Beacon’s emerging XLRP gene therapy improves low-light vision in phase 3 trial

Beacon Therapeutics reported positive results from the Phase 3 pivotal trial of laru-zova, its potential gene therapy treatment for X-linked retinitis pigmentosa. A significant proportion of patients improved dim-light vision by 15 or more letters after treatment with either high or low doses of laru-zova compared to the group that was not treated, according to preliminary results from the VISTA clinical trial. Beacon plans to begin seeking FDA approval later this year. If approved, this would be the first treatment available for XLRP, one of the more severe forms of retinitis pigmentosa that predominantly affects males.

Laru-zova specifically targets mutations in the RPGR gene, the most common cause of XLRP. The treatment is given once, as an injection beneath the retina, and uses an adeno-associated virus to deliver working copies of the RPGR gene to retinal cells.

XLRP patients improved dim light vision by more than 10 letters

VISTA compared the effect of two different doses of laru-zova in 85 males ages 12 to 48 over the course of one year. The study’s primary measure was low-luminance visual acuity, or how well someone can read an eye chart in dim light. At 12 months, 31% of patients who received the high dose and 24% who received the lower dose gained at least 15 letters of dim-light vision. None of the untreated patients made these vision gains, a difference that was statistically significant for both doses. A larger number of participants had smaller vision gains of at least 10 letters across high dose (48%) and low dose (58%) groups, compared to 4% in the untreated group. A secondary measure of central retinal sensitivity also improved in the treated groups.

“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.”

Safety was consistent with earlier trials

Most side effects were mild or moderate and were largely attributed to the surgery used to deliver the therapy. Some were attributed to laru-zova itself, in 25% of patients in the higher-dose group and 38% of the lower-dose group. Two serious eye-related events, both in the lower-dose group, were tied to the procedure. Beacon said the safety profile has held across five years and 110 treated patients. The company reported vision improvements for patients receiving laru-zova in three earlier clinical trials: HORIZON, SKYLINE, and DAWN.

Beacon plans to file a rolling application with the FDA later this year and to share fuller VISTA data at the American Academy of Ophthalmology meeting in New Orleans on October 10.

The Foundation has a longstanding connection to Beacon’s XLRP therapy since funding the pre-clinical research that went on to became laru-zova. The Foundation’s venture philanthropy arm the Gund Vision Fund – formerly known as the RD Fund – also invested in Beacon earlier this year to help advance laru-zova towards approval.

Learn more about retinitis pigmentosa and the latest research advances.