Abstract
Purpose:
To evaluate the safety and clinical response to two doses of NT-503 Encapsulated Cell Therapy (ECT) for the treatment of choroidal neovascularization in AMD over a 24 month period. The NT-503 ECT implant continuously releases a soluble vascular endothelial growth factor receptor (VEGFR) protein into the vitreous cavity for at least 2 years.
Methods:
This is an on-going, open-label, dose-escalation study. Twenty-six patients in the per-protocol population received a single, ECT implant (releasing 2.0-2.5 μg/d of VEGFR) and 21 patients received two ECT implants (releasing 4.0-5.0 μg/d of VEGFR). Safety and clinical response measures collected during the study include best-corrected ETDRS visual acuity and retinal thickness from registered sd-OCT images read by masked graders at the Duke Reading Center. The need for rescue therapy with ranibizumab, based upon predefined OCT or vision criteria, is also being evaluated.
Results:
There was a clear dose response with two implants, achieving greater numerical improvements in visual acuity and reductions in macular thickening. With two implants, there was an improvement in median BCVA of ≥ ~10.0 ETDRS letters from month 12 out to 20 months, the last visit with available data. Median macular thickening improved >~170 microns from month 12 to month 20. To date, 11 of 26 (42.3%) with a single implant and 4 of 21 (19.0%) with double implants required rescue therapy after implantation. Most adverse events were related to the surgical procedure, concurrent ocular conditions, or unrelated conditions. There were no cases of treatment-related cataract or infectious endophthalmitis, or treatment discontinuations.
Conclusions:
NT-503 ECT was well tolerated and a dose response was observed. Clinically meaningful improvements in visual acuity and reductions in macular thickening were observed in patients receiving two NT-503 ECT implants out to at least 20 months, thereby establishing a proof of concept for the long-term therapeutic potential of NT-503 in AMD and for the ECT platform. A next-generation single, multi-chamber device, which achieves a 2-3 fold increase in VEGFR production over that achieved with the two implants tested in this study, and which can support combination therapy, is being evaluated in a randomized, masked clinical trial versus aflibercept (Eylea®) dosed on label every 8 weeks.