Mark R. Barakat, MD: RGX-314 for Diabetic Retinopathy in ALTITUDE Study


First-year results from ALTITUDE suggest RGX-314 was well-tolerated and provided meaningful improvements in disease severity at dose levels 1 and 2.

A one-time in-office injection of investigational ABBV-RGX-314 led to clinically meaningful improvements in disease severity and a reduction in vision-threatening events in patients with non-proliferative diabetic retinopathy (NPDR), according to one-year results from the phase 2 ALTITUDE study.

The data, presented at the 127th Annual American Academy of Ophthalmology (AAO) Meeting in San Francisco, California, showed dose level 2 of RGX-314 prevented disease progression in all patients with NPDR, with approximately 70% of patients achieving any disease improvement.

“Diabetic retinopathy is such an exciting area for gene therapy because it’s a chronic disease,” Mark Barakat, MD, Retina Consultants of Arizona, told HCPLive. “Either we do what we do right now, wait for them to get worse before we intervene, or we could possibly put them on anti-VEGF injections to reduce the risk of vision-threatening events. Whereas this could be a one-and-done in-office procedure.”

The high treatment burden of diabetic retinopathy leads many patients with early stages to remain untreated, despite therapy’s ability to modify and prevent disease progression. This is particularly apparent in moderate non-proliferative diabetic retinopathy (NPDR) and severe NPDR, which leads to high rates of PDR and DME within 5 years.

According to Barakat, the goal of a 1-time, in-office injection of gene therapy is to stabilize disease severity and potentially provide long-lasting improvement in diabetic retinopathy severity while reducing the risk of vision-threatening complications. RGX-314 is an AAV8 vector encoding a monoclonal antibody fragment with the potential for long-term anti-VEGF therapeutic expression.

ALTITUDE is a phase 2 trial of patients with moderately severe NPDR, severe NPDR, and mild PDR without active center-involved DME. They get a single injection of suprachoroidal RGX-314 on day 1 and are followed for 1 year, with standard-of-care treatment, as needed. The primary endpoint was ≥2-step improvement in DRSS scores, with Barakat focusing on cohorts 1-3, representing dose levels 1 and 2 (n=50).

At year 1, dose levels 1 and 2 were well-tolerated, with 7 serious adverse events (SAEs) not considered related to the drug. There were no cases of chorioretinitis, vasculitis, occlusion, or hypotony. There were cases of mild-moderate episcleritis (12%) and intraocular inflammation (6.0%), controlled with topical therapy.

In the control group (n=8) at 1 year, more patients (37.5%) experienced ≥2-step DRSS worsening than ≥2-step improvements (12.0%). In the RGX-314 dose level 1 cohort (n=6), more patients (33.3%) experienced ≥2-step improvement at 1 year, than worsening (16.7%). In RGX-314 dose level 2 (n=24), no patients experienced 2-step worsening, and 20.8% experienced ≥2-step improvement at 1 year.

Overall, any improvement was measured at 25.0% in control, 66.7% in RGX-314 dose level 1, and 70.8% in RGX-314 dose level 2. Regarding safety, vision-threatening events were reduced by 89% from control to RGX-314 dose level 2 through 1 year: 37.0% in control, 16.7% in RGX-314 dose level 1, and 4.2% in RGX-314 dose level 2.

For more insight into the one-year study results, watch the full interview with Dr. Barakat.


Barakat M. Suprachoroidal Delivery of Investigational ABBV-RGX-314 for Diabetic Retinopathy: The Phase II Altitude Study Dose Levels 1 and 2: One-Year Results. Presented at the 2023 American Academy of Ophthalmology Annual Meeting, November 3 – 6, 2023.

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