Felipe A Medeiros1, Thomas R Walters2, Miriam Kolko3, Michael Coote4, Marina Bejanian5, Margot L Goodkin5, Qiang Guo5, Jane Zhang6, Michael R Robinson7, Robert N Weinreb8. 1. Department of Ophthalmology, Duke University, Durham, North Carolina. 2. Keystone Research, Ltd., Austin, Texas. 3. Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet-Glostrup, Glostrup, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. 4. Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia. 5. Allergan plc, Irvine, California. 6. Allergan plc, Madison, New Jersey. 7. Allergan plc, Irvine, California. Electronic address: Robinson_Michael@Allergan.com. 8. Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California, San Diego, California.
Abstract
PURPOSE: 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. DESIGN: Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: 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). RESULTS: 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. CONCLUSIONS: 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.
RCT Entities:
PURPOSE: 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. DESIGN: Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: 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). RESULTS: 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. CONCLUSIONS: 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.
Authors: Gavin W Roddy; Uttio Roy Chowdhury; Kjersten J Anderson; Tommy A Rinkoski; Cheryl R Hann; Vince A Chiodo; W Clay Smith; Michael P Fautsch Journal: PLoS One Date: 2022-05-31 Impact factor: 3.752
Authors: Kyle Battiston; Ian Parrag; Matthew Statham; Dimitra Louka; Hans Fischer; Gillian Mackey; Adam Daley; Fan Gu; Emily Baldwin; Bingqing Yang; Ben Muirhead; Emily Anne Hicks; Heather Sheardown; Leonid Kalachev; Christopher Crean; Jeffrey Edelman; J Paul Santerre; Wendy Naimark Journal: Nat Commun Date: 2021-05-17 Impact factor: 14.919
Authors: Faruque Ghanchi; Rupert Bourne; Susan M Downes; Richard Gale; Christina Rennie; Ian Tapply; Sobha Sivaprasad Journal: Eye (Lond) Date: 2022-01-01 Impact factor: 4.456
Authors: Aditya Belamkar; Alon Harris; Ryan Zukerman; Brent Siesky; Francesco Oddone; Alice Verticchio Vercellin; Thomas A Ciulla Journal: Ann Med Date: 2022-12 Impact factor: 4.709
Authors: Mark F Pyfer; Mark Gallardo; Anita Campbell; Brian E Flowers; Jaime E Dickerson; Alain Talla; Kavita Dhamdhere Journal: Clin Ophthalmol Date: 2021-09-24
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 Journal: Drugs Date: 2021-11-01 Impact factor: 9.546