A Randomised, Controlled Comparison of Latanoprostene Bunod and Latanoprost 0.005% in the Treatment of Ocular Hypertension and Open Angle Glaucoma: the VOYAGER Study
Weinreb RN, Ong T, Scassellati Sforzolini B, Vittitow JL, Singh K, Kaufman PL; VOYAGER Study Group
Br J Ophthalmol. 2015;99:738-745
Study Summary
A new glaucoma drug, latanoprostene bunod (LBN) ophthalmic solution 0.024% (Vyzulta™), was approved by the US Food and Drug Administration in November 2017. Key to its approval was the VOYAGER Study. This randomized, investigator-masked study assessed the efficacy and safety of LBN compared with latanoprost 0.005%, and also led to the appropriate concentration being approved.
Conducted across 23 investigative sites (15 in the United States and eight in the European Union), the study enrolled 413 patients currently being treated and treatment-naive persons aged ≥ 18 years who were diagnosed with open-angle glaucoma or ocular hypertension in one or both eyes.
Four concentrations of LBN were studied to determine the optimum drug concentration to reduce intraocular pressure (IOP): 0.006% (n = 82), 0.012% (n = 85), 0.024% (n = 83), or 0.040% (n = 81). Eighty-two patients received latanoprost 0.005%.
The IOP had to be between 22-32 mm Hg and ≥ 24 mm Hg for at least two of three measurements at the baseline visit (which was considered the first day of the study) and after a 28-day washout period if applicable. Pretreated subjects were withdrawn from the study if the mean or median IOP was > 36 mm Hg in either eye at any point during the washout period.
One drop of study medication was instilled in the study eye(s) once daily in the evening for 28 days. Study visits occurred on days 1 (baseline), 7, 14, 28, and 29 (± 1 day for each). At each visit, IOP was measured at 8:00 AM, 12:00 PM, and 16:00 PM.
The primary efficacy endpoint was the reduction in mean diurnal IOP at day 28. The primary safety endpoint was the incidence of ocular and systemic adverse events and their severity and relationship to the study drug.
All treatments led to significant reductions in mean diurnal IOP from baseline at all follow-up visits. The LBN 0.006% and 0.012% groups also showed numerically greater reductions in IOP compared with the latanoprost group, but these differences were not significant. IOP reductions were dose-dependent and appeared to plateau with the 0.024%-0.040% dose, which were statistically significant compared with latanoprost.
The mean reduction in IOP at day 28 for each group was as follows: latanoprost, 7.77 mm Hg; LBN 0.006%, 7.81 mm Hg; LBN 0.012%, 8.26 mm Hg; LBN 0.024%, 9.00 mm Hg; LBN 0.040%, 8.93 mm Hg. A significantly greater proportion of subjects had mean diurnal IOP ≤ 18 mm Hg in the LBN 0.024% group at all visits (P ≤ .046).
The side effects of LBN were like those of latanoprost alone and included hyperemia and pain on instillation. Pain on instillation was reported by 6.1% of patients receiving latanoprost versus 12.0%-17.3% of those in the LBN groups. Hyperemia was reported by 8.5% of patients receiving latanoprost versus 1.2%-6.0% of those in the LBN groups.
Overall, LBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%.
Viewpoint
The study performed over multiple sites in the United States and Europe was a well-done controlled parallel-group study to determine not only the efficacy and side effects but also the optimal dosage of this glaucoma medication.
The study demonstrated that LBN is more efficacious at doses over 0.012%, with 0.024% being most optimal. Esterases in the eye cleave LBN into latanoprost acid and butanediol mononitrate, a nitric oxide (NO)-donating moiety. NO donors decrease IOP by activating calcium-activated potassium channels, which relax the trabecular meshwork and increase aqueous humor outflow.[1,2,3,4] The study concluded that there is a statistically significant greater reduction in IOP in patients using either LBN 0.024% or 0.040%, but the effect plateaued between those two doses. Therefore, the lowest efficacious concentration with the least increase in adverse outcomes was 0.024%, which is consistent with the now-available medication Vyzulta.
Given that the dosage regimen of LBN is the same as that of latanoprost, maintaining patients on a once-a-day dose may ensure the best adherence. Thus, in patients who may not be at their goal IOP on latanoprost alone, switching to LBN 0.024% may further reduce IOP, without the need to add a different second agent that may require more frequent dosing and decrease adherence. Furthermore, because the NO moiety is cleaved off by esterases in the ocular milieu, it may be possible to add this agent to other IOP-lowering agents, such as timolol or brimonidine. This may provide more options in the future for combination therapy for patients who have inadequate IOP control on their current regimen.
This newly approved agent seems to be a promising option to further reduce IOP in patients with open-angle glaucoma and ocular hypertension and increases our options for medical management in patients who may not have optimal IOP control on latanoprost alone.
Abstract: https://www.medscape.com/medline/abstract/25488946
Medscape Ophthalmology © 2018 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Shuchi B. Patel. 'Promising Option' for IOP Reduction - Medscape - Jun 14, 2018.
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