Pooled safety analysis of a single intravitreal injection of JNJ-1887 (gene therapy, AAVCAGsCD59) in patients with age-related macular degeneration (AMD)

Abstract

Purpose : Gene therapy has been evaluated in the treatment of various inherited and common retinal diseases. Immune-mediated and inflammatory responses to gene therapy treatments have been observed across diseases. JNJ-81201887 (JNJ-1887) is a single intravitreal gene therapy injection that expresses soluble CD59 in patients with late-stage AMD. Here, we report the first aggregate safety data from 2 studies of JNJ-1887 in patients with either geographic atrophy (GA) or wet AMD.

Methods : The phase 1 trial 1001 was an open-label, single-center study assessing the safety of JNJ-1887 in patients with GA over 24 months. Patients (N=17) were sequentially enrolled into low (3.56×10¹⁰ vg/eye; n=3), intermediate (1.07×10¹¹ vg/eye; n=3), or high (3.56×10¹¹ vg/eye; n=11) dose groups without corticosteroid prophylaxis. The phase 1 trial 1002 was an open-label, multicenter study assessing the preliminary pharmacodynamic effect and safety of JNJ-1887 in treatment-naïve patients with wet AMD over 12 months. Patients (N=25) received an anti-vascular endothelial growth factor (VEGF) injection followed by a single intravitreal injection of JNJ-1887 at doses of 3.56×10¹¹ vg/eye (n=22) or 1.071×10¹² vg/eye (n=3), with a protocol-defined oral corticosteroid prophylaxis regimen.

Results : Patient characteristics at baseline and concomitant medications were consistent with each disease under study. JNJ-1887 was well tolerated across all cohorts in both studies, with no dose limiting toxicities or serious or systemic adverse events (AEs) related to study intervention. The inflammatory profile in both studies was manageable. In the 1001 study, 5/17 patients experienced mild ocular inflammation, which resolved in 4 patients following either topical steroids or observation. One unresolved event of vitritis, managed with observation, occurred in a patient with an unrelated fatal AE. In the 1002 study, there were 4/25 patients with events of ocular inflammation, all of which were mild or moderate in severity and resolved following a 7-day course of oral steroids and topical steroids of varied duration. In both studies, all exam findings of inflammation were resolved by the time of the patient’s last visit.

Conclusions : JNJ-1887 was well tolerated with a generally favorable safety profile, and the inflammatory profile was manageable in patients with both GA and wet AMD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.