First-Ever Treatment for Rare Eye Disease Wins FDA Approval After Landmark Trials

Phase 3 clinical trial results from Scripps Research and its collaborators supported FDA approval of ENCELTO, the first cell-based treatment for the neurodegenerative retinal disease known as MacTel.

For individuals with macular telangiectasia type 2 (MacTel), a rare retinal disease that steadily erodes central vision, no approved therapies had previously existed. Now, a study led by investigators at Scripps Research and the National Institutes of Health (NIH), and sponsored by Neurotech Pharmaceuticals, provides strong evidence that a neuroprotective surgical implant can slow the progression of vision loss.

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

The research, published in NEJM Evidence on July 22, 2025, presents findings from two phase 3 clinical trials of ENCELTO (revakinagene taroretcel-lwey), an implanted device that steadily releases a therapeutic protein to help maintain vision. The trials, conducted over 24 months at 47 sites worldwide, enrolled 228 people with MacTel.

Coordinated through a global collaboration of clinicians and scientists, with contributions from the NIH’s National Eye Institute, the Lowy Medical Research Institute, and Neurotech Pharmaceuticals, the trials provided the critical data that supported the US Food and Drug Administration’s March 2025 approval of ENCELTO. This decision marked the first approved therapy for MacTel and the first cell-based neuroprotective treatment for any neurodegenerative retinal or central nervous system disease.

Consistent preservation of vision across trials

The two trials were designed in the same way but involved participants recruited at different times and locations. Both demonstrated that ENCELTO slowed the decline of light-sensing retinal cells, though one trial showed a stronger effect, likely reflecting differences in disease severity and other variables among participants. Taken together, the findings strongly support the implant’s ability to help preserve vision in individuals with MacTel.

“This is the first time we’ve seen a therapy meaningfully alter the course of MacTel,” says Friedlander. “It confirms that neuroprotection can be a powerful strategy to preserve vision in degenerative retinal conditions.”

Friedlander, who also serves as president of the Lowy Medical Research Institute, has studied MacTel for nearly 20 years and helped build the scientific foundation for ENCELTO. The implant delivers ciliary neurotrophic factor (CNTF), a natural protein known to protect retinal neurons. It consists of genetically engineered retinal pigment epithelial cells, which provide essential support to the retina, enclosed in a small collagen-based capsule implanted at the back of the eye. This capsule shields the cells from immune attack while allowing them to release CNTF continuously, enabling long-term, localized treatment.

Significant reduction in photoreceptor loss

The research showed that ENCELTO substantially slowed the degeneration of photoreceptors—light-detecting nerve cells essential for central vision—compared with sham-treated eyes that underwent a simulated surgery without receiving the implant. In one trial, the implant reduced the rate of ellipsoid zone loss, a marker of photoreceptor damage, by 54.8%. The second trial demonstrated a 30.6% reduction, smaller in magnitude but still statistically significant.

Beyond structural changes, the study assessed multiple measures of visual function, including microperimetry (a sensitive test of retinal light response) and reading speed. Microperimetry results indicated a clear slowing of functional decline, especially in the trial that showed stronger photoreceptor preservation. However, outcomes for reading speed and retinal sensitivity were mixed, with one trial showing improvement while the other found no significant difference compared with controls.

“These differences highlight just how complex it is to measure functional vision loss in a slow-progressing disease like MacTel,” points out Friedlander. “If you look at certain functional outcomes from just one of the trials, they’re not statistically significant. But when you pool data from both trials—which were conducted the same way—then you see statistically significant results, so we’ll continue to investigate what’s driving that.”

Benefits with early intervention

Despite the variability, the overall trend across both trials supports ENCELTO’s long-term benefit, particularly when treatment is initiated before extensive cell loss. Participants tolerated the implant well, with minimal side effects. Furthermore, ENCELTO was effective regardless of the participant’s baseline vision or disease stage, suggesting that earlier intervention may help preserve more functional vision as MacTel progresses.

Next, Friedlander and his team will assess whether benefits continue or even improve beyond 24 months. There are also plans to explore why some individuals experienced greater gains than others, which may help identify patient subgroups that are most likely to benefit.

“The consistency in preserving retinal cells across both trials gives us confidence in the mechanism,” says Friedlander. “As we refine how and when to treat MacTel, we expect even greater improvements in vision over time.”

Moreover, because ENCELTO delivers sustained, targeted doses of therapeutic proteins directly to the retina, it represents a versatile platform technology. This same approach could potentially be adapted to treat a wide range of neurovascular degenerative diseases beyond MacTel, including other blinding conditions where protecting vulnerable nerve cells is key.

Reference: “Cell-Based Ciliary Neurotrophic Factor Therapy for Macular Telangiectasia Type 2” by Emily Y. Chew, Mark Gillies, Glenn J. Jaffe, Alain Gaudric, Cathy Egan, Ian Constable, Traci Clemons, Thomas Aaberg Jr., Debora C. Manning, Thomas C. Hohman, Alan Bird, Martin Friedlander and for the MacTel CNTF NTMT-03 Research investigators, 22 July 2025, NEJM Evidence.
DOI: 10.1056/evidoa2400481

This work was supported by funding from Neurotech Pharmaceuticals, Inc.

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