Safety, Tolerability, and Efficacy of Tinlarebant from the 24-Month Phase 2 study in Adolescent Patients Affected by Stargardt Disease

Abstract

Purpose : Primary endpoint data from a 24-month, Phase 2 study in adolescent Stargardt Disease patients treated with Tinlarebant, an orally available retinol binding protein 4 (RBP4) antagonist, is presented.

Methods : Thirteen (13) clinically and molecularly confirmed STGD1 subjects aged 12-18 years showing only questionably decreased autofluorescence (QDAF) retinal lesions at baseline were treated with Tinlarebant (5 mg, p.o./day) over 24 months. Transitions to, and growth of, incident atrophic lesions identified as definitely decreased autofluorescence (DDAF) on fundus autofluorescence (FAF) photography, visual function, and adverse events were monitored during treatment.

Results : Tinlarebant produced a sustained reduction of RBP4 (80-90%) throughout the treatment period which was reversible during 28 days of drug cessation. Fundus autofluorescence imaging revealed no incident DDAF lesions in 5 of 12 subjects (42%) at Month 24 (1 subject was lost to follow-up at Month 12). For the 7 subjects with incident DDAF lesions, the change in growth at Month 24 was significantly lower (~50%) when compared to baseline matched historical controls (p<0.001). Genetic analyses showed that a majority of subjects (67%), as expected, harbored severe bi-allelic ABCA4 mutations; 62.5% of whom developed DDAF lesions after Month 12 on average. Best-corrected visual acuity was stable during the treatment period with a mean loss of 5 letters. Thirty-eight (38) drug-related treatment-emergent adverse events (AEs) were reported; all were mild in severity. Incidences of xanthopsia/chromatopsia (10 of 13 subjects [76.9%]) and delayed dark adaptation (9 of 13 subjects [69.2%]) were most frequently reported.

Conclusions : Tinlarebant produced a sustained and reversible reduction of RBP4 during 24 months of treatment and was found to be safe and well tolerated. The reported ocular AEs were anticipated based on the mechanism of Tinlarebant action. The absence of transition from QDAF lesions to atrophic lesions in 5 of 12 subjects over 24 months of Tinlarebant treatment, and the significantly reduced growth of incident atrophic lesions, is encouraging for the future development of Tinlarebant.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.