher dose (p=0.0614) and 1.312 decibels more at the lower dose (p=0.0405).
• Monday’s release instead groups microperimetry among “other secondary endpoints” and does not say whether the European primary efficacy objective was formally met.

Reality check: Patients undergo a vitrectomy, which removes the gel inside the eye, before laru-zova is delivered beneath the retina, and receive a peri-operative corticosteroid regimen.

• Adverse events related to laru-zova were reported in 25% of high-dose and 38% of low-dose patients.
• The low-dose group had two serious ocular adverse events, both attributed by Beacon to the surgical procedure.

Backstory: London-based investor Syncona launched Beacon in 2023 after acquiring U.S. developer AGTC and its XLRP programme. Beacon says each earlier trial helped resolve a different part of the development programme::

• HORIZON, with 29 patients, identified 6.8×10¹¹ vector genomes per eye as the maximum tolerated dose. The 14-patient randomized SKYLINE study reinforced that dose as the one to take forward.
• DAWN treated the other eye of 15 people who had previously received a full-length RPGR gene therapy and informed Beacon’s choice of LLVA response as the U.S. pivotal endpoint.

What’s next: Monday’s release gives no timeline for a European filing; Beacon says it will begin pre-submission discussions with regulators worldwide. It plans to start a rolling U.S. biologics license application later this year and will present more VISTA data at the American Academy of Ophthalmology meeting on Oct. 10.

• MeiraGTx is also preparing regulatory filings for bota-vec, the RPGR gene therapy tested in LUMEOS, after agreeing in April to reacquire the programme from J&J. It said in August that it expected filings in the U.S., Europe and Japan this year.

Bottom line: The open questions are whether the benefit lasts, which dose Beacon takes forward and how European regulators read a primary efficacy measure that produced different statistical results at the two doses.