Rare Vision-Loss Gene Therapy Succeeds in Clinical Trial, Reversing Setback in Disease Targeted by Big Pharma

A treatment for a rare vision-loss disease demonstrated vision-improvement benefits in a pivotal clinical trial and is moving toward a U.S. Food and Drug Administration (FDA) approval application.

According to Fierce Biotech on the 21st (local time), Beacon Therapeutics met the primary endpoint in a Phase 2/3 trial of its gene therapy for X-linked retinitis pigmentosa (XLRP), laruparetigene zovaparvovec (laru-zova).

The Vista study tested two doses of laru-zova in 85 men, the primary patient population affected by XLRP. Patients were defined as responders if they could read at least 15 additional letters on an eye chart in low-light conditions 12 months after treatment.

No patients in the control group met the response criteria. By contrast, 24.1% of patients in the low-dose group and 31% in the high-dose group were identified as responders.

Beacon CEO Lance Valdo told Fierce Biotech in an interview, “The pivotal study demonstrated the potential therapeutic effect of this drug in a blinding disease that affects hundreds of thousands of patients worldwide.”

Beacon plans to initiate and complete a rolling biologics license application (BLA) with the FDA this year. It also plans to pursue approvals in the European Union (EU) and the United Kingdom, while remaining open to potential collaboration with partners that have market infrastructure and expertise.

CEO Valdo attributed laru-zova’s success to the trial design and the drug itself. Biogen previously failed in a trial in 2021 that used retinal sensitivity as the primary endpoint, while Johnson & Johnson (J&J) also suffered a major setback last year in a Phase 3 trial evaluating the ability to navigate a virtual maze.

He said, “Sometimes it can be advantageous to be the second or third to try,” adding, “We were able to learn and improve thanks to the companies that came before us and the patients and clinicians who donated their time.”

Laru-zova delivers a full-length copy of the retinitis pigmentosa GTPase regulator (RPGR) gene in a viral capsid, which is injected directly into the back of the eye. The RPGR gene is inherently highly unstable, so Beacon optimized the genetic code to improve stability without altering the protein structure.

“Our secret is using codon optimization to create a stable, full-length gene that expresses the full-length protein,” CEO Valdo explained. “That protein takes its place in the photoreceptors and restores their function.”

RPGR mutations are one of the most common causes of XLRP. The disease causes the gradual loss of rod and cone cells in the retina, leading to vision loss, and symptoms may begin during the teenage years.

CEO Valdo said that when he took office in 2024, an acquaintance who was a retinal specialist told him, “I hate that disease. There is nothing I can do for the patients.” He added, “We have demonstrated that we can not only stop disease progression but also restore vision for patients.”