Subretinal delivery of investigational ABBV-RGX-314 for neovascular age-related macular degeneration (nAMD): A phase II pharmacodynamic study

Abstract

Purpose : ABBV-RGX-314 is an investigational single administration gene therapy designed to deliver a transgene for a soluble anti-VEGF Fab. This Phase II bridging study in patients with nAMD evaluated the clinical performance between subretinally delivered ABBV-RGX-314 produced with REGENXBIO’s NAVXpress™ bioreactor platform process and the initial adherent cell culture process.

Methods : This study is a multi-center, open-label pharmacodynamic bridging study to evaluate subretinal delivery of ABBV-RGX-314 produced by either the NAVXpress platform process (BRX) or the adherent cell culture manufacturing process (HS), which was used in the Phase I/IIa trial of ABBV-RGX-314 for the treatment of nAMD. Sixty patients are assigned to one of two dose levels (6.4x10¹⁰ GC/eye or 1.3x10¹¹ GC/eye) with half of the patients receiving BRX and half receiving HS at each dose level (n=15 for each of the four cohorts). ABBV-RGX-314 target protein concentration in the eye at Month 6 is the primary endpoint; safety and tolerability, change from baseline in Best Corrected Visual Acuity (BCVA), change in central retinal thickness (CRT) and need for supplemental anti-VEGF injections are also being evaluated.

Results : All cohorts have fully enrolled. As of May 8, 2023, ABBV-RGX-314 was well tolerated in all cohorts. Five serious adverse events (AEs) were reported, none of which were considered related to ABBV-RGX-314. Through six months in the high dose (BRX and HS; n=30) and low dose (BRX; n=15) cohorts, target protein concentrations in the study eye were similar. These cohorts demonstrated stable-to-improved BCVA and CRT and meaningful reductions in anti-VEGF injection burden, with many injection-free patients. Common treatment emergent AEs through six months were mild-to-moderate and included post-operative conjunctival hemorrhage (38%), post-operative inflammation (31%), and retinal pigmentary changes (13%).

Conclusions : ABBV-RGX-314 produced by the NAVXpress platform process has been well-tolerated and demonstrated a similar clinical profile to the adherent cell culture process. Initial study results support the dose levels and cGMP commercial-ready material being evaluated in the ongoing ATMOSPHERE^® and ASCENT™ pivotal trials.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.