Beacon Therapeutics Holdings Limited reported the first patient treatment in its registrational VISTA clinical study evaluating AGTC-501 (laruparetigene zovaparvovec) for the treatment of x-linked retinitis pigmentosa (XLRP).
First, a company rundown.
Beacon Therapeutics was launched by London-based Syncona (a life science investments healthcare company) in June 2023 as an ocular gene therapy company (our coverage here).
- Its focus: Clinical research on three investigational candidates being studied for restoring and improving vision in patients with prevalent and rare blinding retinal diseases:
- XLRP
- Dry age-related macular degeneration (AMD)
- Cone-rod dystrophy (CRD)
And what’s the basis for its research?
The company’s science is centered on using adeno-associated virus (AAV) to “deliver gene constructs that encode therapeutic proteins to address retinal disorders.”
Why use gene therapy?
Three reasons, according to Beacon Therapeutics.
- Easy accessibility
- The company uses subretinal/intravitreal injections and surgical interventions, providing a targeted delivery of AAV vectors intended to strengthen the therapy’s safety and efficacy
- Sustained long-lasting effects are attainable
- These therapeutic genes are internalized into a patient’s retinal cells following delivery, resulting in a sustained and durable treatment effect due to a continuous level of protein expression
- A controlled disease progression
- Beacon Therapeutics noted that gene therapy has already demonstrated an ability to restore mutated genes or genetic factor functions responsible for retinal disorders by targeting the genetic root cause
Gotcha. Now let’s zero in on AGTC-501.
As Beacon Therapeutics’ lead investigational asset, AGTC-501 was originally developed by Applied Genetic Technologies Corporation (AGTC), a publicly-traded biotechnology company developing genetic therapies for rare inherited conditions that was acquired by Syncona in 2022.
What it is: AGTC-501 is a late-stage candidate for XLRP that’s intended to express “the full length RPGR protein, thereby addressing the full complement of photoreceptor damage caused by XLRP, including both rod and cone loss.”
- Note: The asset has already received Fast Track designation by the FDA, as well as:
- Innovative Medicine Designation (ILAP) in the United Kingdom
- Priority Medicine (PRIME) in the European Union
Any clinical research on it so far?
Yes, actually.
Earlier this year, the company released positive 12-month interim safety and efficacy results from the phase 2 SKYLINE trial (NCT06333249)—an expansion (follow-up) to its ongoing phase 1/2 HORIZON trial—on AGTC-501 for XLRP.
The randomized study compared two doses of AGTC-501—high (6.8 E+11 vg/eye) vs low (7.5 E+10 vg/eye)—administered in one eye of 14 male participants (aged 8-50).
And the data?
AGTC-501 demonstrated a 63% response rate in study eyes with a high dose of AGTC-501, with the high-dose participants also demonstrating “a robust improvement in visual function, including mean retinal sensitivity.”
For low dose-treated eyes, the response rate was similar to the untreated fellow eye in the high-dose cohort (0% for both). See our coverage here for more details.
Now this trial.
The randomized, controlled, quadruple-masked, multicenter phase 2/3 VISTA study (NCT04850118) is assessing the safety, efficacy, and tolerability of AGTC-501 administered in two doses (high/low) via subretinal injection in male participants vs an untreated control group (randomized 1:1:1).
- The participants: 75 males (aged 12 to 50)
- Inclusion criteria:
- Best-corrected visual acuity (BCVA) no better than 20/32 and no worse than 20/200 in one eye. See here for more.
- Inclusion criteria:
- The doses:
- Group 1: AGTC-501 (high dose)
- Group 2 AGTC-501 (low dose)
- Group 3: Control
- Note: Participants will be followed for 24 months; after 12 months, they’ll have the option of switching to AGTC-501 (high dose) in the fellow eyes (if eligible)
- Study duration: 5 years
How is bias between groups being minimized?
Beginning at Month 3 of the study, the following assessments will be conducted by evaluators with no knowledge of which participants underwent surgery:
- BCVA
- Low-luminance visual acuity (LLVA)
And what’s being measured?
The primary outcome measure is the number of participants who achieve a ≥15 letter increase from baseline in LLVA, as measured from Day 0 to Month 12.
Secondary outcomes can be viewed here.
Where is this being conducted?
Currently, across three clinical sites in Florida, Ohio, and Texas. Additional sites are expected to open in multiple countries, the company reported.
Bonus: Click here to see if your XLRP patient qualifies for this study.
And when can we expect data?
Per Clinical Trials, the study is expected to conclude by October 2029; interim data will likely be reported before then, though!
So what’s the end goal with this?
Ultimately, Beacon Therapeutics intends to use all long-term data and results from the HORIZON, SKYLINE, and VISTA studies to support an eventual Biologics License Application (BLA) submission to the FDA.