Fingeret Murray, Gaddie Ian B, Bloomenstein Marc
VA New York Harbor Health Care System, Brooklyn and St. Albans Campus, Queens, New York, USA.
Gaddie Eye Centers, Louisville, Kentucky, USA.
Clin Exp Optom. 2019 Nov;102(6):541-550. doi: 10.1111/cxo.12853. Epub 2019 Jan 7.
Latanoprostene bunod (LBN) ophthalmic solution 0.024% is a novel, once-daily, nitric oxide-donating prostaglandin analogue for the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. The IOP-lowering actions of LBN are mediated by dual mechanisms of the molecule for increasing aqueous humour outflow. The prostaglandin analogue moiety (latanoprost acid) increases uveoscleral outflow, whereas nitric oxide, released by the nitric oxide-donating moiety (butanediol mononitrate), increases outflow through the trabecular meshwork and the Schlemm's canal. The clinical efficacy and safety of LBN 0.024% in patients with open-angle glaucoma or ocular hypertension were established in two similarly designed, double-masked, pivotal phase 3 studies, APOLLO and LUNAR, the pooled three-month efficacy phase of which demonstrated significantly greater IOP-lowering of once-daily LBN 0.024% over twice-daily timolol 0.5% at all time points. Additional support for the IOP-lowering effects of LBN 0.024% was provided by two phase 2 studies in patients with open-angle glaucoma or ocular hypertension (a dose ranging study versus latanoprost and a 24-hour IOP crossover study versus timolol) and a phase 1 study of healthy volunteers with IOP in the normal range. In addition, long-term efficacy and safety were demonstrated in the open-label safety-extension phases of the phase 3 pivotal studies and a phase 3 52-week open-label study of patients with open-angle glaucoma (including normal-tension glaucoma) or ocular hypertension. In conclusion, LBN 0.024% has demonstrated both short-term and long-term IOP-lowering efficacy in patients with open-angle glaucoma or ocular hypertension, including in healthy volunteers and patients with IOP in the normal range, without apparent clinically-limiting safety or tolerability concerns.
0.024%的拉坦前列素倍诺德（LBN）滴眼液是一种新型的、每日一次的、可释放一氧化氮的前列腺素类似物，用于降低开角型青光眼和高眼压症患者的眼压（IOP）。LBN降低眼压的作用是通过该分子增加房水流出的双重机制介导的。前列腺素类似物部分（拉坦前列酸）增加葡萄膜巩膜流出，而由一氧化氮供体部分（丁二醇单硝酸酯）释放的一氧化氮增加通过小梁网和施莱姆管的流出。在两项设计相似、双盲、关键的3期研究APOLLO和LUNAR中确定了0.024%的LBN在开角型青光眼或高眼压症患者中的临床疗效和安全性，这两项研究的合并三个月疗效阶段表明，在所有时间点，每日一次的0.024%LBN比每日两次的0.5%噻吗洛尔显著降低更多眼压。两项针对开角型青光眼或高眼压症患者的2期研究（一项与拉坦前列素的剂量范围研究和一项与噻吗洛尔的24小时眼压交叉研究）以及一项针对眼压在正常范围内的健康志愿者的1期研究，为0.024%的LBN降低眼压的作用提供了额外支持。此外，在3期关键研究的开放标签安全性扩展阶段以及一项针对开角型青光眼（包括正常眼压性青光眼）或高眼压症患者的3期52周开放标签研究中证明了长期疗效和安全性。总之，0.024%的LBN在开角型青光眼或高眼压症患者中已证明具有短期和长期降低眼压的疗效，包括在健康志愿者和眼压在正常范围内的患者中，且没有明显的临床限制安全性或耐受性问题。
