Abstract
Purpose :
Preliminary 15-month data from an on-going Phase 1b/2 study in adolescent Stargardt Disease patients treated with Tinlarebant, an orally available retinol binding protein 4 (RBP4) antagonist, is presented.
Methods :
Thirteen subjects aged 12-18 years have been enrolled including 11 subjects rolling over from the Phase 1b portion. Subjects are receiving Tinlarebant (5 mg, p.o./day). Changes in visual function and retinal imaging parameters as well as adverse events were monitored during treatment.
Results :
At month 15 (2022/12/05), Tinlarebant continues to produce sustained RBP4 serum reduction 80-90% from baseline. Best-corrected visual acuity (BCVA) data showed 8 of 12 subjects with improvement or stabilization in at least one eye, including 3 subjects with improvement in both eyes, compared to baseline. Fundus autofluorescence (FAF) imaging data at the 12-month timepoint revealed a trend for preventing or slowing expansion of area of questionably decreased autofluorescence (QDAF) with no new atrophic lesion (definitely decreased autofluorescence, DDAF) in 12 of 13 subjects (18-month FAF data will be finalized in March 2023). Thirty-seven treatment-emergent adverse events (AEs) were reported as attributed to Tinlarebant and all were all mild in severity. Xanthopsia/chromatopsia and delayed dark adaptation (DDA) were the most frequently reported. DDA was reported by 9 of 13 subjects (69.2%), including 1 subject who recovered. Xanthopsia/chromatopsia were reported by 10 subjects (76.9%), including 6 subjects (60%) who recovered.
Conclusions :
Tinlarebant was effective to produce a sustained reduction of RBP4 during 15 months of treatment and continues to be safe and well tolerated. The reported AEs were anticipated based on the mechanism of Tinlarebant action. Preliminary efficacy data shows a trend for preventing/slowing expansion of QDAF and stabilization of visual acuity in a majority of patients after 15 months of treatment.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.