Nicox publishes results of Phase 3 trial of NCX 470 for treatment of glaucoma

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Nicox SA announced results from the Mont Blanc pivotal Phase 3 trial comparing NCX 470 to latanoprost in the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension have been published in the peer-reviewed journal American Journal of Ophthalmology.

According to the company, NCX 470 is a novel NO-donating bimatoprost eye drop currently in Phase 3 clinical development.

Robert Fechtner, MD, is the principal author, professor and chairman of the Department of Ophthalmology at SUNY Upstate Medical University, Syracuse, New York, and chairman of Nicox’s U.S. Glaucoma Clinical Advisory Board.

“We are pleased to see the publication of these data in such a recognized and respected journal,” Doug Hubatsch, chief scientific officer of Nicox, said in a news release.² “The data from the Mont Blanc Phase 3 trial demonstrated the potential of NCX 470 and we look forward to seeing confirmation of this clinical profile in the upcoming results from the ongoing Denali Phase 3 trial, expected in H2 2025. I’d also like to thank all the Mont Blanc study sites for their excellent work on this trial.”

The Mont Blanc Phase 3 trial is a prospective, phase 3, randomly assigned, adaptive dose-selection, double-masked, parallel-group trial that included 691 subjects with open-angle glaucoma or ocular hypertension and unmedicated IOP of IOP ≥ 26 mm Hg at 8 am, ≥ 24 mm Hg at 10am, and ≥ 22 mm Hg at 4 pm in the study eye.¹

The published study also noted that during the trial, participants were randomly assigned 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.

The participants were randomly assigned 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 8 am and 4 pm at 2 weeks, 6 weeks, and 3 months.¹

According to the study, 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 8 am and 4 pm was 28.3 (2.0) mm Hg and 25.5 (2.5) mm Hg, 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 mm Hg (p < 0.0001 at each time point).¹

The researchers also reported that mean (SD) baseline IOP at 8 am and 4 pm was 28.2 (2.0) mm Hg and 25.4 (2.4) mm Hg, respectively, in the latanoprost group and was significantly reduced at all on-treatment time points, with reductions ranging from 7.1-9.4 mm Hg (p < 0.0001 at each time point).

By 3 months, researchers found that the 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.

Moreover, the study found that 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.¹

“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,” the study concluded. “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.”

NCX 470, Nicox’s lead clinical asset, is a novel nitric oxide-donating bimatoprost eye drop. The Denali Phase 3 clinical trial evaluating NCX 470 for the lowering of IOP in patients with open-angle glaucoma or ocular hypertension, being conducted in the U.S. and China, is on track to generate topline results in H2 2025. Moreover, 80% of the target number of patients have been randomized in the trial and completion of recruitment of U.S. patients is expected in Q4 2024. Supportive development data required for the preparation of the U.S. New Drug Application (NDA) is expected to be available on or before the completion of the Denali trial.²

The database from the trial will not be locked until after the last patient has completed their final trial visit in China, which drives the timing of the Denali results.²

References:

1. Robert Fechtner, Steven Mansberger, James Branch, Sara Ziebell, Krisi Lopex, Doug Hubatsch. 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. American Journal of Ophthalmology. Published March 16, 2024. Accessed March 20, 2024. DOI: https://doi.org/10.1016/j.ajo.2024.03.002

2. NICOX. Results from Mont Blanc Phase 3 Trial of Nicox’s NCX 470 in Glaucoma Published in the American Journal of Ophthalmology. GlobeNewswire News Room. Published March 20, 2024. Accessed March 20, 2024. https://www.globenewswire.com/news-release/2024/03/20/2849092/0/en/Results-from-Mont-Blanc-Phase-3-Trial-of-Nicox-s-NCX-470-in-Glaucoma-Published-in-the-American-Journal-of-Ophthalmology.html