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Anat Loewenstein, Hugo Quiroz-Mercado, Jose Luis Guerrero-Naranjo, Sergio Rojas, Arturo Santos, Juan Carlos Altamirano, Yael Morales, Rhett Schiffman; Interim Results of a Dose Escalation Study of NT-503 Encapsulated Cell Therapy for the Treatment of Choroidal Neovascularization in AMD. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2277.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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