Beacon Therapeutics’ XLRP Gene Therapy AGTC-501 Continues to Show Promise in Long-Term Data From SKYLINE Trial

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 promising efficacy and safety in 24-month follow-up data from the phase 2 SKYLINE clinical trial (NCT04850118).¹

For the purpose of the trial, response to treatment was defined as improvement in retinal sensitivity at least 7 decibels in at least 5 loci; measurement was carried out by microperimetry. Among 7 patients’ eyes that were treated with the study’s high dose, which constitutes 6.8x10¹¹ vg/eye, the response rate was 57% (4/7 eyes). On the other hand, among 4 patients’ eyes that were treated with the lower dose in the trial (7.5x10¹⁰ vg/eye), the response rate was 25% (1/4 eyes). Beacon noted that “robust improvement” in mean retinal sensitivity was observed in patients who received the high dose. In terms of safety, no clinically significant safety events were associated with AGTC-501. Treatment-emergent adverse events were mostly characterized as nonserious and mild to moderate with regard to severity.

“Our phase 2 SKYLINE 24-month data reinforces AGTC-501’s favorable safety profile and robust improvements in mean retinal sensitivity,” Lance Baldo, MD, the chief executive officer of Beacon Therapeutics, said in a statement.¹ “We will continue to assess the long-term safety and durability of AGTC-501 but are encouraged by the results we’ve seen in the SKYLINE trial to date.”

Notably, AGTC-501 is also being evaluated in several other clinical trials. According to the company, the phase 2/3 VISTA and phase 2 DAWN clinical trials (NCT06275620) are currently recruiting patients. On the other hand, the phase 1/2 HORIZON clinical trial (NCT03316560), which is also evaluating AGTC-501, is active, but no longer recruiting patients.

Notably, the first patient in VISTA was treated in June 2024.² At the time, the company noted that its expects that data from VISTA, HORIZON, and SKYLINE will ultimately support a biologics license application for the gene therapy in the United States and a marketing authorization application in the European Union.

“This is an important milestone for the continued clinical development of AGTC-501, which offers the potential to transform the prognosis of patients with XLRP by enabling them to see better or maintain their current vision,” Darin Curtiss, PharmD, the global vice president of clinical development at Beacon, said in a June 2024 statement.² “We look forward to progressing AGTC-501 in the clinic and moving toward our goal of bringing a treatment to market for this life-altering disease.”

Data from HORIZON were recently presented at the 24th EURETINA Congress held September 19 to 22, 2024, in Barcelona, Spain.³ 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. 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.⁴

“This emerging longer-term data is another clinical validation of the safety of AGTC-501 for the treatment of XLRP,” Baldo said in a September 2024 statement.⁴ “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.”

Although AGTC-501 is Beacon’s only gene therapy product currently in clinical trials, the company has several other programs in preclinical development.⁵ One of these is an AAV vector-based gene therapy that is to be delivered intravitreally for the treatment of dry age-related macular degeneration. The other is a program intended to treat cone-rod dystrophy, which is caused by a loss-of-function mutation in the CDHR1 gene.

REFERENCES
1. Beacon Therapeutics announces positive 24-month data from phase 2 SKYLINE trial of AGTC-501 in patients with X-linked retinitis pigmentosa. News release. Beacon Therapeutics Holdings Limited. October 15, 2024. Accessed October 16, 2024. https://www.beacontx.com/news-and-events/beacon-therapeutics-announces-positive-24-month-data-from-phase-2-skyline-trial-of-agtc-501-in-patients-with-x-linked-retinitis-pigmentosa/
2. Beacon Therapeutics treats first patient in VISTA registrational trial for AGTC-501. News release. Beacon Therapeutics Holdings Limited. June 12, 2024. Accessed October 16, 2024. https://www.beacontx.com/news-and-events/beacon-therapeutics-treats-first-patient-in-vista-registrational-trial-for-agtc-501/
3. 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.
4. 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 October 16, 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/
5. Pipeline. Beacon Therapeutics. Website. Accessed October 16, 2024. https://www.beacontx.com/pipeline/