Beacon Therapeutics reported positive topline clinical findings from a registration-enabling study evaluating laruparetigene zovaparvovec (laru-zova) for the treatment of X-linked retinitis pigmentosa (XLRP).
This latest data readout over 2 years after the study’s first participants received a dosing of the investigational gene therapy.
Let’s start with laru-zova.
Before we do, click here for some background on the company—including its focus on developing adeno-associated virus (AAV) centered gene therapy candidates
As for the XLRP asset in question: Laru-zova is built to express full-length retinitis pigmentosa GTPase regulator (RPGR) protein, which plays a key role in the structure and function of photoreceptor cells and is considered essential for normal vision.
- Why it matters for XLRP: Mutations in the RPGR gene are the primary cause of the disease.
The goal: According to Beacon, delivering full-length RPGR is intended to address "the full complement of photoreceptor damage caused by XLRP," including both rod and cone loss.
It’s been a minute since we’ve heard about this asset.
Indeed. In fact, our last coverage was in February 2025, when the FDA granted laru-zova Regenerative Medicine Advanced Therapy (RMAT) designation.
- Check out our full coverage on that—including its significance for the gene therapy’s regulatory pathway.
Also worth noting: Laru-zova has also received Fast Track designation.
So! What have its clinical evaluations looked like so far?
Promising, to say the least, with laru-zova undergoing over 5 years’ worth of investigations across several studies:
- Phase 1/2: HORIZON (NCT03316560)
- Phase 2: SKYLINE (NCT06333249)
- Phase 2: DAWN (NCT06275620)
Talk prior data.
We’ll start with the HORIZON trial.
- The 24-month data: Laru-zova was generally well-tolerated—though all XLRP-diagnosed participants experienced at least one treatment-emergent adverse event (TEAE) associated with the subretinal injection.
- Highest dose (1.99 × 1012 vg/eye) of laru-zova exhibited an unfavorable risk-benefit profile, while preliminary efficacy was observed at the maximum tolerated dose (6.8 × 1011 vg/eye)
- The 36-month data: Laru-zova continued to be generally safe and well-tolerated; the data also demonstrated a difference in visual function between treated and untreated eyes.
And those two phase 2 studies?
Looking at SKYLINE: Beacon released 24-month findings in October 2024, reporting that the trial met its primary endpoint, with a 57% response rate in high-dose eyes. That was in line with the 63% reported at 12 months.
As for the DAWN trial: In 3-month interim results released in December 2024, Beacon said laru-zova was "well-tolerated by all participants," with no [TEAEs — see note] and no ocular inflammatory AEs.
- Also: The company reported "promising early improvements" in low luminance visual acuity (LLVA).
Noted. Now to this latest data—which study is it from?
That would be the Phase 2 VISTA (NCT04850118) study, a randomized, controlled trial (RCT).
- Its purpose: to evaluate the efficacy, safety, and tolerability of laru-zova in 85 male patients (aged 12 to 48) with XLRP caused by mutations in the RP GTPase regulator (RPGR) gene.
- The setup: Participants were divided into two laru-zova dosing groups:
- High dose: 6.8 E+11 vg/eye
- Low dose: 3.7 E+11 vg/eye
- To note: A third control (untreated) group was also followed for the study’s duration
- The duration: 12 months
And what was evaluated?
The outcome measures (tracked from Day 0 to month 12) included:
- Primary: patients with a a ≥15 letter increase from baseline in LLVA
- Importantly, this was endorsed by the FDA
- Secondary: change from baseline in:
- Mean sensitivity across the whole grid, as measured by macular integrity assessment (MAIA) microperimetry
- Full-field stimulus threshold (FST)
See here for more.
Next up: the positive topline data.
Two major findings:
- The study met its primary endpoint
- Laru-zova demonstrated a favorable safety and tolerability profile
- This was consistent with those aforementioned prior trials
Dive a little deeper on this.
Regarding that primary outcome: At month 12, a “statistically significant proportion” of study participants achieved this endpoint (as compared to the untreated control group):
- High-dose group: 31% (p = 0.0019)
- Low-dose group: 24% (p = 0.016)
How about those secondary endpoints?
The positive trends continued: Compared with untreated controls, treated participants improved from baseline in mean macular sensitivity across the full microperimetry grid at Month 12.
More treated participants also gained ≥ 10 letters in LLVA.
What else?
Still sticking with those secondary outcomes:
Also at Month 12: Compared with untreated controls, patients treated with laru-zova gained mean macular sensitivity across the full microperimetry grid:
- 1.31 dB in the low-dose group (p=0.0405)
- 1.20 dB in the high-dose group (p=0.0614).
Plus, more treated patients gained ≥ 10 letters in LLVA:
- 58.6% of the low-dose group (p<0.0001)
- 48.3% of the high-dose group (p=0.0002)
- 3.7% of untreated controls
How about safety and tolerability?
The gene therapy demonstrated a “favorable safety and tolerability profile.”
As for AEs: Mild-to-moderate ocular TEAEs were balanced across both treatment groups— “and largely attributed to the surgical procedure.”
- Among the laru-zova-releated TEAEs: 25% and 38% were reported in the high-dose and low-dose groups, respectively.
- Also worth noting: Two serious ocular AEs were observed in the low-dose group and attributed to “the surgical procedure,” according to Beacon.
Let’s talk big picture.
VISTA is reported to be “the first and only pivotal trial in XLRP to achieve its primary endpoint.”
And because of this, Beacon CEO Lance Baldo, MD, noted: “These results represent a landmark moment for the hundreds of thousands of patients worldwide living with XLRP who currently have no treatment options and no way to slow the loss of their sight.”
Sounds promising … So what's next?
Potential regulatory movement, to say the least.
Following this positive data readout, the company plans to initiate pre-submission discussions with “global regulatory authorities.”
In the United States: A rolling Biologics License Application (BLA) submission to the FDA is planned for “later this year.”
So stay tuned …
Nice! And in the meantime?
The company will share additional data from the VISTA trial next month during the American Academy of Ophthalmology (AAO) annual meeting’s Retina Subspecialty Day.
Details are as follows:
- The session: Subretinal Gene Therapy Laru-zova for X-linked Retinitis Pigmentosa (XLRP): Pivotal VISTA Trial First-time Results
- The date: Saturday, Oct. 10, at 4:13 pm CST
- The presenter: Robert Sisk, MD, FACS, FASRS