IOP LOWERING

Latanoprostene bunod, a novel investigational IOP-lowering agent combining a prostaglandin analogue with a nitric oxide (NO) donating moiety, has produced promising results in early clinical trials.

The new agent demonstrated greater efficacy and similar safety compared with latanoprost 0.005 per cent in a Phase 2b clinical trial. Now, Phase 3 studies are under way evaluating it as a treatment for patients with glaucoma and ocular hypertension.

The Phase 2b study was a dose- ranging trial that compared four different concentrations of latanoprostene bunod against latanoprost 0.005 per cent in patients with ocular hypertension or open angle glaucoma whose IOP was between 26 and 32 mmHg. Results for the groups treated with latanoprostene bunod 0.024 per cent (83 patients), the most efficacious and well tolerated concentration tested, and latanoprost 0.005 per cent (82 patients) were reported in a poster presented at the 2013 annual meeting of the Association for Research in Vision and Ophthalmology.

Assigned study           
Patients used their assigned study medication once nightly for 28 days and returned for IOP measurements on days seven, 14, 28, and 29. Mean diurnal IOP reduction was significantly greater in the latanoprostene bunod group compared with latanoprost on days seven (8.3 vs. 7.3 mmHg), 14 (8.9 vs. 7.7 mmHg), and 28 (9.0 vs. 7.8 mmHg). In addition, the proportion of patients achieving a mean diurnal IOP of 18 mmHg or less was significantly greater in the latanoprostene bunod group than in the control arm at all follow-up visits.

Safety analyses showed all treatment- emergent adverse events were mild or moderate in severity and similar in type and frequency in the latanoprostene bunod and latanoprost groups. Reports of stinging upon instillation were slightly higher for the investigational agent.

“For the past 17 years since latanoprost was first approved by the US FDA, prostaglandin analogues have been our most potent class of IOP-lowering drugs.

However, the search has continued for new compounds that are even more powerful but still offer the benefit of once daily dosing,” said L Jay Katz, MD, lead author of the poster, and director of the glaucoma service, Wills Eye Institute, and professor of ophthalmology, Thomas Jefferson University, Philadelphia.

Dual mechanisms
“The Phase 2b study results for latanoprostene bunod are encouraging as they suggest it may lower IOP more effectively than a prostaglandin analogue without compromising safety and tolerability. Now we await the results from the Phase 3 studies that will provide data on longer term use from a larger population.”

As NO has been shown to relax the trabecular meshwork and ciliary muscle, NO donors are thought to lower IOP by improving aqueous outflow through the trabecular meshwork. “In theory, the increased potency of latanoprostene bunod might be explained by its having a dual mechanism of action, increasing uveoscleral outflow because of the latanoprost component, but also enhancing trabecular outflow,” said Dr Katz.