ENCELTO Implant Slows Vision Loss in MacTel

For individuals with macular telangiectasia type 2 (MacTel), a rare, progressive retinal disorder that gradually destroys central vision, there have historically been no approved treatment options. Now, results from a landmark study sponsored by Neurotech Pharmaceuticals and led by investigators at Scripps Research and the National Institutes of Health (NIH) offer compelling evidence that vision loss can be slowed with a neuroprotective surgical implant.

“This is a step toward redefining how we think about vision loss,” said Professor Martin Friedlander of Scripps Research. “Instead of waiting for cells to die, we’re learning how to protect and preserve them.”

Phase III Trials Validate ENCELTO’s Effectiveness

The study, published in NEJM Evidence, reports findings from two Phase III clinical trials evaluating ENCELTO (revakinagene taroretcel-lwey), a surgically implanted device that continuously releases a therapeutic protein to preserve vision.

Conducted across 47 international sites, the randomized trials enrolled 228 participants with MacTel and tracked their progress over 24 months. Coordinated by a global network of clinicians and researchers, with collaboration from the NIH’s National Eye Institute, the Lowy Medical Research Institute, and Neurotech Pharmaceuticals, the trials helped support FDA approval of ENCELTO in March 2025. This milestone made ENCELTO the first approved treatment for MacTel and the first cell-based neuroprotective therapy for any neurodegenerative retinal or central nervous system disease.

Mechanism of Action: Continuous Neuroprotection

ENCELTO delivers ciliary neurotrophic factor (CNTF), a naturally occurring protein that protects retinal neurons, using genetically modified retinal pigment epithelial cells housed in a tiny, collagen-based capsule implanted at the back of the eye.

This capsule design shields the cells from immune rejection while allowing continuous, localized CNTF release, ensuring long-term neuroprotection and preservation of retinal function.

Key Outcomes from the Trials

Both trials confirmed that ENCELTO slows the loss of light-sensing photoreceptor cells, which are crucial for central vision.

• Trial 1: 54.8% reduction in the rate of ellipsoid zone loss, a structural measure of photoreceptor degeneration.

• Trial 2: 30.6% reduction in the same measure, also statistically significant but less pronounced, likely due to differences in disease severity and participant characteristics.

Visual function assessments included microperimetry and reading speed tests. Microperimetry showed statistically significant slowing of vision loss, particularly in the trial with greater photoreceptor preservation. Reading speed and retinal sensitivity outcomes were mixed, one trial demonstrated improvement, while the other showed no significant difference from controls.

“These differences highlight the complexity of measuring functional vision in a slow-progressing disease like MacTel,” Friedlander noted. “When pooling data from both trials, the results reach statistical significance, and we’ll continue to explore what drives these variations.”

Safety and Patient Benefit

Participants tolerated ENCELTO well, with minimal side effects. The implant was effective regardless of baseline vision or disease stage, suggesting that earlier intervention could preserve more functional vision as the disease progresses.

The trials also suggest that initiating treatment before extensive cell loss maximizes long-term benefits.

Next Steps and Broader Potential

Researchers will now investigate whether benefits continue or improve beyond the 24-month study period and aim to understand why some patients experience greater improvements than others.

“The consistency in preserving retinal cells across both trials gives us confidence in the mechanism,” said Friedlander. “As we refine treatment timing, we expect even greater improvements in vision over time.”

Reference:

Emily Y. Chew et al, Cell-Based Ciliary Neurotrophic Factor Therapy for Macular Telangiectasia Type 2, NEJM Evidence (2025). DOI: 10.1056/EVIDoa2400481