Tolerability evaluation of RTC-620, a surface eroding bimatoprost acid prodrug intravitreal implant developed for long-term intraocular pressure control

Abstract

Purpose : There is a significant unmet need for safe, sustained drug release strategies to address poor compliance with topical formulations for management of primary open angle glaucoma (POAG) or ocular hypertension (OHT). The intravitreal (IVT) route of administration for sustained drug release implants has the potential to provide therapeutic benefit to patients while avoiding corneal toxicity issues associated with commercial intracameral alternatives. The purpose of this study was to assess the duration of drug release and ocular safety profile following administration of RTC-620 IVT Implants to support their further evaluation for management of intraocular pressure (IOP) in patients with POAG or OHT.

Methods : RTC-620 IVT Implants were prepared by melt extrusion of RTC-620 without inclusion of polymers or fillers, such that the implants consisted entirely of the RTC-620 prodrug processed into implant form. Tolerability was assessed following IVT administration of RTC-620 IVT Implants (low dose – 115 µg, high dose – 275 µg) in New Zealand white rabbits (3 rabbits/6 eyes per group). Ocular assessments were performed at days 3, 7, 14, 28, and every 28 days thereafter, until day 168, by slit lamp examination, fundus imaging, and optical coherence tomography (OCT).

Results : RTC-620 IVT Implants were well tolerated with no adverse events noted acutely following implantation or following chronic exposure up to day 168, as assessed by slit lamp examination, fundus imaging, and OCT. Fundus imaging visualized the implants up to Day 168. Since RTC-620 IVT Implants consist entirely of the RTC-620 prodrug, this data confirms a duration of drug release of at least 6 months with both the low and high dose implants (Figure 1).

Conclusions : RTC-620 IVT implants exhibited a favorable tolerability profile following IVT administration of the prostaglandin prodrug implants. Fundus imaging demonstrates implant persistence >6 mo, suggesting the potential for RTC-620 IVT Implants to provide long-term IOP control with a strong safety profile. Ongoing work is assessing the levels of bimatoprost acid detected in ocular tissues following RTC-620 IVT Implantation in NZW rabbits. Furthermore, a canine pharmacodynamics study is planned to assess their IOP-lowering effect.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Fundus micrographs of RTC-620 IVT implants post-implantation in the vitreous humor.