ASRS 2023: AAVIATE interim safety study

(Image Credit: AdobeStock/MIND AND I)

Reviewed by David Boyer, MD

The interim 6-month results of the phase II AAVIATE Study evaluating suprachoroidally injected ABBV-RGX-314 neovascular age-related macular degeneration (nAMD) showed that the treatment was well-tolerated and required a lower treatment burden. The few cases of intraocular inflammation that developed resolved with topical steroids.

David Boyer, MD, Adjunct Clinical Professor Ophthalmology Keck School of Medicine, Partner Retina Vitreous Associates Medical Group, Los Angeles, reported the findings at the 2023 annual meeting of the American Society of Retinal Surgeons in Seattle.

Numerous methods have been developed to deliver treatments to the eye, all with different advantages and disadvantages. The suprachoroidal delivery provides targeted access, compartmentalized adeno-associated viral delivery, and facilitates minimal exposure to the vitreous and anterior segment, according to Boyer.

This is in contrast to, for example, delivery to the vitreous chamber, which is associated with broad exposure to the vitreous and anterior segment with a high risk of both an immune response and inflammation.

RGX-314, an investigational formulation being developed in collaboration with AbbVie, may be a potential one-time treatment for nAMD, diabetic retinopathy, and other chronic retinal conditions. The treatment works by inhibiting the vascular endothelial growth factor (VEGF) pathway by which new, leaky blood vessels grow and contribute to fluid accumulation in the retina.

AAVIATE Study

The trial was designed to test 3 escalating doses of AABV-RGX-314 (dose 1, 2.5x1011 genomic copies [GC]/eye; dose 2, 5.0x1011 GC/eye; and dose 3, 1.0x1012 GC/eye) across 5 patient cohorts; the patients did not receive prophylactic steroid during the study. All 95 study patients had been treated previously for nAMD.

The primary goal was to evaluate the mean change in the best-corrected visual acuity (BCVA) with the study drug compared with monthly ranibizumab (Lucentis, Genentech/Roche) injections at 9 months. The secondary goals were to determine the safety/tolerability of ABBV-RGX-314, measure the changes in the central retinal thickness (CRT), and determine the need for anti-VEGF rescue treatment. ABBV-RGX-314 was delivered to the suprachoroidal space during an in-office procedure via a Microinjector.

Interim safety results

Boyer reported that ABBV-RGX-314 was well tolerated in the 5 cohorts during follow-up periods ranging from 1 to 12 months after treatment. Fifteen serious adverse events were reported that were not considered drug-related. No cases of chorioretinal vasculitis or occlusive vasculitis or hypotony developed.

Mild-to-moderate intraocular inflammation was the most frequent ocular adverse effect during the 6 months of the study; others that occurred less often were conjunctival hemorrhage, intraocular pressure increases, conjunctival hyperemia, and episcleritis.

The BCVAs were a few letters better with ranibizumab after patients received 7 injections. In contrast, the numbers of injections in patients treated with ABBV-RGX-314 ranged from a low of 0.7 to a high of 1.6 over the 6-month study period depending on the dose.

The mean CRTs were similar among the patients treated with ranibizumab and the 5 ABBV-RGX-314 cohorts.

A comparison of the numbers of injections before and after ABBV-RGX-314 showed marked decreases after treatment with ABBV-RGX-314, with decreases ranging from -63.8% to -84.7% depending on the cohort.

The investigators added cohort 6 to determine the effect of adding prophylactic ocular steroids. They found that by so doing, the patients in cohort 6 had no case of intraocular inflammation with the short-course of prophylactic topical steroids, Boyer reported.

The take-home messages were as follows:

• The safety profile in the first 5 cohorts showed that the drug was well tolerated in a total of 85 patients.
• The 6-month results in cohorts 1 to 4 treated with ABBV-RGX-314 showed that patients had stable vision and retinal thickness, with a meaningfully reduced treatment burden across all dose levels; the highest reduction in treatment burden seen in cohort 4 (dose 3).
• There was an 85% reduction in the annualized injection rate.
• 67% were injection-free.
• No meaningful differences were seen in patient outcomes with and without baseline AAV8 NAbs.
• Intraocular inflammation resolved with topical corticosteroids; cohorts 1 to 3 that received doses 1 and 2 had mild inflammation and a similar incidence observed across doses; cohort 4 that received dose 3 had mild-to-moderate inflammation and the incidence was increased compared to the previous doses.

“These results are very encouraging and allow physicians to do a safe in-office procedure that will minimize the treatment burden to our patients and their caregivers with minimal inflammation,” Boyer concluded.

David Boyer, MD

E: vitdoc@aol.com

Boyer is Adjunct Clinical Professor of Ophthalmology, Keck School of Medicine, Partner Retina Vitreous Associates Medical Group, Los Angeles. He serves as a consultant to Regenxbio.