Long-Term Durability of Ciliary Neurotrophic Factor-Releasing Revakinagene Taroretcel-lwey in Individuals With Retinal Degenerative Disorders.

PURPOSE: This retrospective analysis examined drug release levels and long-term function of revakinagene taroretcel-lwey (formerly known as NT-501), a ciliary neurotrophic factor (CNTF)‒releasing encapsulated cell therapy, following implant durations of 0.5 to 14.5 years in participants with retinal degenerative disease. METHODS: Explant samples were collected from participants in 6 clinical trials (NCT00063765, NCT00447993, NCT00447980, NCT01530659, NCT03319849, and NCT00447954) and assessed for release rate of CNTF, histomorphology of encapsulated cells, and CNTF integrity and activity. Serum samples were tested for CNTF levels as well as antibodies to CNTF and the CNTF-producing NTC-201-6A cells. RESULTS: A total of 49 explanted revakinagene taroretcel-lwey devices were analyzed. Analyses showed that they produced steady levels of bioactive CNTF over a duration of 14.5 years. The weighted mean rate of CNTF produced averaged 1.6 ng/day (95% confidence interval; [CI] = 1.388 to 1.840), a rate shown to be effective in slowing photoreceptor loss. Potency of secreted CNTF was tested from a subset of explants and showed that CNTF from explanted devices remained equally bioactive compared with a CNTF reference standard. Explanted devices produced CNTF glycoforms at the expected molecular weights. Histological evaluation comparing preimplant cells to those explanted over 14.5 years revealed cells were similar in distribution and morphology. There was no evidence of an immunological reaction to CNTF or the NTC-201-6A cells. CONCLUSIONS: This retrospective analysis suggests that a single, intraocular administration of revakinagene taroretcel-lwey provides sustained, bioactive CNTF for durations exceeding a decade, potentially providing a long-term treatment option for chronic retinal degenerative diseases.