REGENXBIO Inc. released positive findings from a phase 2 fellow eye sub-study investigating its gene therapy candidate ABBV-RGX-314 for the treatment of patients with bilateral wet age-related macular degeneration (AMD).
The data was presented during this past weekend’s annual American Academy of Ophthalmology (AAO) meeting in Chicago, Illinois.
First things first: Talk science to me.
Before we get into the nitty gritty on ABBV-RGX-314, you need to understand what it’s based on.
The answer: The candidate utilizes a novel (N) adenosine-associated virus (AAV) vector known as a NAV vector—the foundation for RegenxBio’s NAV Technology Platform.
- The platform: Encompasses 100+ novel AAV vectors—with some specifically intended to target certain areas of the human body in need of a gene the most.
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: Triggering 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.
Then: 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 ABBV-RGX-314 fits into this.
The candidate is currently in clinical development as a potential one-time, subretinal (or suprachoroidal space [SCS] 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 (our topic of choice)
- Diabetic retinopathy
- 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.
Via 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.
Moving on to the clinical data.
Our topic of interest—this phase 2 sub-study—evaluated the safety and efficacy of ABBV-RGX-314 administered as a single dose (1.3x1011 GC/eye) via subretinal delivery in the fellow eye of patients previously treated in the company’s phase 1/2a dose-escalation study.
About that initial study:
- Participants: 42 wet AMD patients (aged 50-89) with a history of anti-VEGF injections
- Design: Patients divided into five cohorts, with each receiving one of five different injection doses of ABBV-RGX-314
- The follow-up: All participants were observed post-injection on a monthly basis for 2 years
- The primary outcome: Safety of ABBV-RGX-314 (via ocular/nonocular adverse events (AEs) up to 26 weeks
And the findings from that dose-escalation study?
Stable or improved vision and retinal anatomy were observed up to 2 years in patients treated with ABBV-RGX-314.
- The gene therapy was generally well-tolerated with a sustained VEGF-A suppression in wet AMD patients and the potential to “control exudation, maintain vision, and reduce treatment burden after a single administration.”
Alrighty, back to this sub-study.
Following administration of that 1.3x1011 GC/eye dosage of ABBV-RGX-314 in the fellow eye of patients, the second eye was treated with the gene therapy an estimated +1 year later.
And the data: Nine-month findings encompassed nine participants who received ABBV-RGX-314 via subretinal delivery in the phase 1/2a or “bridging studies” as well as who chose to receive treatment in their second eye.
- Important to note: These patients also had “a high treatment burden in the fellow eye” and previously received (on average) nine anti-VEGF injections in the year prior to entering the study—including anti-VEGF injections intended to be longer-lasting treatments.
Next up: This new data.
At the 9-month post-administration point, the following was reported:
- 97% reduction in annualized anti-VEGF treatment burden
- 100% of patients required either one or zero supplement injection
- 78% of patients were completely injection-free
And in terms of visual acuity?
Sustained best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were demonstrated at the 9-month mark—with ABBV-RGX-314 producing “similar levels of aqueous protein in both treated eyes.”
How about adverse events?
RegenxBio reported that, as of Sept. 11, 2024, the gene therapy was “well tolerated” in the treated fellow eyes and was not associated with any drug-related serious adverse events (AEs).
In fact, common AEs observed were mild retinal pigmentary changes, which developed in “periphery and post-operative conjunctival hemorrhage.”
- Notably, these were resolved within days to weeks.
Go on ...
There were also no reported cases of:
- Intraocular inflammation
- Chorioretinitis
- Vasculitis
- Occlusion
- Hypotony
RegenxBio also reported that—aside from those generally used in vitrectomy surgery—no prophylactic steroids were utilized in the trial.
So what did the company have to say about this?
President and CEO Curran Simpson noted the significance of this sub-study, calling it “the first to evaluate a gene therapy in fellow eyes for wet AMD” as well as further supporting data to add on to the candidate’s previous clinical findings.
Arshad Khanani, MD, MA, FASRS, director of Clinical Research at Sierra Eye Associates, Reno, Nevada, as well as the presenter of these findings, further emphasized ABBV-RGX-31 as a promising treatment.
“This is the first time we have performed bilateral treatment for wet AMD patients,” he stated. “These results, combined with the durable treatment effect up to 4 years shown in long-term follow up, highlight the potential of ABBV-RGX-314 as a one-time effective treatment option for patients with wet AMD."
Lastly, what if I want to see more details on this research?
Click here to view Dr. Khanani’s AAO 2024 presentation.