Phase 3, Randomized, 20-Month Study of Bimatoprost Implant in Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 1)
Authors: Felipe A. Medeiros, Thomas R. Walters, Miriam Kolko, Michael Coote, Marina Bejanian, Margot L. Goodkin, Qiang Guo, Jane Zhang, Michael R. Robinson, Robert N. Weinreb, Ashish Agar, Michael Coote, Renuka Bathijia, Lance Liu, Tim Roberts, Christoph Faschinger, Clemens Vass, Nathalie Collignon, Ana Claudia Alves Pereira, Rubens Belfort de Mattos, Fernando Justino Dantas, Marcelo Jordao Lopes da Silva, Fabio Kanadani, Leopoldo Magacho dos Santos Silva, Tiago Prata, Daniella Bach-Holm, Miriam Kolko, Jimmy Lai, Clement Tham, György Bátor, Lajos Szalczer, Balázs Varsányi, Eytan Blumenthal, Orna Geyer, Shmuel Lavartovsky, Tamar Pedut-Kloizman, Nir Shoham-Hazon, Silvio Lujan, Benjamin Abela, Robert E. Ang, Edgar U. Leuenberger, Harvey Uy, Maria Imelda Yap-Veloso, Piotr Fryczkowski, Piotr Jurowski, Bartlomiej Kalużny, Józef Kalużny, Marta Misiuk-Hojlo, Krystyna Raczynska, Wioletta Tomczyk-Dorozynska, Jaromir Wasyluk, Slawomir Zalewski, Tomasz Zarnowski, Julian Garcia Feijoó, Rafael Giménez-Gómez, Elena Milla Griño, Alfonso Antón López, Merce Guarro Miralles, Javier Montero Moreno, Vicente Polo, Enrique Cervera Taulet, Beatriz Ponte Zúñiga, Ying-Ying Chen, Yuan-Chieh Lee, Louis Alpern, Michael S. Berlin, Jacob Brubaker, Delmar Caldwell, Andrew Camp, Louis B. Cantor, Ronald Caronia, Charles J. Crane, Douglas Day, Eran Duzman, John Elfervig, Sherif El-Harazi, Richard Evans, Ann C. Fisher, William John Flynn, Charles Stephen Foster, Ronald Frenkel, Raj Goyal, Ronald Gross, Paul J. Hartman, William L. Haynes, Gary Jerkins, Janet Kim, Max Kim, Bradley Kwapiszeski, Benjamin Lambright, Christine Larsen, James Lehmann, Jeffrey H. Levenson, Dwayne Logan, Brian McMillan, Joseph R. Martel, Hylton Mayer, Felipe Medeiros, Sayoko Moroi, Andrew Moyes, Jonathan Myers, John Nairn, Steven Nielsen, Don Perez Ortiz, James Paauw, Vicky Pai, Joseph Panarelli, Abraham Park, Mujtaba A. Qazi, Nikola Ragusa, Douglas J. Rhee, Robert Rothman, Reginald Sampson, Samuel Seltzer, Anurag Shrivastava, Steven T. Simmons, Annette Sims, Mark A. Slabaugh, Scott Smetana, Oluwatosin Smith, Scott C. So, Ingeborg Stalmans, Jitendra Swarup, Jay Wallshein, Thomas R. Walters, Fiaz Zaman, Rui Zhang
Journal: Ophthalmology (2020)

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations.Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study.Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout.Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit.Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD).Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit.Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.