PMID- 32826769 OWN - NLM STAT- MEDLINE DCOM- 20210122 LR - 20221005 IS - 1536-481X (Electronic) IS - 1057-0829 (Print) IS - 1057-0829 (Linking) VI - 29 IP - 10 DP - 2020 Oct TI - Pooled Efficacy and Safety Profile of Netarsudil Ophthalmic Solution 0.02% in Patients With Open-angle Glaucoma or Ocular Hypertension. PG - 878-884 LID - 10.1097/IJG.0000000000001634 [doi] AB - PRECIS: In pooled phase III analyses, once-daily netarsudil 0.02% resulted in intraocular pressure (IOP) reduction that was noninferior to twice-daily timolol 0.5%, with minimal treatment-related serious or systemic adverse events (AEs). Ocular AEs were generally tolerable. PURPOSE: The purpose of this study was to assess the efficacy and safety of the Rho kinase inhibitor netarsudil in patients with open-angle glaucoma or ocular hypertension. PATIENTS AND METHODS: Pooled analysis of data from the ROCKET-1 to 4 phase III studies of once-daily (PM) netarsudil or twice-daily timolol in patients with open-angle glaucoma or ocular hypertension. The primary efficacy measure was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3 in patients with baseline IOP <25 mm Hg. RESULTS: In the pooled primary efficacy population (netarsudil, n=494; timolol, n=510), once-daily netarsudil was noninferior to twice-daily timolol at all 9 timepoints through month 3. Mean treated IOP ranged from 16.4 to 18.1 mm Hg among netarsudil-treated patients and 16.8 to 17.6 mm Hg among timolol-treated patients. In the pooled safety population (n=839 in each treatment group), treatment-related serious AEs occurred at similar frequencies in each treatment group (netarsudil, 0.1%; timolol, 0%). The most common ocular AE, conjunctival hyperemia (netarsudil, 54.4%; timolol, 10.4%), was graded as mild in 77.6% (354/456) of affected netarsudil-treated patients. CONCLUSIONS: Once-daily netarsudil resulted in IOP lowering that was noninferior to twice-daily timolol, with tolerable ocular AEs that were generally mild and self-resolving. As a first-in-class agent in the United States, with a novel mechanism of action, netarsudil may provide a useful therapeutic option for patients who would benefit from IOP lowering. FAU - Singh, Inder P AU - Singh IP AD - The Eye Centers of Racine and Kenosha, Racine, WI. FAU - Fechtner, Robert D AU - Fechtner RD AD - SUNY Upstate Medical University, Syracuse, NY. FAU - Myers, Jonathan S AU - Myers JS AD - Wills Eye Hospital, Philadelphia, PA. FAU - Kim, Terry AU - Kim T AD - Duke University School of Medicine. FAU - Usner, Dale W AU - Usner DW AD - Statistics and Data Corporation, Tempe, AZ. FAU - McKee, Hayley AU - McKee H AD - Aerie Pharmaceuticals Inc., Durham, NC. FAU - Sheng, Huan AU - Sheng H AD - Aerie Pharmaceuticals Inc., Durham, NC. FAU - Lewis, Richard A AU - Lewis RA AD - Aerie Pharmaceuticals Inc., Durham, NC. AD - Sacramento Eye Consultants, Sacramento, CA. FAU - Heah, Theresa AU - Heah T AD - Aerie Pharmaceuticals Inc., Durham, NC. FAU - Kopczynski, Casey C AU - Kopczynski CC AD - Aerie Pharmaceuticals Inc., Durham, NC. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Glaucoma JT - Journal of glaucoma JID - 9300903 RN - 0 (Antihypertensive Agents) RN - 0 (Benzoates) RN - 0 (Ophthalmic Solutions) RN - 11P2JDE17B (beta-Alanine) RN - 817W3C6175 (Timolol) RN - EC 2.7.11.1 (rho-Associated Kinases) RN - W6I5QDT7QI (netarsudil) SB - IM MH - Administration, Ophthalmic MH - Adult MH - Aged MH - Antihypertensive Agents/adverse effects/*therapeutic use MH - Benzoates/adverse effects/*therapeutic use MH - Double-Blind Method MH - Female MH - Glaucoma, Open-Angle/*drug therapy/physiopathology MH - Humans MH - Intraocular Pressure/drug effects MH - Middle Aged MH - Ocular Hypertension/drug therapy/physiopathology MH - Ophthalmic Solutions MH - Timolol/therapeutic use MH - Tonometry, Ocular MH - Treatment Outcome MH - beta-Alanine/adverse effects/*analogs & derivatives/therapeutic use MH - rho-Associated Kinases/antagonists & inhibitors PMC - PMC7647436 COIS- Disclosure: I.P.S. is a paid consultant to Aerie Pharmaceuticals and has received research funding from Aerie Pharmaceuticals, Ivantis, Glaukos, Bausch + Lomb/Valeant, Allergan, Ellex, Alcon, and Katena/IOP. He has also served as consultant to Glaukos, Bausch + Lomb/Valeant, Allergan, and Ellex and on speakers' bureaus for Glaukos, Bausch + Lomb/Valeant, Allergan, Ellex, Alcon, Katena/IOP, Shire, and Novabay. R.D.F. is a paid consultant of Aerie Pharmaceuticals and has served as a consultant to Akorn, Nicox, and Novartis. His research is supported, in part, by an unrestricted grant from Research to Prevent Blindness. J.S.M. has received honoraria from Allergan and Novartis and serves as a consultant to Aerie Pharmaceuticals, Allergan, Glaukos, MicrOptx, and Olleyes. His institution has received research grants from Aerie Pharmaceuticals, Allergan, Bausch + Lomb/Valeant, Diopsys, Heidelberg, Inotek, Merck, Novartis, Olleyes, and Zeiss. T.K. serves as a consultant to, and his institution has received research funding from, Aerie Pharmaceuticals. H.M., R.A.L., and C.C.K. are salaried employees of and own stock in Aerie Pharmaceuticals. D.W.U. is a paid statistical consultant to Aerie Pharmaceuticals. H.S. and T.H. are previous employees of Aerie Pharmaceuticals. EDAT- 2020/08/23 06:00 MHDA- 2021/01/23 06:00 PMCR- 2020/11/06 CRDT- 2020/08/23 06:00 PHST- 2020/08/23 06:00 [pubmed] PHST- 2021/01/23 06:00 [medline] PHST- 2020/08/23 06:00 [entrez] PHST- 2020/11/06 00:00 [pmc-release] AID - 00061198-202010000-00008 [pii] AID - 10.1097/IJG.0000000000001634 [doi] PST - ppublish SO - J Glaucoma. 2020 Oct;29(10):878-884. doi: 10.1097/IJG.0000000000001634.