Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration. American journal of ophthalmology Rakoczy, E. P., Magno, A. L., Lai, C., Pierce, C. M., Degli-Esposti, M. A., Blumenkranz, M. S., Constable, I. J. 2019; 204: 113–23

Abstract

PURPOSE: To assess the safety and the 3-year results of combined phase 1 and 2a randomized controlled trials of rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration.DESIGN: Phase 1/2a clinical trial.METHODS: Patients were prospectively randomized into control (n= 13) and GT (n= 24) groups. GT patients received 1X1011vg rAAV.sFLT-1 and were seen every month for 1 year then as needed every 1 to 2months. They were given retreatment anti-vascular endothelial growth factor injections according to predetermined criteria. At 12months, GT patients were divided into 2 groups: HD-1 (n= 14), requiring <2, and HD-2 (n= 10), requiring >2 retreatments.RESULTS: Between 1 year and 3 years there were 3 adverse events (AEs) and 33 serious AEs reported. Of these, 15 occurred in the 13 control subjects and 21 in the 24 GT patients. Except for 1 case of transient choroiditis in a control patient, serious AEs were deemed to be unrelated to the study. Control patients received a median of 7.0 retreatments and lost a median of 7.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, HD-1 patients received a median of 2.5 retreatments and lost a median of 4.0 ETDRS letters, and HD-2 patients received a median of 11.0 retreatments and lost a median of 7.0 ETDRS letters over 3 years. Center point thickness fluctuated. Thirty-three percent of control subjects, 44% of HD-2 patients, and 51% of HD-1 patients showed maintenance of baseline visual acuity. Four HD-1 patients (34%) maintained significant visual improvement at 3 years. None of these observations were statistically significant.CONCLUSIONS: Given the small number of patients, this study was unable to unequivocally confirm the existence of a biologic efficacy signal; however, it confirmed that rAAV.sFLT-1 gene delivery was well tolerated among the elderly.

View details for DOI 10.1016/j.ajo.2019.03.006

View details for PubMedID 30878487