ADVM-022 Gene Therapy for nAMD May Reduce Anti-VEGF Injection Burden


The single-injection investigative gene therapy may help with providing continuous expression of aflibercept.

gene therapy

Brandon Busbee, MD

New data from the Association for Research in Vision and Ophthalmology (ARVO) Virtual Meeting demonstrates safety and efficacy of gene therapy ADVM-022 in patients with neovascular age-related macular degeneration (nAMD).

These findings are from the Phase 1 OPTIC trial, an open-label, multicenter, dose-ranging study designed to evaluate the safety, efficacy, and tolerability in patients who have previously received and shown response to anti-VEGF therapy.

“Intravitreal gene therapy has the potential to significantly reduce treatment burden and improve vision outcomes in patients with neovascular AMD,” noted the study investigators.

Led by Brandon Busbee, MD, of Tennessee Retina, the investigative team administered 2 different intravitreal doses of the gene therapy across 4 cohorts. Furthermore, they measured incidence and severity of adverse events, change in visual acuity (BCVA), change in central retinal thickness (CST), as well as need for and number of supplemental aflibercept injections.

In the study, cohorts 1 (n = 6) and 4 (n = 9) received 6x1011 vg/eye while cohorts 2 (n = 6) and 3 (n = 9) received 2x1011 vg/eye. Patients in cohort 1 were followed up for a median of 86 weeks, patients in cohort 2 for a median of 64 weeks, cohort 3 for a median of 48 weeks, and cohort 4 for a median of 16 weeks.

All patient across cohorts received mean 7.1-9.2 injections of anti-VEGF in the 12 months prior to the study. Notably, such injections led to decent baseline BCVA (mean, 65.0-65.9 letters) before commencing ADVM-022 treatment.

Thus, Busbee and team reported that the gene therapy was well-tolerated across cohorts; it further demonstrated a favorable safety profile.

Reported ocular events related to the therapy were rated as mild in 78% of cases and moderate in 22% of cases. Any ocular inflammation was shown to subside with steroid eye drops. The investigators also reported no cases of retinal involvement.

As for general efficacy, both doses of gene therapy were linked with a significant reduction in anti-VEGF injection burden. Of the 15 who received the higher dose and 15 who received the lower dose, 14 and 10, respectively, did not require anti-VEGF supplementation.

Even more, mean annualized anti-VEGF injection frequency was reduced by 99% in the higher dose cohorts and 85% in the lower dose cohorts after treatment.

In cohorts 1-3, BCVA was maintained with an overall mean age change from -2.5 to 0.5 ETDRS letters. Patients demonstrated a CST mean change from -19.7 to -132.7 µm. Data from cohort 4 is currently pending.

“Over 80% of patients with nAMD treated with a single injection of ADVM-022 in OPTIC have not needed any supplemental anti-VEGF injections up to 92 weeks follow-up,” Busbee and colleagues emphasized. “ADVM-022 has the potential to reduce treatment burden and improve patient vision outcomes.”

The study, “Phase 1 Study of Intravitreal Gene Therapy with ADVM-022 for neovascular AMD (OPTIC Trial),” was presented at ARVO 2021.

Despite these promising results, the future for ADVM-022 remains unclear. In late April, Adverum, the company developing the gene therapy, announced the discovery of a suspected unexpected serious adverse reaction of hypotony with panuveitis and loss of vision in a patient with diabetic macular edema treated in the phase 2 INFINITY trial. This adverse event is currently under exploration to uncover a potential cause.

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