Cell-Based Ciliary Neurotrophic Factor Therapy for Macular Telangiectasia Type 2.

Background: Revakinagene taroretcel (NT-501) is an encapsulated cell therapy producing ciliary neurotrophic factor that slowed retinal degeneration in patients with macular telangiectasia type 2 (MacTel) in phase 2 trials.

Methods: In NTMT-03-A and NTMT-03-B - identically designed phase 3, multicenter, randomized sham-controlled trials - we evaluated efficacy and safety of NT-501 in MacTel. The primary end point was rate of change in ellipsoid zone area (EZA) (photoreceptor) loss over 24 months (mm²/24 months). Secondary outcomes included changes in retinal sensitivity, reading speed, and National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) scores (range, 0 to 100; higher scores indicate better function). Safety end points included the proportion of participants experiencing one or more treatment-emergent serious adverse event(s) and loss of 15 or more letters in best-corrected visual acuity (BCVA). Delayed dark adaptation and miosis were among the monitored adverse events.

Results: In NTMT-03-A, adjusted rates of change of EZA loss were 0.075 mm²/24 months (95% confidence interval [CI], 0.051 to 0.099) and 0.166 mm²/24 months (95% CI, 0.141 to 0.191) in the NT-501 (n=58) and sham (n=57) groups, respectively, with a difference of -0.091 mm²/24 months (95% CI, -0.125 to -0.056; P<0.001) between groups. In NTMT-03-B, rates of EZA loss were 0.111 mm²/24 months (95% CI, 0.084 to 0.139) and 0.160 mm²/24 months (95% CI, 0.131 to 0.189) in the NT-501 (n=59) and sham (n=54) groups, respectively, with a difference of -0.049 mm²/24 months (95% CI, -0.089 to -0.008; P=0.02). Retinal sensitivity and reading-speed changes between groups were inconsistent in the trials. NEI VFQ-25 scores, BCVA loss, and treatment-emergent serious adverse events did not differ between treatment groups. Miosis was experienced by 17% and 14% of participants receiving NT-501 in NTMT-03-A and NTMT-03-B, respectively, and by none of the participants in sham groups. Delayed dark adaptation was experienced by 17% and 24% of participants receiving NT-501 in NTMT-03-A and NTMT-03-B, respectively, by none in the NTMT-03-A sham group, and by 2% in the NTMT-03-B sham group.

Conclusions: NT-501 for MacTel resulted in statistically significantly reduced EZA loss compared with sham procedures. (Funded by Neurotech Pharmaceuticals; ClinicalTrials.gov numbers, NCT03316300 and NCT03319849.).