Gene Therapy Improves Functional Measures in XLRP


Investigators found AGTC-501 to have a favorable benefit-risk profile.

Patients with X-linked retinitis pigmentosa (XLRP) treated with AGTC-501 gene therapy experienced improvements in visual function including retinal sensitivity as assessed by macular Integrity Assessment (MAIA) microperimetry and full-field stimulus threshold (FST) with a favorable benefit-risk profile.1

Updated, 12-month data from the phase 2 SKYLINE trial (NCT04850118) were presented by Mark Pennesi MD, PhD, Director, Ophthalmic Genetics Retina Foundation Dallas, and Texas Professor of Ophthalmology Professor of Molecular and Medical Genetics, Paul H. Casey Ophthalmic Genetics Division Casey Eye Institute, Oregon Health & Science University, at the 47th Annual Maula Society Meeting, held Feb 07 - 10, 2024, in Palm Springs, California.1

“The benefit-risk profile is favorable and supports continued clinical development for the treatment of patients with XLRP caused by RPGR mutations,” Pennesi said during his presentation.

AGTC-501 delivers a full-length RPGR via an adeno-associated virus (AAV) vector delivered by subretinal injection.

The data are from 14 participants, 6 that received low-dose (7.5 E+10 vg/eye) and 8 that received high-dose (6.8 E+11 vg/eye) AGTC-501.

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"These data, which demonstrate a favorable safety profile and notable improvement in visual function, are another positive step in the development of AGTC-501 for XLRP, a blinding, orphan disease for which there is currently no approved treatment. We look forward to announcing the initiation of our Phase 2/3 VISTA trial in the first half of 2024,” Nadia Waheed, PhD, Chief Medical Officer, Beacon Therapeutics, said in a statement.2

Investigators found that there were no ocular serious adverse events (AERs) deemed related to AGTC-501. There was 1 case of severe glaucoma found related to protocol required corticosteroids which was treated with medication and resolved by Study Day 181 and 1 case of visual impairment found related to injection procedure which is ongoing. Treatment-related AEs included vitritis, eye pain, metamorphopsia, photopsia, and reduced visual acuity (all n = 1). Ocular treatment-emergent (AEs) were mostly non-serious, mild or moderate in severity, and rates were similar between high dose and low dose groups. All related treatment-emergent AEs to AGTC-501 were considered mild or moderate in severity and those related to the injection procedure were considered mild or moderate in severity.

Seventeen percent of patients in the low-dose cohort and 63% of the high-dose cohort achieved at least a 7 dB improvement from baseline in at least loci at month 12. Patients in the high dose cohort also had improvements in baseline mean sensitivity in MAIA. These patients also showed statistically significant improvements in their treated eyes on Red and White light FST compared to both the low dose and the untreated control eyes, with a strong trend in blue light FST.

Similar results were seen with multi-luminance mobility maze test, with 9 of 14 treated eyes showing at least one level improvement in maze test, compared with 0untreated eyes while 5 of the untreated eyes showed at least one level worsening.

“To date, AGTC-501 data show robust improvements in visual function including retinal sensitivity as assessed by MAIA microperimetry and FST,” Pennesi said.2

1. Pennesi M. Subretinal AGTC-501 Gene Therapy for XLRP: 12-Month Interim Safety & Efficacy Results of the Phase 2 SKYLINE Trial. Presented at:
2. Beacon Therapeutics Announces Positive 12-Month Data from Phase 2 SKYLINE Trial of AGTC-501 in Patients with X-Linked Retinitis Pigmentosa. News release. Beacon Therapeutics.
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