Abstract
Purpose :
Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy and usually leads to debilitating vision loss. In preclinical studies, a small, azobenzene, photoswitch molecule (BENAQ) directly rendered retinal ganglion cells light sensitive. This compound was developed for human intravitreal delivery (KIO-301). The ABACUS-1 study investigated KIO-301 for safety and activity in a first-in-human, phase 1/2, open-label, dose-escalation trial in blind individuals with advanced RP (NCT05282953).
Methods :
The study enrolled 12 eyes of 6 participants with visual acuity (VA) ranging from "count fingers" (CF) to no light perception (NLP). Participants received a single intravitreal injection sequentially to each eye in doses ranging from 7.5 μg to 50 μg and were followed longitudinally for 4 weeks after injection to each eye. The primary endpoint was safety and tolerability. Secondary endpoints included functional visual assessments, mobility testing, functional magnetic resonance imaging (fMRI) and participant-reported outcomes, including the NEI VFQ-25.
Results :
All participants completed the study. The only adverse event (AE) deemed possibly drug related was mild ocular hypertension in one participant post injection. There was no intraocular inflammation at any time point. A concordant trend of improvement in light perception, VA, and field of vision was observed. In addition, there were trended improvements in multiple assessments of functional vision, including a mobility and orientation test, increasing from 25% success at baseline to 65% success at day 14 (n = 10 eyes, 6 participants). fMRI showed a clear increase in primary (area V1) and extra-striate visual cortex activity. Participant-reported quality of life also improved. One participant with NLP at baseline recovered light perception with projection by day 7.
Conclusions :
KIO-301 displayed an excellent safety profile in this phase 1/2 clinical trial. The concordance of subjective and objective efficacy signals and positive participant-reported experiences demonstrate a proof-of-concept for vision restoration with KIO-301 and motivate a larger, randomized, controlled trial of this novel, gene-agnostic small molecule therapy for advanced RP and potentially other inherited retinal diseases.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.