The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to Beacon Therapeutics Holdings Limited for its lead investigational asset: laru-zova (AGTC-501), under clinical development for the treatment of x-linked retinitis pigmentosa (XLRP).
First up: Beacon.
Launched in 2023 (see our coverage), the ocular gene therapy company is focused on one goal: Clinically investigating a pipeline of adeno-associated virus (AAV) centered gene therapy candidates for rare retinal diseases such as:
- XLRP
- Dry age-related macular degeneration (AMD)
- Cone-rod dystrophy (CRD)
Why use AAVs: In gene therapy, the AAV (a small virus that infects humans) genome is substituted with “enhanced human therapeutic gene(s), and the AV is subsequently engineered” as a vehicle that precisely delivers therapeutic genes to the retinal cells, according to the company.
Now to this gene therapy candidate.
Laru-zova is designed to express the full length of the retinitis pigmentosa GTPase regulator (RPGR) protein, which plays a key role in both the structure and function of photoreceptor cells and is considered an essential protein for ensuring normal vision.
- In the context of XLRP: Mutations in the RPGR gene are the primary cause for XLRP development.
Back to laru-zova: Expressing the full-length RPGR protein is intended to address “the full complement of [XLRP-induced] photoreceptor damage,” including rod and cone loss.
Nice! Now talk about this designation.
About RMAT: This is part of the FDA’s dedicated expedited program designed for regenerative medicine therapies (including Fast Track and Breakthrough Therapy designations).
- Its purpose: To expedite the development and review process of investigational drug candidates intended to treat, modify, reverse, or cure a serious or life-threatening condition.
Take note: RMAT is based on preliminary clinical evidence indicating a specific therapy could potentially address an unmet need for the condition.
And in the context of laru-zova?
Beacon reported that this designation is based on preliminary clinical evidence recently released from two phase 2 clinical trials that evaluated the gene therapy’s safety, efficacy, and tolerability. (We’ll get to that data in a moment.)
And as CEO Lance Baldo, MD, noted, the company considers this “a significant milestone for the XLRP patient community, and underscores our promising data and the potential for laru-zova to significantly improve the lives of patients who suffer from XLRP.”
As a bonus: Laru-zova has already received FDA Fast Track designation as well as:
- Priority Medicines (PRIME) designation in the European Union
- Innovative Licensing and Access Pathway (ILAP) designation in the United Kingdom
Circle back to those phase 2 trials.
Let’s go over the most recent findings from the ongoing randomized, masked, multicenter phase 2 SKYLINE trial (NCT06333249).
Brief rundown on the setup: 14 males (aged 8-50) diagnosed with XLRP
- The design: Comparison of two laru-zova doses:
- High: 6.8 E+11 vg/eye
- Low: 7.5 E+10 vg/eye
- Each participant administered laru-zova in one eye to evaluate its safety/efficacy
- Main outcome measure (Day 0 to Month 12)
- 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
And the data?
Released in October 2024, 24-month findings included the study meeting its primary endpoint, with the company reporting a response rate of 57% in study eyes treated with the high dose of laru-zova.
- Notably: This was similar to 12-month findings, in which a 63% response rate was demonstrated in study eyes with a high dose of laru-zova.
Sounds promising … and what happened in that second phase 2 trial?
The ongoing non-randomized, open-label, multicenter DAWN study (NCT06275620) is a safety trial also evaluating two doses of laru-zova.
Brief rundown:
- Participants: 24 males (aged 12+) diagnosed with XLRP
- The design: Comparison of three laru-zova doses:
- High with standard corticosteroid regimen
- Low with standard corticosteroid regimen
- High with modified corticosteroid regimen
- Main outcome measure (Day 0 to Month 12):
- Participants experiencing Grade 3 or higher of ocular or non-ocular treatment-emergent adverse events (TEAEs)
What were these findings?
Positive 3-month interim data released in December 2024 found laru-zova to be “well-tolerated by all participants,” according to the company.
- The details: No TEAs were observed—nor any ocular inflammatory AEs.
And importantly: Beacon reported the data indicated “promising early improvements” in low luminance visual acuity (LLVA), which is noted as a critical measure for visual function.
- The DAWN study is currently the first and only in the laru-zova clinical program to collect and evaluate LLVA data.
Sounds promising! So what’s next for the candidate?
With future data readouts still expected from the SKYLINE and DAWN trials (both are expected to conclude in 2027 and 2029, respectively), Beacon is currently enrolling participants for its phase 2/3 VISTA trial.
About that study: This randomized, controlled, masked, multicenter pivotal trial (NCT04850118) is evaluating two study groups receiving two doses of laru-zova against an untreated control group.
As always, stay tuned for updates!