RegenxBio Inc. recently announced that the first patient was dosed in the phase 2b/3 NAAVIGATE trial of surabgene lomparvovec (sura-vec, ABBV-RGX-314) in diabetic retinopathy (DR) using suprachoroidal (SC) delivery.
Give me a refresher on RegenxBio.
Founded in 2009 and headquartered in Rockville, Maryland, RegenxBio is a biotechnology company focused on advancing a late-stage clinical pipeline of gene therapies for rare and retinal diseases, such as:
- Retinal disease (ABBV-RGX-314):
- Neuromuscular diseases (RGX-202)
- Duchenne muscular dystrophy (DMD)
- Neurodegenerative diseases (RGX-121)
- Mucopolysaccharidosis type II (MPS II)
Note: RegenxBio also selectively licenses its proprietary NAV vectors to other biotechnology companies— including the first FDA-approved (in 2019) gene therapy utilizing NAV Technology for the treatment of spinal muscular atrophy (ZOLGENSMA, Novartis).
Tell me more about this NAV Technology.
Sura-vec utilizes a novel (N) adenosine-associated virus (AAV) vector known as a NAV vector as the foundation for RegenxBio’s NAV Technology Platform, which encompasses 100+ novel AAV vectors, including AAV8, AAV9, and AAVrh10.
Bringing in this vector: NAV gene therapy works to correct defects in genetic disease (ie: retinal)—which, the company has noted, are typically caused by a single defective gene—by delivering a healthy, working copy of the gene to the cells needing repair.
- The intended result: activating production of the deficient protein within the body.
Then what happens?
After this triggering, the NAV vector is then administered to a patient via injection or infusion—ideally making its way to cells in need of the protein, according to the company.
Following that: The vector is “designed to reach the target cells and deliver the gene it is carrying”—thus allowing the cells to make that protein the body needs.
- The potential of this: These genes could correct a disease (such as AMD) by either:
- Triggering the production of a therapeutic protein
- Allowing the body’s natural mechanisms to kick in
See here for the company’s pipeline investigational candidates featuring the NAV Technology Platform.
Interesting ... now explain how sura-vec fits into this.
The candidate is currently in clinical development as a potential one-time, suprachoroidal space (SCS) (or subretinal delivery, depending on the indication) injection treatment for patients who previously demonstrated a meaningful response to anti-vascular endothelial growth (VEGF) and are diagnosed with one of the following;
- Wet AMD
- DR
- Other chronic retinal conditions.
To note: Its development is courtesy of a partnership between RegenxBio and AbbVie.
Also: For ABBV-RGX-314 administered via SCS delivery, RegenxBio has acquired certain exclusive licensing rights to Clearside Biomedical, Inc.’s SCS Microinjector.
And its mechanism of action?
In relation to that NAV technology platform and vector process: ABBV-RGX-314 includes the NAV AAV8 vector, which contains a gene encoding for a monoclonal antibody fragment.
Through protein expression—in other words, that lengthy process we just described—this modified AAV vector is designed to neutralize VEGF activity and block the pathway where new, leaky blood vessels may grow and cause fluid to accumulate in the retina.
Gotcha. Now talk about this NAAVIGATE trial.
The phase 2b/3 multicenter, randomized, masked, sham-controlled study (NCT07592273) is designed to evaluate the safety and efficacy of sura-vec in subjects with non-proliferative DR (NPDR) without center-involved diabetic macular edema (DME).
Participants will receive sura-vec at 1.0x1012 genome copies (GC)/eye, which was evaluated as dose level 3 in the phase 2 ALTITUDE trial (NCT04567550) of sura-vec, and short-course topical prophylactic steroids.
- The estimated primary completion date: June 2028.
What’s the setup?
NAAVIGATE will consist of three portions: a phase 2b, phase 3, and bilateral treatment portion, with ~135 participants enrolled in the phase 2b portion and ~576 adult participants expected to be enrolled in the entire study across multiple sites in the United States and Puerto Rico.
- Plus: In all three portions follow-up in the study will continue through 5 years following administration of sura-vec in each eye.
And the primary outcome measures?
The primary endpoint is ≥ 2-step improvement from baseline on the DR severity scale (DRSS) at 1 year.
For the bilateral portion, the primary outcome measure will be the number of participants who experience:
- Ocular adverse events (AEs)
- Serious AEs (SAES)
- Any AEs of special interest (AESIs)
- Intraocular inflammation
- Scleral inflammation including episcleritis
Anything else we should know?
Indeed: RegenxBio will receive $100 million from AbbVie for this milestone.
Noted. So how has the candidate performed in prior clinical evaluations?.
In 2-year dose level 3 data from the ALTITUDE trial, sura-vec demonstrated a durable efficacy profile and was well-tolerated with no intraocular inflammation observed (n=15).
Importantly: This data supported the potential for an in-office gene therapy approach.
Any comments from the company?
“A one-time, in-office treatment has the potential to transform DR management by improving long-term outcomes while making earlier intervention both practical and scalable for patients worldwide,” explained Arshad Khanani, MD, MA, FASRS, director of Clinical Research at Sierra Eye Associates.
Dr. Khanani has been involved in RegenxBio’s clinical trial investigations.
So … when can we expect an update from this latest study?
The company plans to present findings from two separate wet AMD studies at next week’s American Society of Retina Specialists (ASRS) 44th Annual Meeting in Montreal, Canada:
- 2.5-year data from the long-term follow-up study of the ALTITUDE trials
- 5-year long-term follow-up data from a phase 1/2a study
Plus: RegenxBio also expects to announce topline data with AbbVie from the ATMOSPHERE (NCT04704921) and ASCENT (NCT05407636) pivotal trials of sura-vec using subretinal delivery in Q4 2026.