AAO 2023: ALTITUDE Phase II One Year Results of RGX-314

Jovi C.Y. Wong, MD, MSc, DPhil
University of Toronto

At AAO 2023 Retina Subspecialty Day 1, the most anticipated session of the afternoon was the Late Breaking Developments (Part 1), which kicked off with the session entitled “ALTITUDE: Suprachoroidal Delivery of ABBV-RGX-314 Investigational Gene Therapy for Diabetic Retinopathy.“ This presentation revealed the results of the Phase II one year results of the ALTITUDE trial. 

Dr. Mark Barakat from the Retinal Consultants of Arizona presented these new findings from the ALTITUDE trial of ABBV-RGX-314, a novel AAV8 vector-delivered antibody fragment designed to inhibit VEGF that is administered in a one time in-office suprachoroidal injection for the treatment of diabetic retinopathy without center-involved diabetic macular edema. This multi-center, open-label randomized control trial includes dose-escalation to evaluate safety and efficacy in a cohort of 50 treated patients. Dose level 1 refers to a dose level of 2.5×1011 genomic copies per eye (GC/eye) and Dose level 2 refers to 5×1011 GC/eye. 

Dr. Barakat reported that at one year post-administration, Dose level 2 patients (n=24) with baseline NPDR had 100% stable to improved disease severity. BCVA remained stable in all patients with Dose 1 and Dose 2 both well tolerated. 70.8% of treated patients achieved greater or equal to one ETDRS step improvement compared to 25% of control patients. 0% of treated patients worsened 2 or more ETDRS steps, compared to 37.5% of control patients. He highlighted that Dose level 2 also reduced the risk of developing vision-threatening events by 89% (4.2% of treated patients, 37.5% of controls). 

In terms of safety, Dr Barakat stated that no chorioretinitis, vasculitis, occlusion or hypotony was reported. There were 7 serious adverse events, and none were considered related to treatment. Mild intraocular inflammation was reported in 3 patients (6%), whereas 6 patients (12%) had mild to moderate episcleritis and all resolved with topical corticosteroids.

Following the presentation of these findings there was a short discussion with questions regarding how we expect to incorporate this novel, long-lasting treatment into current clinical practice. Another question raised concerns regarding offering young patients a “one and done” treatment given unknown long lasting effects and possible variable systemic glucose control. Dr. Barakat answered both questions with the assertion that he expects that this therapeutic could be offered to a majority of diabetic retinopathy patients and reduce the burden of multiple anti-VEGF treatments.