Angiogenesis 2025: Encapsulated cell therapy for MacTel shows long-term efficacy in phase 3 trials

Martin Friedlander, MD, PhD, of the Scripps Research Institute in La Jolla, California, presented key findings on novel therapeutic approaches for macular telangiectasia type 2 (MacTel) at this year’s Angiogenesis, Exudation, and Degeneration virtual meeting held February 8, 2025. He discussed the phase 3 clinical trial of encapsulated cell therapy (ECT) (NT-501) delivering ciliary neurotrophic factor (CNTF), sponsored by Neurotech, which is currently under FDA review with a PDUFA date set for March 18, 2025.

The phase 3 trial consisted of two identical studies with approximately 120 patients each. One trial showed a 52% reduction in the progression of ellipsoid zone loss, whereas the other showed a 31% reduction, both statistically significant (P = .0001 in the stronger trial). These findings suggest the device slows photoreceptor loss, as supported by microperimetry and reading speed data, Friedlander noted. A collective analysis across phase 1, phase 2, and phase 3 trials confirmed structural and functional visual benefits.

The ECT device is a small, implantable unit containing CNTF-producing cells within a semipermeable membrane. It is sutured into the vitreous and has demonstrated long-term viability, with explanted devices still producing CNTF after 14.5 years. This innovation offers a potential alternative to frequent intravitreal injections, providing sustained neuroprotection with minimal intervention.

Friedlander also discussed the metabolic basis of MacTel, highlighting research¹ published in the New England Journal of Medicine. MacTel patients exhibit dysregulated serine and lipid metabolism. A completed study demonstrated that oral serine supplementation, with or without fenofibrate, can restore normal lipid profiles. Although its impact on visual function is still under clinical investigation, these findings support metabolic intervention as a promising therapeutic avenue. Further clinical studies are planned to evaluate visual efficacy.

Reference

1. 1. Gantner ML, Eade K, Wallace M, et al. Serine and lipid metabolism in macular disease and peripheral neuropathy. N Engl J Med. 2019;381(15):1422-1433. doi:10.1056/NEJMoa1815111