Gene and Cell Therapy · uk
Progress reported in gene therapy for inherited retinal disease: VISTA trial improves low-light vision in some patients
Being able to read a few more lines in dim light may represent a meaningful change for people whose vision is gradually deteriorating. The pivotal trial of laru-zova met its primary efficacy endpoint, but how long the improvement lasts and how to weigh the surgical risks remain important questions on the path to approval.
For patients with X-linked retinitis pigmentosa (XLRP), dimming light often makes the world around them harder to discern; as the disease progresses, their peripheral visual field may also gradually narrow. Now, a gene therapy targeting RPGR gene mutations has improved some patients’ ability to identify letters in low-light conditions in a randomized controlled trial, providing new clinical evidence for this progressive inherited eye disease.
The NIHR Oxford Biomedical Research Centre at the University of Oxford described the findings on September 29; the developer, Beacon Therapeutics, had announced preliminary topline results from the VISTA trial on September 21. This pivotal Phase 2/3 trial enrolled 85 male patients aged 12 to 48 with RPGR mutations, assigned to high-dose, low-dose, and untreated control groups, to evaluate efficacy and safety over 12 months. *Retinal Physician* and *Ophthalmology Times* also reported the same results.
The trial’s primary endpoint was whether patients could identify at least 15 more letters on a low-luminance visual acuity test than before treatment. At 12 months, 31.0% of the high-dose group and 24.1% of the low-dose group reached this threshold, while no one in the untreated group did; comparisons between each treatment group and the control group were statistically significant, with p-values of 0.0019 and 0.0106, respectively. This means that some patients benefited on a specific vision test. It does not mean that everyone who received treatment regained vision, nor should the fact that no one in the control group reached the threshold be interpreted as a complete absence of any improvement.
The therapy, called laruparetigene zovaparvovec, or laru-zova for short, delivers a functional, full-length RPGR ORF15 gene into retinal cells through subretinal administration. The aim is to enable the cells to produce the protein they need to support the function of rod and cone photoreceptors. RPGR mutations damage these photoreceptors; the gene supplementation strategy seeks to address the functional defect, but these results are not yet sufficient to demonstrate that it can rebuild cells that have already been lost or prevent disease progression over the long term.
Other measures of visual function provided additional clues, while also showing that the effects were not equally clear across all measures. Microperimetry, which assesses the macula’s sensitivity to light, showed differences of 1.201 and 1.312 decibels for the high- and low-dose groups, respectively, compared with the untreated group, with p-values of 0.0614 and 0.0405. This comparison in the high-dose group did not meet the commonly used significance threshold of 0.05; more data are still needed to clarify the full analysis and how multiple comparisons were handled.
Safety must be assessed together with the surgery used to administer the therapy. According to data released by Beacon and relayed by the two ophthalmology publications, ocular adverse events were mostly mild to moderate; treatment-emergent adverse events judged to be related to laru-zova occurred in 25% and 38% of participants in the high- and low-dose groups, respectively. There were also two serious ocular adverse events in the low-dose group, both attributed to surgery. This attribution still means that patients undergoing the complete treatment must bear the risks of the procedure itself.
Beacon plans to begin a rolling submission of a Biologics License Application to the US FDA later in 2026 and to present more VISTA data at a meeting associated with the American Academy of Ophthalmology annual meeting on October 10. Laru-zova remains an investigational therapy; meeting the primary endpoint is an important step toward seeking approval, while the actual review must still assess the complete efficacy, safety, and other data. Its longer-term significance for patients will depend on whether the improvements persist and the extent to which gains on the tests translate into visual abilities in daily life.