Beacon Therapeutics’ XLRP Gene Therapy AGTC-501 Continues to Show Favorable Benefit-Risk Profile at 36 Months

Beacon Therapeutics’ AGTC-501, an investigational adeno-associated virus (AAV) vector-based gene therapy being evaluated for the treatment of X-linked retinitis pigmentosa (XLRP), has continued to show a favorable benefit-risk profile in the view of the company, based on newly updated data from the phase 1/2 HORIZON clinical trial (NCT03316560).¹ The data were presented at the 24th EURETINA Congress held September 19 to 22, 2024, in Barcelona, Spain.

In terms of safety, there were no suspected unexpected serious adverse reactions (SUSARS) and no endophthalmitis observed among 29 patients treated in the study. Furthermore, most treatment-emergent adverse events (TEAEs) were characterized as not serious. There were 7 ocular serious AEs (SAEs) in total, including 4 cases of retinal detachment, 1 case of subcapsular cataract, and 1 case of reduced visual acuity, all of which were considered related to the injection procedure, and 1 case of glaucoma considered related to perioperative steroids. Notably, participants in the trial were treated with AGTC-501 either centrally or peripherally; 3 of the 4 cases of retinal detachment occurred in patients who received the gene therapy peripherally. There were no SAEs deemed related to AGTC-501 itself. Beacon additionally pointed out that according to Kaplan-Meier survival curves, approximately 73% of the ocular TEAEs took place during the first 3 months posttreatment and the majority of TEAEs resolved within a month after appearing.

Nonserious AEs reported in the study included cataract nuclear, conjunctival hyperaemia, increased intraocular pressure, lens disorder, and retinal depigmentation, all of which occurred in 1 patient each. Of these, only retinal depigmentation was deemed possibly related to AGTC-501 and possibly related to the injection procedure. All grade 3 or higher AEs were reported to have resolved, excepting the cases of retinal depigmentation, reduced visual acuity, and cataract nuclear.

With regard to efficacy, a post-hoc analysis focused on microperimetry was carried out on a set of 10 patients who met the inclusion criteria for SKYLINE, a separate phase 2 clinical trial (NCT04850118) evaluating AGTC-501 in XLRP. According to Beacon, the data indicated that an improvement in visual function between treated and untreated fellow eyes continued to be seen at 36 months posttreatment, in line with earlier findings.²

“This emerging longer-term data is another clinical validation of the safety of AGTC-501 for the treatment of XLRP,” Lance Baldo, MD, the chief executive officer of Beacon, said in a statement.² “We look forward to achieving several upcoming clinical milestones, including 24-month data from the phase 2 SKYLINE trial in XLRP later this year, and continued enrollment into our open-label phase 2 DAWN trial and Phase 2/3 VISTA trial.”

Beacon reported 12-month data from the SKYLINE trial earlier this year at the 47th Annual Maula Society Meeting, held Feb 07 - 10, 2024, in Palm Springs, California.³ The data came 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) of AGTC-501. 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 5 loci at month 12. There were no ocular SAEs that were considered related to the gene therapy.

"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,” Nadia Waheed, PhD, the chief medical officer of Beacon Therapeutics, said in a statement.⁴

REFERENCES
1. Yang P, Lauer A, Birch DG, et al. Subretinal gene therapy drug AGTC-501 for X-linked retinitis pigmentosa (XLRP) phase 1/2 multicenter study (HORIZON): 36-month interim results. Presented at: the 24th EURETINA Congress held September 19 to 22, 2024, in Barcelona, Spain.
2. Beacon Therapeutics presents 36-month interim results from phase I/2 HORIZON trial of AGTC-501 in patients with XLRP. News release. Beacon Therapeutics Holdings Limited. September 19, 2024. Accessed September 24, 2024. https://www.beacontx.com/news-and-events/beacon-therapeutics-presents-36-month-interim-results-from-phase-i-2-horizon-trial-of-agtc-501-in-patients-with-xlrp/
3. Pennesi M. Subretinal AGTC-501 Gene Therapy for XLRP: 12-Month Interim Safety & Efficacy Results of the Phase 2 SKYLINE Trial. Presented at:https://www.beacontx.com/news-and-events/subretinal-agtc-501-gene-therapy-for-xlrp-12-month-interim-safety-efficacy-results-of-the-phase-2-skyline-trial/
4. 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. February 8, 2024. Accessed September 24, 2024. https://www.prnewswire.com/news-releases/beacon-therapeutics-announces-positive-12-month-data-from-phase-2-skyline-trial-of-agtc-501-in-patients-with-x-linked-retinitis-pigmentosa-302056840.html