Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension

Abstract

Purpose: A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication.

Methods: Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1-2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters.

Results: Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months.

Conclusion: The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months.

Trial registry: ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.

Fig. 1

Travoprost intraocular implant inserter system. A safety clip holds the release button in the forward position during shipping, storage, and handling, thus preventing the premature release of the implant. The magnified view shows the inserter tip with grasper and a released implant (a). Anchored location of the travoprost intraocular implant in the anterior chamber angle of the eye (b)

Fig. 2

Mean 8:00 AM IOP change from baseline in the travoprost intraocular implant (FE implant and SE implant) and topical timolol 0.5% BID groups through month 36. IOP change from baseline was calculated using the unweighted average of the treatment group mean change from baseline from day 10 to the indicated visit. IOP change from baseline was statistically significant (P < 0.0001; one-sample t tests) at all visits for all treatment groups. BID twice daily, FE Implant fast-eluting travoprost intraocular implant, IOP intraocular pressure, SE Implant slow-eluting travoprost intraocular implant

Fig. 3

Percentage of study eyes in the travoprost intraocular implant (FE implant and SE implant) and timolol groups at month 12, month 24, and month 36 with well-controlled IOP (i.e., those not requiring additional IOP-lowering medication per the protocol mandated criterion) while on the same or lesser number of topical IOP-lowering medications as at screening. *P ≤ 0.0026 versus timolol, ^‡P < 0.10 versus timolol based on Pearson chi-squared test. BID twice daily, FE Implant fast-eluting travoprost intraocular implant, IOP intraocular pressure, SE Implant slow-eluting travoprost intraocular implant

Fig. 4

Mean IOP reductions in the subgroups of study eyes in the travoprost intraocular implant (FE and SE) and timolol groups at month 12, month 24, and month 36 with well-controlled IOP while on the same or lesser number of topical IOP-lowering medications as at screening. *P < 0.0001 for change from baseline in IOP based on one-sample t test. BID twice daily, FE Implant fast-eluting travoprost intraocular implant, IOP intraocular pressure, SE Implant slow-eluting travoprost intraocular implant

Fig. 5

Mean central corneal endothelial cell counts over time in study eyes treated with travoprost intraocular implant (FE implant or SE implant) or twice-daily (BID) topical timolol 0.5%. At month 36, the difference in change from baseline in corneal endothelial cell counts between the FE implant and timolol groups was −37.9 cells/mm² (two-sample t test, P = 0.1730, 95% CI: − 92.9, 17.0) and between the SE implant and timolol groups was − 18.3 cells/mm² (two-sample t test, P = 0.4581, 95% CI: − 67.2, 30.6). Error bars indicate the standard deviation. BID twice daily, CI confidence interval, FE Implant fast-eluting travoprost intraocular implant, SE Implant slow-eluting travoprost intraocular implant