Single Administration of Intracameral Bimatoprost Implant 10 µg in Patients with Open-Angle Glaucoma or Ocular Hypertension

Abstract

Introduction: This study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension.

Methods: Two identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 study datasets evaluated outcomes in the 10-µg bimatoprost implant and comparator treatment arms after a single implant administration, up to the time of implant re-administration or rescue with IOP-lowering medication.

Results: In the phase 3 studies, 10-µg bimatoprost implant single administration demonstrated IOP reductions (hour 0) of 4.9-7.0 mmHg through week 15 from a mean (standard deviation, SD) baseline IOP of 24.5 (2.6) mmHg (n = 374); IOP in the topical timolol BID group was reduced by 6.0-6.3 mmHg from a mean (SD) baseline IOP of 24.5 (2.6) mmHg (n = 373). In the phase 1/2 study (n = 21), median time to use of additional IOP-lowering treatment (Kaplan-Meier analysis) was 273 days (approximately 9 months), and 5 of 21 enrolled patients (23.8%) required no additional IOP-lowering treatment up to 24 months after single administration. In each study, after a single implant administration there were no reports of corneal edema, corneal endothelial cell loss, or corneal touch, and no patients had 20% or greater loss in corneal endothelial cell density.

Conclusions: Bimatoprost implant single administration lowers IOP and has a favorable safety profile. Additional studies are needed to further evaluate the duration of effect and factors predicting long-term IOP lowering after a single implant administration.

Trial registration numbers: ClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364.

Keywords: Adherence; Drug delivery system; Drug implant; Glaucoma; Prostaglandin analog.

© 2022. The Author(s).

Figures

Fig. 1

IOP in study eyes after a single administration of 10-µg bimatoprost implant or topical timolol maleate 0.5% BID through week 15 in the pooled ARTEMIS phase 3 studies. The analysis used observed values for eyes that had not received any rescue IOP-lowering treatment. a Mean ± SD IOP. b Postbaseline IOP was compared between groups at hours 0 and 2 at weeks 2, 6, 12, and 15 using a mixed-effects model for repeated measures. Least-squares estimates of mean ± SE IOP at postbaseline time points, the differences between groups (bimatoprost implant minus timolol), and the 95% CIs of the between-group differences were derived from the model. Baseline IOP is mean ± SE calculated in a separate analysis. BID twice daily, CI confidence interval, IOP intraocular pressure, SD standard deviation, SE standard error

Fig. 2

Responder rates for a 10-µg bimatoprost implant vs topical timolol maleate 0.5% BID in the pooled ARTEMIS phase 3 studies and b 10-µg bimatoprost implant vs topical bimatoprost 0.03% QD in the phase 1/2 study. BID twice daily, IOP intraocular pressure, QD once daily

Fig. 3

IOP in non-rescued eyes after a single administration of 10-µg bimatoprost implant or once-daily topical bimatoprost 0.03% through month 24 in the phase 1/2 study. The analysis used observed values for eyes that had not received any rescue IOP-lowering treatment or a second administration of implant. Values shows are mean ± SD. The differences between groups (study eye minus fellow eye) and 95% CIs of the differences were calculated using paired t tests. CI confidence interval, H hour, IOP intraocular pressure, SD standard deviation

Fig. 4

Kaplan–Meier survival analysis of time to initial use of any additional IOP-lowering treatment (rescue topical medication or a second administration of implant) after a single administration of bimatoprost implant 10 µg on day 1 in the phase 1/2 study. The estimated median time to use of additional IOP-lowering treatment was 273 days. At 720 days, the number of patients at risk was 3 rather than 5, because 2 patients had already completed the study without rescue or re-treatment. IOP intraocular pressure

Fig. 5

Proportion of study eyes with loss in CECD from baseline to week 12 after administration of a 10-µg bimatoprost implant or beginning topical timolol BID treatment on day 1 in the pooled ARTEMIS phase 3 studies. BID twice daily, CECD central corneal endothelial cell density

Fig. 6

Mean ± SD CECD at baseline and during treatment in the phase 1/2 study. Study eyes received a single administration of bimatoprost implant 10 µg, and fellow eyes were treated with topical bimatoprost 0.03% QD. Eyes were censored from the analysis at the time of implant re-treatment but could have received topical rescue IOP-lowering medication and remained in the analysis. The differences between groups (study eye minus fellow eye) and 95% CIs of the differences were calculated using paired t tests. BL baseline, CECD central corneal endothelial cell density, CI confidence interval, IOP intraocular pressure, M month, QD once daily, SD standard deviation, W week