No serious adverse events reported through 24 weeks of a 52 week trial.
A single-injection intravitreal gene therapy that can durably express an intraocular anti-VEGF agent could reduce the need for repeated anti-VEGF injections and improve outcomes for patients with neovascular age-related macular degeneration (nAMD).
A team, led by Charles C. Wykoff, MD, PhD, Director of Clinical Research, Retina Consultants of Houston, presented initial findings at the American Society of Retina Specialists (ASRS) 2020 Virtual Meeting on the safety and biological activity of a novel intravitreal anti-VEGF gene therapy in neovascular age-related macular degeneration.
A single-injection intravitreal gene therapy that can durably express an intraocular anti-VEGF agent could reduce the need for repeated anti-VEGF injections and improve outcomes for patients with nAMD.
In the ongoing phase 1 OPTIC study, the investigators are assessing the safety, tolerability, and efficacy of a single intravitreal injection of ADVM-022.
Included in the multicenter, open-label, multiple cohort, dose-ranging study are patients with nAMD who have demonstrated a response to anti-VEGF therapy, who were administered an intravitreal injection of ADVM-022 t 6x10^11 vg/eye for cohort 1 (n = 6) and at 2x10^11 vg/eye for cohort 2 (n = 6).
The investigators evaluated incidence and severity of adverse events, changes in best corrected visual acuity (BCVA), change in central subfield thickness (CST), and the number of aflibercept rescue injections.
Patients in the first cohort previously received frequent anti-VEGF injections, with a mean of 6.2 injections in the preceding 8 months. This patient population also had relatively good baseline BCVA (mean 65.8 ETDRS letters) and a mean baseline CST of 369.2μm.
The first 24 weeks of the trial have been positive, with no serious adverse events, dose limiting toxicities or non-ocular adverse events related to ADVM-022 reported.
While ocular inflammation was seen in all patients, it occurred most frequently in the anterior segment and was generally mild and manageable with topical steroids. BCVA was also maintained with a mean change of -2.0 ETDRS letters (90% CI, -9.1-5.1). CST improved with a mean change -52.7µm (90% CI, -86.5 to -18.8).
Signs of CNV disease activity on OCT improved or stabilized in the entire patient population, with no rescue injections needed. The study will continue up to 52 total weeks.
“ADVM-022 is designed to provide sustained therapeutic levels of aflibercept following a single intravitreal injection,” the authors wrote. “Patients in cohort 1 of OPTIC treated with a single injection of ADVM-022 were able to maintain vision and improve anatomical outcomes without receiving any rescue aflibercept injections through week 24.”
In a separate study presented at ASRS 2020, researchers showed new data on the treatment burden and vision acuity on anti-VEGF injection patterns for nAMD.
In the study, the investigators reviewed the Level 1 evidence of currently approved anti-VEGF agents, as well as those likely to undergo review by regulatory authorities. The researchers analyzed the anti-VEGF agents and treatment dosing regimen for each study and collected the baseline ETDRS letters, mean number of injections over a 12-month period, and change in ETDRS letters over the course of 12 months.
They analyzed a total of 23 injection regiments from studies involving 6860 eyes, including 8 (31.6%, n = 2165) involving ranibizumab every 4 weeks or pro re nata and 6 (28.6%; n = 1962) involving aflibercept dosed every 4 or 8 weeks.
The study, “Intravitreal Gene Therapy for Neovascular AMD With ADVM-022: Results of the Phase 1 OPTIC Trial,” was published online by ASRS 2020.