Bimatoprost Implant Biodegradation in the Phase 3, Randomized, 20-Month ARTEMIS Studies

Abstract

Purpose: To evaluate the time course of biodegradation of an intracameral, biodegradable, sustained-release bimatoprost implant that lowers intraocular pressure without the need for daily eye drops. Methods: In 2 identically designed, randomized, phase 3 clinical trials, adults with open-angle glaucoma or ocular hypertension and open iridocorneal angles inferiorly in the study eye were administered 10- or 15-μg bimatoprost implant (day 1 and weeks 16 and 32) or twice-daily topical timolol 0.5%. Implants were assessed on gonioscopy throughout the studies. Investigators reported whether implants were visible, estimated the size of visible implants relative to their initial size at implantation, and reported the implant location. Data for 10-μg implant placed on day 1 were pooled from both studies for analysis. Results: A total of 372 patients received the 10-μg bimatoprost implant. The degree of implant biodegradation at each follow-up time point was variable among patients. The implant frequently swelled during the initial phase of biodegradation from 6 to 28 weeks. Accelerated biodegradation occurred between 31 and 52 weeks, resulting in 82% of implants absent or ≤25% of initial size by 52 weeks. By month 20, 95% of implants had biodegraded to absent or ≤25% of initial size. The implant was predominantly located inferiorly in the iridocorneal angle. Conclusions: Bimatoprost implant biodegradation in phase 3 studies showed some degree of variability among patients. Clinically significant implant biodegradation was observed in the majority of patients by 12 months. Clinical studies are in progress to further understand implant biodegradation and the ideal timing for implant re-administration. ClinicalTrials.gov NCT02247804; ClinicalTrials.gov NCT02250651.

Keywords: biodegradable implant; drug delivery system; intraocular injection; prostaglandin analog; randomized clinical trial.

FIG. 1.

Zones of implant location within the iridocorneal angle. The location of each implant within 1 of 12 zones arranged circumferentially around the iridocorneal angle was determined during gonioscopic examination. OD, right eye; OS, left eye.

FIG. 2.

Distribution of implant size by time after administration. Patients were administered a 10-μg bimatoprost implant on day 1 in the ARTEMIS studies. During gonioscopic examination at follow-up visits, the size of the implant was estimated and categorized by percent initial size. Results shown are based on observed values (n = 230 at week 2).

FIG. 3.

Time course of the biodegradation of the implant. Results shown are based on observed values (n = 230 at week 2).

FIG. 4.

Implant location in the iridocorneal angle.

FIG. 5.

SEM images of representative bimatoprost implants before and 3–6 months after intracameral injection in beagle dogs. (A) Side view and (B) cross-sectional view of the rod-shaped bimatoprost implant before intracameral injection. (C) Cross-sectional view of an implant retrieved from a dog eye 3 months after injection. The implant material has become porous, indicating polymer biodegradation, and central coring is evident. (D) Side view of an implant retrieved from a dog eye 6 months after injection. The surface morphology demonstrates extensive pore formation and polymer biodegradation. SEM, scanning electron microscopy.

FIG. 6.

Gonioscopic photographs of a bimatoprost implant in the iridocorneal angle. The study eye of a patient with open-angle glaucoma was administered a single 10-μg bimatoprost implant in a phase 1/2 study.^, Gonioscopic photographs of the iridocorneal angle were taken at 2 weeks and 6, 12, and 24 months after the intracameral administration of the implant.

FIG. 7.

Schematic of bimatoprost implant biodegradation. Side view (left) and cross-sectional (right) images illustrate the initial implant (A) and the changes in implant size and structure that occur after the implant is placed in the anterior chamber (B–H).