Second pivotal trial confirms IOP-lowering efficacy of first-in-class agent

Take-home message: Results from a second pivotal trial investigating latanoprostene bunod 0.024% (LBN) are consistent with another identically designed study showing that not only is LBN non-inferior to timolol maleate 0.5% for lowering IOP, but it has significantly greater efficacy.

By Cheryl Guttman Krader; Reviewed by Felipe A. Medeiros, MD, PhD  

San Diego-Once-daily treatment with latanoprostene bunod (LBN) 0.024% ophthalmic solution (Bausch + Lomb) is safe, effective, and well-tolerated for lowering IOP in patients with open-angle glaucoma and ocular hypertension. That’s the affirmation from published results of a second phase III clinical trial.

Data from the LUNAR study investigating the novel nitric oxide-donating prostaglandin F2α analogue were published online in the American Journal of Ophthalmology on May 19, 2016, and are consistent with findings from the phase III APOLLO study that appeared online ahead of print in Ophthalmology in February 2016.

Both double-masked trials randomly assigned adults with open-angle glaucoma or ocular hypertension 2:1 to treatment with LBN in the evening plus vehicle in the morning or twice daily treatment with timolol maleate 0.5%.

Follow-up visits were scheduled after 2 weeks, 6 weeks, and 3 months, and IOP measurements were obtained at 8 a.m., 12 p.m., and 4 p.m. at each visit.

The primary objective of the studies was to demonstrate the non-inferiority of the mean IOP-lowering effect of LBN to timolol over the 3-month treatment period. If that endpoint was met, statistical superiority of LBN to timolol was evaluated as a secondary objective.

LBN met the primary and secondary objectives in both studies, and the review of adverse event data and vital sign measurements showed no unexpected safety concerns associated with its use.

LBN is thought to increase aqueous humor outflow through a dual mechanism, according to Felipe A. Medeiros, MD, PhD.

“It is rapidly metabolized upon instillation in the eye to latanoprost acid, a prostaglandin analogue that increases uveoscleral outflow, and nitric oxide, an important physiological signaling molecule that regulates aqueous humor outflow through the trabecular meshwork/Schlemm’s canal pathway,” he said.

Dr. Medeiros is professor of ophthalmology, University of California, San Diego, and lead author of the published paper reporting results of the LUNAR study.

“If approved, LBN would be the first nitric oxide-donating prostaglandin analogue on the market and would be a welcome addition for offering a new therapeutic alternative for ophthalmologists and their patients with open-angle glaucoma or ocular hypertension,” he said.

The LUNAR Study

A total of 420 patients were randomly assigned for LUNAR. The two study groups were well-matched in their demographic and baseline ocular characteristics. Mean diurnal IOP was 26.6 mm Hg in the LBN group and 26.4 mm Hg in the timolol-treated patients.

Mean IOP reduction and mean IOP were analyzed as primary efficacy outcome measures. Across the nine time points assessed, LBN was associated with mean IOP reductions of 29.1% to 32.1% versus 25.2% to 28.7% for timolol. There were statistically significant differences favoring LBN over timolol in the analysis of mean IOP at all time points except at the 8 a.m. measurement at week 2.

Prespecified secondary efficacy outcome measures considered the proportions of patients that consistently achieved two IOP-lowering targets: ≥25% reduction from baseline and IOP ≤18 mm Hg.

The difference between LBN and timolol was statistically significant for the proportion of patients achieving a ≥25% reduction from baseline IOP (31.0% versus 18.5%; p = 0.007).

The proportion of eyes achieving an IOP ≤18 mm Hg was consistently numerically greater in the LBN group compared with timolol at all nine timepoints, but the difference in the overall proportion of patients achieving this target did not quite reach statistical significance (17.7% versus 11.1%; p = 0.084).

LBN was safe and well-tolerated. The most common treatment-emergent adverse events in LBN-treated eyes in both phase 3 trials were conjunctival hyperemia, eye irritation, eye pain, and instillation site pain.

LBN versus latanoprost

Data comparing LBN with latanoprost 0.005% (Xalatan, Pfizer) are available from the phase IIb VOYAGER study [Weinreb RN, et al. Br J Ophthalmol. 2015;99:738-745], a dose-ranging study that included more than 400 patients.

In VOYAGER, diurnal IOP reduction was greater in patients treated with LBN 0.024% compared with the latanoprost group at the primary endpoint on day 28, Dr. Medeiros noted.

“The benefit of LBN exceeded 1 mm Hg, and in VOYAGER there was also a statistically significant difference favoring LBN over latanoprost in an analysis of the proportion of patients who achieved a mean diurnal IOP ≤18 mm Hg at day 28,” he said. “This commonly used therapeutic target for patients with glaucoma was achieved by 68.7% of patients treated with LBN 0.024% versus only 47.5% of those treated with latanoprost.”

Felipe A. Medeiros, MD, PhD

E: fmedeiros@ucsd.edu

Dr. Medeiros has received institutional grant money from Alcon Laboratories, Allergan, Bausch + Lomb, Merck, and the National Eye Institute, and has served as a paid consultant for Alcon and Allergan.