A Randomized, Controlled Comparison of NCX 470, a Nitric Oxide-Donating Bimatoprost, and Latanoprost in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The MONT BLANC Study

Purpose To compare intraocular pressure (IOP)-lowering efficacy and safety profile of NCX 470, a nitric oxide (NO)-donating bimatoprost, to latanoprost in subjects with glaucoma or ocular hypertension. Design Prospective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial. Methods: Participants 691 subjects with open-angle glaucoma or ocular hypertension and unmedicated IOP of IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye. Study Procedures: Subjects were randomized to treatment with NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. To identify the final NCX 470 dose, an interim analysis was performed after at least 30 subjects in each group had completed the Week 2 visit. Enrolled subjects were randomized to this final NCX 470 dose, 0.1%, or latanoprost for 12 weeks. Main outcome measure: We evaluated non-inferiority followed by superiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months. Results NCX 470 0.1% was the final dose and 661 subjects were analyzed that received NCX 470 0.1% (n=328) or latanoprost (n=333). At baseline, the mean (SD) IOP at 8AM and 4 PM was 28.3 (2.0) mmHg and 25.5 (2.5) mmHg, respectively, in the NCX 470 0.1% group, and was significantly reduced at all on-treatment time points, with reductions ranging from 8.0-9.7 mmHg (p<0.0001 at each time point). Likewise, mean (SD) baseline IOP at 8AM and 4PM was 28.2 (2.0) mmHg and 25.4 (2.4) mmHg, respectively, in the latanoprost group and was significantly reduced at all on-treatment time points, with reductions ranging from 7.1-9.4 mmHg (p<0.0001 at each time point). At the 3-month visit, mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (p<.05) at 4 of the 6 time points. Noninferiority versus latanoprost was established at all 6 timepoints. The most common adverse event was conjunctival/ocular hyperemia and was more common in the NCX 470 group compared to latanoprost; 8 NCX 470 and 6 latanoprost subjects discontinued due to adverse events. Conclusion The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with open-angle glaucoma or ocular hypertension at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.