A gene therapy that targets a form of retinitis pigmentosa showed a signal to improve retinal function for up to 3 years after treatment, according to a small clinical trial.

The phase 2 SKYLINE trial of the gene therapy lura-zova — short for laruparetigene zovaparvovec — “showed the high-dose treatment produced sustained improvement in retinal sensitivity through month 36,” Paul Yang, MD, PhD, chief of the genetics division at Oregon Health and Science University in Portland, Oregon, told attendees at the European Society of Retina Specialists (EURETINA) 2025 in Paris, France.

The trial enrolled 14 males aged between 8 and 50 years with X-linked retinitis pigmentosa, a degenerative disease caused by mutations in the RPGR gene. Eight patients were in the high-dose group, receiving 680 billion vector genes per eye; six were in the low-dose group, receiving a dose of 75 billion vector genes per eye. The vectors are surgically placed under the retina.

Increase in Retinal Sensitivity 

The measure of efficacy for the treatment was a more than 7-decibel improvement from baseline in more than five loci, or positions, in the chromosome. A decibel is a measure of retinal sensitivity to light; the higher the decibel, the greater the retina’s ability to detect lower light levels.

At 3 years, four of seven eyes in the high-dose group (57%) met that standard, whereas none of the fellow, untreated eyes in these patients did so. “Moreover, change from baseline in mean sensitivity in the study eye increased compared to a decrease in the fellow control eye as well as all the other eyes in the low-dose group,” Yang said.

Retinal sensitivity was measured using microperimetry. “Microperimetry is a measure of visual sensitivity to light, but it is not correlated with visual acuity,” Yang told Medscape Medical News.

Yang also explained the reasoning for the primary efficacy target. “This 7-decibel/five-loci criteria is somewhat controversial because Biogen’s phase 2/3 RPGR gene therapy program failed to meet this criteria, and specialists generally feel this is too high a bar,” he said. “Sponsors are a bit reluctant to use microperimetry again as a pivotal endpoint because of Food and Drug Administration insistence on the 7-decibel/five-loci rule.” Yang referred to the failed phase 2/3 XIRIUS trial of cotoretigene toliparvovec to treat X-linked retinitis pigmentosa.

Patients in the SKYLINE trial tolerated the treatment well and had an acceptable level of adverse events, he added. Those in the low-dose group experienced two ocular adverse events — one case each of glaucoma and visual impairment — and six treatment-related adverse events. Patients in the high-dose group experienced two cases of vitritis, which were treated with corticosteroids and resolved in 4 months, Yang said. No adverse events were reported in the fellow, untreated eyes.

The study results so far support using the high-dose treatment in phase 3 trials, Yang said. Follow-up of the SKYLINE trial is ongoing through 5 years, he added. 

Twelve-month data from the phase 2/3 VISTA trial of lura-zova are expected “in a year or so,” Yang said. The primary endpoint of VISTA is low-luminance visual acuity, a measure of dark-adapted cone function or reading in dim light. 

“These findings are encouraging for a gene augmentation strategy targeting one of the most prevalent forms of retinitis pigmentosa,” Neiraj Jain, MD, retina specialist at Emory University in Atlanta, said. “The long-term results suggest durable efficacy signal with tolerable safety profile, supporting further development of the product.”

The SKYLINE data did not include 36-month results for some eyes, he said, and other control eyes exited the study because they ultimately received treatment as part of a companion study. “It would be useful to see the last available functional data on these eyes,” Jain said.

“Additionally,” he said, “it is worth noting that this study did not assess low luminance visual acuity” — the primary endpoint for the ongoing pivotal phase 2/3 VISTA trial.

The study was funded by Beacon Therapeutics. Yang reported having financial relationships with Beacon Therapeutics, 4D Molecular Therapeutics, AAVantgarde Bio, Biogen, Endogena, Janssen/MeiraGTx, Nanoscope Therapeutics, Ocugen, and Spark Therapeutics. Jain reported serving as an investigator for Janssen/MeiraGTX.

Richard Mark Kirkner is a medical journalist based in Philadelphia.