Gene therapy improves low-light vision in patients with rare retinal condition

A Phase 2/3 trial assessing a gene therapy for X-linked retinitis pigmentosa (XLRP) shows significant improvements in low-light vision.

The Phase 2/3 VISTA clinical trial evaluated the safety, tolerability and efficacy of a one-time gene therapy treatment for X-linked retinitis pigmentosa (XLRP). The study met its main goal, significantly improving patients' vision in low-light conditions. XLRP is a rare inherited condition, affecting predominantly males, that causes light-detecting cells in the retina to decay over time leading to severe sight loss. Night blindness is an early symptom often beginning in childhood, progressing to loss of peripheral vision and legal blindness by a median age of 45.

'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. Seeing positive study results in endpoints that measure the aspects of vision that matter most in everyday life provides hope for patients and families around the world.'

The VISTA trial, run by Beacon Therapeutics, enrolled 85 males aged between 12 and 48 years. Participants were assigned to one of three treatment groups: a higher-dose group, a lower-dose group or an untreated control group. The gene therapy, called laru-zova (laruparetigene zovaparvovec), delivers a functional copy of the RPGR gene to retinal cells. Mutations in this gene cause around 70 percent of XLRP cases.

After 12 months, 31 percent of patients who received the high-dose and 24.1 percent of patients who received the low-dose could read at least 15 letters more in a low-luminance visual acuity test (a standard measurement of vision in low-light conditions). In contrast, no patients in the untreated control group reached this level of improvement. Laru-zova also showed improvements in other measures of visual function. Microperimetry, which measures retinal sensitivity, showed increased mean macular sensitivity compared with the untreated group, although the difference was statistically significant only in the low-dose group.

Overall the therapy was well tolerated, with most eye-related adverse events reported as mild to moderate and seen across treatment groups. These events have been linked to the surgical procedure used to administer the therapy directly into the back of the eye. Two serious adverse events occurred in the low-dose group, though both were attributed to the surgical administration rather than the gene therapy itself.

'We now look forward to working closely with regulatory authorities to bring laru-zova to patients as quickly as possible,' said Dr Lance Baldo, chief executive officer of Beacon Therapeutics.

Beacon Therapeutics plans to submit a Biologics Licence Application to the US Food and Drug Administration on a rolling basis, filing data as it is available. While the VISTA trial results have not yet been published in a peer-reviewed journal, additional data will be presented at the upcoming American Academy of Ophthalmology meeting in New Orleans.