REGENXBIO Inc. released additional positive data from its ongoing phase 2 ALTITUDE trial assessing ABBV-RGX-314 for diabetic retinopathy (DR) treatment without center-involving diabetic macular edema (CI-DME) via in-office suprachoroidal delivery.
The results were presented by Mark R. Barakat, MD, Retinal Consultants of Arizona (RCA), during the American Academy of Ophthalmology (AAO) annual meeting on Nov. 5, 2023.
Refresh me on this investigational candidate.
Formerly known as RGX-314, ABBV-RGX-314 is a gene therapy candidate in development that REGENXBIO is evaluating whether it could be administered either through standardized one-time subretinal delivery or via the suprachoroidal space.
Further, the company has acquired certain exclusive rights to the SCS Microinjector from Clearside Biomedical to deliver the gene therapy to the suprachoroidal space.
I’m listening …
The gene therapy leverages a novel adenosine-associated virus (N + AAV= NAV for short) vector, and has the potential to treat patients with retinal diseases.
To note, it’s also currently being investigated for the treatment of chronic retinal diseases like wet age-related macular degeneration (AMD) in patients who might have been administered anti-vascular endothelial growth factor (anti-VEGF) in the past.
So how does this NAV vector work?
The NAV vector is administered via injection or infusion, reaching the target cells and delivering the gene—thus allowing the cells to potentially manufacture the deficient protein(s) for various rare diseases.
And in ABBV-RGX-314?
ABBV-RGX-314 includes the NAV adeno-associated virus 8 (AAV8) vector containing a gene encoding for a monoclonal antibody fragment.
Through protein expression, this modified AAV vector is designed to neutralize VEGF activity, blocking the pathway where new, leaky blood vessels may grow and cause fluid to accumulate in the retina.
REGENXBIO has a number of potential pipeline therapies as part of its NAV Technology Platform.
Let’s back up for a moment: Why the drug name change?
REGENXBIO renamed ABB-RGX-314 as part of transferring its investigational new drug (IND) applications to AbbVie—which it partnered with in 2021 to develop and commercialize ABB-RGX-314—for all nine current and ongoing clinical trials in the United States and Canada, including two pivotal trials.
Gotcha. Now talk about this ALTITUDE trial.
The multicenter, open-label, randomized, observation-controlled, dose-escalation phase 2 trial (NCT04567550) is assessing ABBV-RGX-314 using the SCS Microinjector in 50 patients with moderately severe or severe non-proliferative DR (NPDR) or mild proliferative DR (PDR).
How are the patients divided?
Split into three cohorts:
- Cohort 1
- Patients received ABBV-RGX-314 at a dose level of 2.5x1011 genomic copies per eye (GC/eye) (dose level 1)
- Cohorts 2 and 3
- Patients received ABBV-RGX-314 at an increased dose level of 5x1011 GC/eye (dose level 2).
To note, patients in all cohorts did not receive prophylactic corticosteroid therapy before or after administration of ABBV-RGX-314, according to the company.
And these findings?
Per REGENXBIO, ABBV-RGX-314 was found to be well-tolerated at dose levels 1 and 2.
Also for these dose levels, NPDR patients treated with ABBV-RGX-314 demonstrated “clinically meaningful improvements in disease severity and reduction of vision-threatening events.”
Which dose level was found to mitigate disease progression? ?
At one year, dose level 2 in NPDR patients prevented disease progression, as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (DRSS).
Give me some numbers.
The risk for development of vision-threatening events was reduced by 89% (compared to control) for patients at dose level 2, according to the data. Further for these baseline NPDR patients:
- 100% demonstrated stable to improved disease severity
- 70.8% achieved ≥1 step improvement vs. 25.0% in control
- 0% worsened ≥2 steps vs. 37.5% in control
- 4.2% developed vision-threatening events vs. 37.5% in control
Let's get some expert insight.
Per Dr. Barakat, the ALTITUDE trial’s positive data is promising, given the unmet need for sustainable treatment in DR and PDR, as well as the development of vision-threatening complications over the longer term.And according to REGENXBIO Chief Medical Officer Steve Pakola, MD: "A one-time, in-office injection of ABBV-RGX-314 gene therapy has the potential to stabilize and improve DR severity score and reduce the long-term risk of vision-threatening events."
So what’s next?
REGENXBIO will host a conference call regarding the recent trial data on Nov. 6, 2023, at 8:30 am EST. Registration for the webcast can be accessed here.
And as far as new data goes?
The ALTITUDE trial is ongoing, with Clinical Trials reporting a 2024 completion.
Stay tuned in the meantime for additional coverage of their data readouts!
The American Academy of Ophthalmology annual meeting is being held Nov. 3-6 2023, in San Francisco, California.