Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study

Medeiros, Felipe A.; Martin, Keith R; Peace, James; Sforzolini, Baldo Scassellati; Vittitow, Jason L; Weinreb, Robert N.

doi:10.1016/j.ajo.2016.05.012

Cited by 90 publications

(90 citation statements)

References 39 publications

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“…This radical affects an early step in the replication cycle of influenza viruses and NO has been shown to severely impair the replication of influenza A and B viruses 11. In the outflow physiology, NO has been reported to contribute to the physiological regulation of aqueous humor outflow and to lower intraocular pressure in various animal models and human patients 5, 12, 13, 14, 15…”

Section: Introductionmentioning

confidence: 99%

Progress and Promise of Nitric Oxide‐Releasing Platforms

2018

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Nitric oxide (NO) is a highly potent radical with a wide spectrum of physiological activities. Depending on the concentration, it can enhance endothelial cell proliferation in a growth factor‐free medium, mediate angiogenesis, accelerate wound healing, but may also lead to tumor progression or induce inflammation. Due to its multifaceted role, NO must be administered at a right dose and at the specific site. Many efforts have focused on developing NO‐releasing biomaterials; however, NO short half‐life in human tissues only allows this molecule to diffuse over short distances, and significant challenges remain before the full potential of NO can be realized. Here, an overview of platforms that are engineered to release NO via catalytic or noncatalytic approaches is presented, with a specific emphasis on progress reported in the past five years. A number of NO donors, natural enzymes, and enzyme mimics are highlighted, and recent promising developments of NO‐releasing scaffolds, particles, and films are presented. In particular, key parameters of NO delivery are discussed: 1) NO payload, 2) maximum NO flux, 3) NO release half‐life, 4) time required to reach maximum flux, and 5) duration of NO release. Advantages and drawbacks are reviewed, and possible further developments are suggested.

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Section: Introductionmentioning

confidence: 99%

Progress and Promise of Nitric Oxide‐Releasing Platforms

2018

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“…At the conclusion of the 3 month phase of the studies, pooled data from the studies showed significantly lower IOP in the LBN group compared with the timolol group at all time points (least squares mean IOP in the study eye ranged from 17.8 to 18.9 mmHg and from 19.0 to 19.7 mmHg, in the LBN 0.024% QD group and timolol 0.5% BID group, respectively) (Table ). Furthermore, the proportion of patients reaching an IOP of ≤18 mmHg was greater in the LBN group compared with the timolol group (Medeiros et al ., ; Weinreb et al ., ; Kaufman, ). Pooled results from the APOLLO and LUNAR open‐label safety extension phases demonstrated that the IOP reduction reached with LBN 0.024% was maintained up to 12 months, with no apparent loss of activity over time (Vittitow et al ., ).…”

Section: Pg Analogues As Ocular Hypotensive Agentsmentioning

confidence: 99%

“…The APOLLO (Weinreb et al ., ) and LUNAR (Medeiros et al ., ) studies were nearly identically designed phase 3 safety and efficacy studies of LBN 0.024% in patients with open‐angle glaucoma or ocular hypertension. Each study consisted of a 3 month active (timolol) comparator, double‐masked efficacy phase followed by a 9 month (APOLLO) or 3 month (LUNAR) open‐label safety extension (Table ).…”

Section: Pg Analogues As Ocular Hypotensive Agentsmentioning

confidence: 99%

Prostaglandin analogues and nitric oxide contribution in the treatment of ocular hypertension and glaucoma

Impagnatiello

Bastia

Almirante

et al. 2018

British J Pharmacology

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In patients with ocular hypertension or glaucoma, all treatments aim to lower intraocular pressure (IOP) by modulating aqueous humour (AH) production and/or uveoscleral and trabecular meshwork/Schlemm's canal AH drainage. PG analogues are considered to be the 'gold standard' treatment and are the most frequently used IOP-lowering agents. Recent data support an important role for NO in regulating IOP. Thus, novel PG analogues carrying a NO-donating moiety were recently advanced. Latanoprostene bunod (LBN) and NCX 470, NO-donating derivatives of latanoprost and bimatoprost, respectively, are examples of such compounds. LBN ophthalmic solution, 0.024% (Vyzulta™), showed greater IOP-lowering efficacy compared with that of Xalatan (latanoprost ophthalmic solution, 0.005%) or 0.5% timolol maleate in clinical settings. NCX 470 was found to be more effective than bimatoprost in animal models of ocular hypertension and glaucoma. Selective EP receptor agonists (i.e. taprenepag isopropyl, omidenepag isopropyl and aganepag isopropyl) and non-selective prostanoid receptor agonists (i.e. ONO-9054, sepetaprost isopropyl) that concomitantly stimulate FP and EP receptors have also been shown to hold promise as effective IOP-lowering agents.

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“…Thus, in principle, the two different outflow pathways can be enhanced simultaneously. In phase 3 trials, a drug product containing 0.024% API dosed once a day was superior at all but one of the time points to the 0.5% timolol drug product dosed twice a day (Medeiros et al, ; Weinreb et al, ). The FDA approved this drug product, brand name Vyzulta™, in late 2017.…”

Section: Future Directions In Pg‐based Therapymentioning

confidence: 99%

Discovery, characterization and clinical utility of prostaglandin agonists for the treatment of glaucoma

Klimko

Sharif

2018

British J Pharmacology

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Topical ophthalmic formulations of analogues of the endogenous arachidonic acid cyclooxygenase metabolite, PGF , are the standard of care treatment for the blinding disease glaucoma. These are the most potent and efficacious medical therapies for lowering intraocular pressure (IOP), the most important risk factor identified for disease progression. They have few side effects and offer the convenience of once-a-day dosing. It was initially believed that endogenous PGs raised IOP and caused substantial ocular surface adverse effects. However, carefully designed experiments demonstrated that esterification of the carboxylic acid afforded potent and efficacious topical ocular hypotensive activity. The final hurdle to be overcome was improvement of the side effect profile. A hypothesis was advanced that the IOP-lowering effect of PGF isopropyl ester was due to activation of its cognate PG-FP receptor, while side effects were largely due to promiscuous interaction with other PG receptors. This hypothesis was validated by modification of the ω chain (carbons 13-20) to a phenyl group. This provided the first marketed FP-class PG agonist analogue (FP-PGA) ocular hypotensive agent, latanoprost. Since the introduction of latanoprost into clinical medicine to lower and control IOP, a number of additional FP-PGAs have been discovered, characterized and marketed, including travoprost, tafluprost, unoprostone isopropyl ester and bimatoprost (an amide).

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Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study

Abstract: LBN 0.024% QD in the evening was noninferior to timolol 0.5% BID over 3 months of treatment, with significantly greater IOP lowering in subjects with OAG or OHT at all but the earliest time point evaluated, and demonstrated a good safety profile.

Cited by 90 publications

References 39 publications

Progress and Promise of Nitric Oxide‐Releasing Platforms

Progress and Promise of Nitric Oxide‐Releasing Platforms

Prostaglandin analogues and nitric oxide contribution in the treatment of ocular hypertension and glaucoma

Discovery, characterization and clinical utility of prostaglandin agonists for the treatment of glaucoma

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