The NEI and subsequent trials have shown a need to achieve IOPs lower than we historically thought were appropriate,^1,2 and that many patients require additional therapy to reach a therapeutic target IOP.^3,4 Now, latanoprostene bunod (LBN, Nicox and Valeant Pharmaceuticals) is poised to receive FDA approval. LBN’s dual nature may change not only the multi-drug treatment pattern, but also our first-line medical treatment for glaucoma.

LBN is a prostaglandin agonist and nitrous oxide contributor. Latanoprostene improves outflow through the uveoscleral pathway. The bunod (butanediol mononitrate) releases nitrous oxide, which relaxes the trabecular smooth muscle and activates the soluble guanylate cyclase-cyclic guanosine monophosphate signaling pathway, improving the conventional outflow network comprised of the trabecular meshwork, collector channels, and Schlemm’s canal.

Two multicenter phase 3 studies, APOLLO and LUNAR, compared the safety and efficacy of LBN 0.024% to timolol maleate 0.5% for open-angle glaucoma or ocular hypertension.^5,6 For 3 months, patients used LBN once before bedtime or timolol maleate twice per day. In the APOLLO study, IOP declined 8 to 9 mmHg for LBN and 6.5 to 7.5 mmHg for timolol maleate.⁵ The medications reduced IOP 7.5 to 8.8 mmHg and 6.6 to 7.9 mmHg, respectively, in the LUNAR study.⁶ In both studies, the rates of adverse effects were similar for the two medications. The most common problems were eye irritation and conjunctival hyperemia.

The VOYAGER study compared the safety and efficacy of LBN 0.024% to latanoprost 0.005%.⁷ Study participants were randomized to use one drop of either medication in the evening. LBN lowered IOP on average 1.23 mmHg more than latanoprost. Adverse events were higher for LBN, but mostly minor and transient.

Evidence points to LBN having greater efficacy than our most commonly used prostaglandin analogues, with similar side effects. Additionally, LBN worked for patients with pressures considered to be in the normal range, making it one of the few drugs to demonstrate significant efficacy in this population in a phase 3 trial.^5-7

EXCITING POTENTIAL

Prostaglandins are the first-line standard of care and the foundation for future therapy. If the first medication we prescribe doesn’t adequately lower IOP, we generally add a second medication or consider laser or incisional surgery. Thus, it is very important to start with a medication that has the best chance of reaching the target pressure; LBN may offer a powerful solution to reach that target pressure.

Additionally, patients don’t like using multiple medications. The added inconvenience, discomfort, cost, and other factors make compliance a greater challenge. Several studies suggest that medical compliance among glaucoma patients is poor; 20% to 66% of patients don’t use their medication as prescribed.⁸ If IOP is an extra mmHg or more lower with LBN, we may reach the target pressure while avoiding the need for a second bottle.

Unlike traditional prostaglandins that improve the secondary outflow mechanism (uveoscleral pathway), but have minimal effect on conventional outflow, LBN encourages the secondary mechanism and helps maintain and possibly improve natural outflow. For MIGS devices that bypass the trabecular meshwork and help restore the natural flow, LBN may help improve outcomes by maintaining the healthy function of the trabecular meshwork and/or canal, thereby maximizing the chance of the MIGS device improving natural outflow.

As studies indicate that lower target pressures prevent optic nerve damage and vision loss, LBN may give us an edge. As a first-line therapy, it could help patients that other prostaglandins do not and even prevent or postpone the need for secondary therapies. GP

References

1. Heijl A, et al; Early Manifest Glaucoma Trial Group. Arch Ophthalmol. 2002;120(10):1268-1279.
2. Musch DC, et al; the CIGTS Study Group. Ophthalmology. 2011;118(9):1766-1773.
3. Kass MA, et al. Arch Ophthalmol. 2002;120(6):701-713.
4. Lichter PR, et al; CIGTS Study Group. Ophthalmology. 2001;108(11):1943-1953.
5. Weinreb RN,et al. Ophthalmology. 2016;123(5):965-73.
6. Medeiros FA, et al. Am J Ophthalmol. 2016(5);168:250-259.
7. Weinreb RN, et al. Br J Ophthalmol. 2015;99(6):738-745.
8. Olthoff CM, et al. Ophthalmology. 2005;112(6):953-961.