Oral delivery of the anti-fibrotic, FT011, achieves safe and robust intraocular levels of exposure in subjects undergoing glaucoma filtration surgery

Abstract

Purpose : Despite modern modifications in surgical technique, serious limitations still exist in wound healing management following glaucoma filtration surgery (GFS). FT011 is a novel oral anti-fibrotic small molecule compound that has previously demonstrated superior anti-fibrotic and anti-inflammatory properties in various in vitro and in vivo models. This study tested the hypothesis that oral delivery of FT011 leads to safe and adequate exposure levels in ocular tissues that may ultimately improve the wound healing process following GFS and improve surgical safety and efficacy.

Methods : Eight patients who were scheduled to undergo GFS at the Royal Victorian Eye and Ear Hospital were recruited. Patients in cohort 1 and 2 were randomised to receive 50 or 100 mg of FT011, respectively, or placebo in a 3:1 ratio. Drug was taken once daily for 28 days starting one week before surgery (Day 0). Physical and ophthalmic examinations were performed on Day 0, Day 7 (before surgery), and at Week 4 and 12. Plasma was collected before surgery and at Week 4 to confirm systemic exposure of FT011. Aqueous humor (AH) and a biopsy of Tenons’ capsule (TC) was collected during surgery to determine the ocular exposure of FT011. The concentration of FT011 in tissue samples was measured using a precipitation extraction procedure followed by HPLC with MS/MS detection.

Results : FT011 was detected in AH in all patients taking the study drug. The maximum concentrations observed were 4.83 and 40.3 ng/mL at 3.5 and 4.83 hours post-dose for the 50 and 100 mg cohorts, respectively, indicating there may be a higher than dose-proportional increase of FT011 exposure in AH. FT011 was detected in 4 out of 6 TC biopsies from patients taking study drug; 2 biopsies had insufficient tissue mass to detect FT011. Exposure levels in TC were higher than AH with maximum concentrations of 780 and 33,800 ng/g at 1.5 and 3.58 hours post-dose for the 50 and 100 mg cohorts, respectively. After 4 weeks of dosing, there were no FT011-related adverse reactions and drug tolerance was high.

Conclusions : Oral delivery of FT011 achieved safe and robust exposure levels in AH and TC and 28 days of dosing was well-tolerated. A follow up study is required to determine if FT011 improves the safety and efficacy of GFS by improving the wound healing process over standard of care.

This is a 2020 ARVO Annual Meeting abstract.