Sustained-Release Travoprost Micro-Rods Lower IOP in Beagle Dogs

Abstract

Purpose : Noncompliance with eye drop treatment is documented problem affecting as many as 50% of all glaucoma patients. Sustained-release implants have the potential to improve compliance and prevent glaucoma disease progression. LB-01 is a novel injectable micro-rod comprised of travoprost (TP) and poly-L-glutamic acid (PGA). The present study demonstrates the effectiveness of intracameral LB-01 for sustained IOP lowering in beagle dogs.

Methods : In vitro drug release testing was performed in a Slide-A-Lyzer™ device in PBS at 37°C, sampled regularly over a 2-month period and analyzed by LC-MS. IOP lowering studies were conducted in normotensive beagles in 3 groups (N=4 each) corresponding to 3 different doses of LB-01. Micro-rods were injected intracamerally in the right eye, while the left eye served as an untreated control. IOP was measured using an Icare® Tonovet tonometer, and IOP lowering was calculated as the difference between the treated eye and untreated eye. The total study study was 15 months, though individual animals were discontinued at interim time points once IOP lowering was no longer observed.

Results : In vitro release studies demonstrated zero-order release of travoprost for more than two months. In vivo IOP testing in beagles demonstrated a maximum duration of IOP lowering of 15 months for Group 1, 7 months for Group 2, and 9 months in Group 3. The mean (±SD) magnitudes of IOP lowering across all time points were 6.6 (±2.1), 8.2 (±0.6), and 7.1 (±2.6) mmHg for Groups 1, 2 and 3, respectively. The attached Figure shows the average IOP lowering over time for each group.

Conclusions : The results of this study support the therapeutic potential of LB-01 travoprost micro-rods for treatment glaucoma. A significant degree of IOP fluctuation was observed within groups and between time points for each animal, and a clear dose-response relationship was not observed. Future studies with LB-01 should employ a larger sample size and dose range to better elucidate the dose-response relationship. Use of hypertensive rather than normotensive beagles would also enhance the clinical relevance for treating actual glaucoma patients.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure. IOP Lowering in Beagle Dogs: Three doses of LB-01 travoprost micro-rods were implanted in the right eye of 12 dogs (N=4 per group) and IOP was monitored 15 months. For each time point, IOP lowering was calculated as the mean difference between the treated and untreated eye (Error bars = SEM).