Phase 2 SKYLINE Trial Shows Promising Results for Gene Therapy in X-Linked Retinitis Pigmentosa
核心洞察
The Phase 2 SKYLINE trial demonstrated significant improvement in microperimetry response with high-dose laru-zova gene therapy compared to low-dose treatment in males with X-linked retinitis pigmentosa (搜索).
Patients aged 8 to 50 with pathogenic RPGR (搜索) gene variants and intact foveal ellipsoid bands showed the greatest benefit from the full-length RPGR gene therapy (搜索).
The Phase 3 VISTA trial is already fully recruited and will evaluate both microperimetry and low luminance visual acuity as primary endpoints.
The Phase 2 SKYLINE trial has demonstrated significant visual improvements with high-dose laru-zova gene therapy in patients with X-linked retinitis pigmentosa (搜索) (XLRP (搜索)), according to 24-month results presented at the 2025 American Society of Retina Specialists (搜索) annual meeting in Long Beach, California.
Robert A. Sisk, MD, FACS, FASRS, from Cincinnati Eye Institute (搜索), reported that the randomized, controlled, multicenter trial showed a significant improvement in microperimetry response in the high-dose group compared to the low-dose group. Microperimetry measures visual sensitivity in the central retina, the portion treated with the gene therapy.
Trial Design and Patient Population
The SKYLINE trial evaluated the dose-dependent response of laru-zova, a full-length RPGR gene therapy (搜索), building on promising results from groups 2 and 5 in the previous Phase 1/2 HORIZON study. The trial enrolled males aged 8 to 50 years with demonstrated pathogenic variants in the RPGR (搜索) gene, which is the most common gene causing X-linked retinitis pigmentosa (搜索).
Strict inclusion criteria required participants to have measurable microperimetry sensitivity and an intact foveal ellipsoid band. The ellipsoid band serves as an anatomic marker indicating the integrity and health of photoreceptors in the retinal area that provides optimal vision.
Key Findings and Treatment Window
The trial results revealed that patients with measurable microperimetry and intact ellipsoid bands were more likely to benefit from gene therapy, consistent with findings from other gene therapy trials. "It seems like the ellipsoid zone is important. Having near-normal retinal anatomy in that area is important to see the benefit of the gene therapy," Sisk explained.
The research identified a narrow therapeutic window for optimal treatment outcomes. Patients must have some vision decline, specifically between 20/32 to 20/200 visual acuity, to demonstrate potential improvement while avoiding ceiling effects. However, as visual acuity declines further, there is typically loss of the ellipsoid band, making patients ineligible for treatment.
Phase 3 Development and Future Outlook
The Phase 3 VISTA trial is already fully recruited, incorporating lessons learned from SKYLINE. The trial will evaluate two primary endpoints: microperimetry, validated by the SKYLINE results, and low luminance visual acuity, established through the parallel DAWN trial.
Sisk expressed optimism about expanding treatment options if the Phase 3 study leads to approval. "I'm hopeful that if this gets approved, following the phase 3 study, that we'll be able to treat patients at an earlier age who may be able to benefit rather than having such a narrow recruiting window," he noted.
Comprehensive Treatment Strategies
Looking toward the future, researchers anticipate developing diverse therapeutic approaches for X-linked retinitis pigmentosa (搜索), including gene augmentation therapy, gene-agnostic approaches, stem cell studies, and optogenetic gene therapy for late-stage disease. The ultimate goal is to create comprehensive treatment strategies that combine various therapeutic methods to provide more complete outcomes for patients with this genetic condition.