Beacon Therapeutics Holdings Limited reported 24-month interim safety and efficacy findings from the phase 2 SKYLINE trial evaluating its lead investigational asset for the treatment of x-linked retinitis pigmentosa (XLRP).
First, this company's science.
Launched in June 2023, the ocular gene therapy company’s platform is investigating adeno-associated virus (AAV)-centered gene therapy candidates for the following rare retinal diseases:
- XLRP
- Dry age-related macular degeneration (AMD)
- Cone-rod dystrophy (CRD)
To note: Over the summer, Beacon Therapeutics raised $170 million in funding to support the ongoing clinical development of AGTC-501.
Now the XLRP candidate.
AGTC-501, the company’s lead gene therapy program, is a late-stage candidate targeting XLRP—a disease primarily caused by mutations in the RP GTPase regulator (RPGR) gene.
How it works: The asset expresses the full-length RPGR protein to “address the full complement of photoreceptor damage” caused by XLRP—which includes both rod and cone loss.
Next: The study.
Initiated as an expansion to an ongoing phase 1/2 study (HORIZON), the randomized, masked, multicenter phase 2 SKYLINE trial (NCT06333249) was set up with the following:
- Participants: 14 males (aged 8-50) diagnosed with XLRP
- The design: Comparison of two AGTC-501 doses:
- High: 6.8 E+11 vg/eye
- Low: 7.5 E+10 vg/eye
- The administration: Each participant administered AGTC-501 in one eye to evaluate its safety/efficacy
- The outcome measures (from Day 0 to Month 12)
- Primary: Difference in responding eyes between treated and control eyes in the low / high dose groups at Month 12, as measured via macular integrity assessment (MAIA) microperimetry
- Secondary: See here
And the 24-month findings?
To start, the study met its primary endpoint, with the company reporting a response rate of 57% in study eyes treated with the high dose of AGTC-501.
- To note, the response rate was defined as a “7 (decibels) dB or more improvement in at least 5 loci.”
Further: High-dose cohort patients also demonstrated robust improvement in mean retinal sensitivity.
How about among low-dose-treated patients?
Among this cohort, participants demonstrated a response rate of 25%.
Any adverse events reported?
Beacon Therapeutics reported no clinically significant safety events associated with AGTC-501 treatment, while treatment-emergent adverse events (TEAEs) were notably non-serious and mild to moderate in severity.
To note: In general, AGTC-501 was found to be safe and well-tolerated.
This sounds promising … how does it compare to prior phase 2 data?
Back in February 2024, the company reported positive 12-month results from the SKYLINE trial.
The crux of those findings:
- A 63% response rate was demonstrated in study eyes with a high dose of AGTC, with that cohort also exhibiting a “robust improvement in visual function,” including mean retinal sensitivity.
- The response rate was similar to the untreated fellow eye in the high dose cohort (0% for both) among low-dose-treated eyes.
Nice! Anything else to take note of?
Indeed there is … a more in-depth look at these 24-month findings will be presented during this weekend’s American Academy of Ophthalmology (AAO) annual meeting (Oct. 18-21) in Chicago, Illinois.
Those details:
- Poster:
- Subretinal AGTC-501 Gene Therapy for XLRP: 24-Month Interim Results of the Phase 2 SKYLINE Trial
- Presenter:
- Robert Sisk, MD, FACS, FASRS
- Associate Professor of Ophthalmology at the University of Cincinnati
- Vitreoretinal surgeon and partner at Cincinnati Eye Institute
- Director of Pediatric Retinal Surgery at Cincinnati Children’s Hospital
- Director of Ophthalmic Genetics at Cincinnati Children’s Hospital
- Robert Sisk, MD, FACS, FASRS
And the plan moving forward?
The company has already initiated patient enrollment in two XLRP-focused studies:
- Pivotal phase 2/3 VISTA (NCT04850118)
Open-label phase 3 DAWN trial (NCT06275620)