Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)
Authors: Jason Bacharach, Andrew Tatham, Gloria Ferguson, Sandra Belalcázar, Hagen Thieme, Margot L. Goodkin, Michelle Y. Chen, Qiang Guo, Jeen Liu, Michael R. Robinson, Marina Bejanian, David L. Wirta, Arturo Alezzandrini, Gabriel Bercovich, Pablo Deromedis, Federico Furno Sola, Carolina Gentile, Simon Lerner, Anahi Lupinacci, Carlos Zeolite, Catherine Birt, Andrew Crichton, Sebastien Gagne, Michael Giunta, Paul Harasymowycz, Delan Jinapriya, Marcelo Nicolela, Donald Nixon, Patrick Saurel, David Yan, Darana Yuen, Santiago Arango, Sandra Belalcázar, Alexander Martinez, Juan Camilo Parra Restrepo, Vladimir Korda, Jana Kadlecova, Jitka Svacinova, Hany Khairy, Hani El Ibiary, Zeinab El Sanabary, Katharina Bell, Roman Greslechner, Jöerg Koch, Katrin Lorenz, Isabel Oberacher-Velten, Stefanie Schmickler, Claudie Schuart, Hagen Thieme, Francesco Bandello, Carlos Cagini, Michele Figus, Leonardo Mastropasqua, Luca Rossetti, Maurizio Giacinto Uva, Sandragasu Thayanithi, Anthony Wells, Rahat Husain, Victor Koh, Dawn Lim, Aung Tin, Petrus Gous, Lynette Venter, Changwon Kee, Michael Kook, Ki-Ho Park, Muhsin Eraslan, Ozcan Kayikcioglu, Nilgun Yildirim, Rupert Bourne, Anshoo Choudhary, Francesca Cordeiro, Vincent Dubois, James Kirwan, Sheng Lim, Keith Martin, Antony Nithy, Avinash Prabhu, Andrew Tatham, Ahmad Amir, Jason Bacharach, Howard Barnebey, Allen Beck, Lance Bergstrom, Navaneet Borisuth, James D. Branch, Jonathan Briggs, Stephen Bylsma, Peter Chang, William Christie, Frank Cotter, Michael Depenbusch, Damien F. Goldberg, Jack Greiner, Shailesh Gupta, Ron Gutmark, Ying Han, Sebastian Heersink, Malik Kahook, Albert Khouri, Joshua Kim, Howard Kushnick, Christopher Lin, Jodi Luchs, Arindel Maharaj, Steven L. Mansberger, Frank Mares, Eydie Miller-Ellis, Satish Modi, Matthew Paul, Ian Pitha, Robert Saltzmann, Michelle Sato, Michael Savestsky, Bruce Segal, Zachary Segal, Janet Serle, Mark Sherwood, Inder Singh, Stephen E. Smith, Julia Song, Robert Sorenson, Lawrence Tenkman, Navin Tekwani, Carl Tubbs, Farrell Tyson, Gianmarco Vizzeri, Steven Vold, Qui Vu, Kimberly S. Warren, David Wirta
Journal: Drugs (2021)

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma. NCT02250651.