Novel IOP-lowering medication finds utility in glaucoma patient care

January 17, 2019

Latanoprostene bunod especially useful to patients who do not respond to first-line therapy

Latanoprostene bunod ophthalmic solution 0.024% brings a novel mechanism of action for IOP lowering and is proving to be a useful addition for patient care.

Reviewed by Andrew G. Iwach, MD

Latanopostene bunod ophthalmic solution 0.024% (LBN) (Vyzulta, Bausch + Lomb) is a safe and effective addition to the IOP-lowering treatment armamentarium, and seems to offer particular value for managing patients who do not respond adequately to traditional firstline therapy, including those with a lower initial IOP, said Andrew G. Iwach, MD.

“The introduction of latanoprost more than two decades ago dramatically changed management for patients with elevated IOP and because of its effectiveness, greatly helped reduce the need for glaucoma surgery,” said Dr. Iwach, executive director, Glaucoma Center of San Francisco, and co-founder, Eye Surgery Center of San Francisco, San Francisco.

“Compared with latanoprost, LBN provides a potential additional mechanism of action for IOP-lowering that explains why it may be even more effective and have a particular benefit in certain patients,” Dr. Iwach said.

Latanoprostene bunod is a nitric oxide (NO)- donating prostanoid FP receptor agonist that is metabolized in the eye into two moieties-the F2a prostaglandin analog, latanoprost acid, and butanediol mononitrate from which NO is released.

Latanoprost acid lowers IOP by increasing aqueous humor outflow through the uveoscleral pathway whereas NO introduces a second mechanism, increasing aqueous humor outflow through the trabecular meshwork and Schlemm’s canal.

Trial results evaluating LBN are consistent with the idea that its potential dual mechanism of action confers LBN with enhanced IOP-lowering activity.

Pivotal trials evaluating once-daily treatment with LBN 0.024% [LUNAR (Medeiros FA, et al. Am J Ophthalmol. 2016;168:250-259) and APOLLO (Weinreb RN, et al. Ophthalmology. 2016;123:965-973)] showed that it was significantly more effective than timolol 0.5% administered twice daily.

In the phase II VOYAGER study, LBN 0.024% was associated with a significantly greater reduction in diurnal IOP compared with latanoprost 0.005% [Weinreb RN, et al. Br J Ophthalmol. 2015;99:738-745].

Results of the open-label noncomparative JUPITER study [Kawase K, et al. Adv Ther. 2016;33:1612-1627] suggest LBN may have a niche role for treating patients with lower starting IOP.

In JUPITER, which was conducted in Japan and predominantly enrolled patients with a baseline IOP ≤21 mm Hg, the IOP reduction achieved with LBN 0.024% was similar to that reported for latanoprost 0.005% in a Japanese cohort with a baseline IOP ≥21 mm Hg. “Most ocular hypotensive medications drugs are more effective the higher the initial IOP,” Dr. Iwach said.

Practical considerations

Latanoprostene bunod is indicated for the reduction of IOP in patients with open-angle glaucoma or ocular hypertension and may be used as first-line therapy. Because of insurance coverage restrictions that often limit access to new entities, however, Dr. Iwach said that he generally prescribes LBN when patients have not achieved sufficient IOP-lowering with other first-line therapy, which for most patients is with latanoprost.

“In the VOYAGER study, the average reduction from baseline IOP was about 1 mm Hg greater with LBN compared with latanoprost, which may not seem that important,” Dr. Iwach said.

“However, there was a lot of variability in the response to LBN with some patients achieving an IOP reduction that was 3 to 4 mm Hg greater than the latanoprost mean. In practice we treat individuals, not averages, and the dramatic IOP-lowering activity seen with LBN in some clinical trial participants is consistent with my experience in daily practice that shows some patients can benefit with a marked improvement in IOP-lowering when switched from latanoprost to LBN,” he said.

Compared with adding a second agent to control IOP when patients do not respond adequately to latanoprost monotherapy, the transition to LBN comes without any penalty for increased dosing burden that can compromise patient adherence and subsequently efficacy.

“Simplifying the treatment regimen is critical for patients on IOP-lowering therapy who may need to use their medication for years,” Dr. Iwach said.

“In my experience, the switch from latanoprost to LBN has also been very smooth in terms of tolerability,” he said.

“All of the medications we use have potential side effects, but the safety profile of LBN seems similar to that of latanoprost and changing treatment to LBN has not resulted in a significant increase in patient complaints.”

Disclosures:

Andrew G. Iwach, MD
E: ai@glaucomasf.com
Dr. Iwach is a consultant to and on the speakers’ bureau for Bausch + Lomb.