NCX 470 Lowers Intraocular Pressure More Than Standard of Care in Glaucoma

Robert Fechtner, MD

Credit: LinkedIn

Results from the pivotal Mont Blanc phase 3 trial revealed the nitric oxide (NO)-donating prostaglandin analog, NCX 470, lowered intraocular pressure (IOP) more than latanoprost in patients with open-angle glaucoma and ocular hypertension.¹

In the randomized, controlled comparison, noninferiority versus latanoprost was established at all 6 study time points, and the safety profile revealed the agent was considered well-tolerated in the treatment of the ophthalmic conditions.

“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,” wrote the investigative team, led by Robert Fechtner, MD, professor, and chair of the department of ophthalmology, SUNY Upstate Medical University, and chairman of Nicox’s US Glaucoma Clinical Advisory Board.

NCX 460 is a novel nitric oxide-donating bimatoprost eye drop being evaluated in the United States and China for IOP-lowering in patients with open-angle glaucoma or ocular hypertension.

The Mont Blanc trial compared the IOP-lowering efficacy and safety profile of NCX 470 to latanoprost, an IOP-lowering eye drop formulation considered the standard of care in glaucoma treatment.² In the prospective, randomized, double-masked, parallel-group trial, patients were randomized to treatment with NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%.¹

An interim analysis was conducted to determine the final NCX 470 dose, after ≥30 participants in each trial group had completed the week 2 visit. Primary outcomes for the analysis were non-inferiority, followed by the superiority of NCX 470 compared with latanoprost, based on IOP reduction from baseline at 3 time points at 2 weeks, 6 weeks, and 3 months.

The analysis identified 691 individuals with open-angle glaucoma or ocular hypertension, with unmedicated IOP of ≥26 mmHg at 8 AM, ≥24 mmHg at 10 AM, and ≥22 mmHg at 4 PM in the study eye. The final study dose was deemed as NCX 470 0.1%. A total of 661 individuals were assessed and received NCX 470 0.1% (n = 328) or latanoprost (n = 333).

At the baseline, the mean IOP at 8 AM and 4 PM were 28.3 mmHg and 25.5 mmHg, respectively, in the NCX 470 0.1% group. These measures were significantly reduced at all treatment time points, with changes ranging from 8.0–9.7 mmHg (P <.0001) at each time point.

Meanwhile, the mean baseline IOP for the latanoprost group was 28.2 mmHg and 25.4 mmHg at 8 AM and 4 PM, respectively. These measures were significantly reduced at all on-treatment time points, with the reductions ranging from 7.1–9.4 mmHg (P <.0001 at each time point).

At the 3-month visit, the mean IOP reductions were greater with NCX 470 0.1% versus latanoprost 0.005% at all 6 study time points and significantly greater (P <.05) at 4 of the 6 study time points. Ultimately, the investigative team established the noninferiority of NCX 470 0.1% versus latanoprost at all 6 study time points.

Safety data showed the most common adverse event was conjunctival/ocular hyperemia, which was more common in the NCX 470 group compared with latanoprost. A total of 8 subjects in the NXC 470 and 6 subjects in the latanoprost group discontinued treatment owing to adverse events.

Topline results from the ongoing phase 3 trial of NCX 470, Denali, are expected in the second half of 2025.³ Currently, 80% of the target number of patients have been randomized in the trial and the completion of recruitment of US patients is anticipated by Q4 2024. Supportive development data required to prepare the New Drug Application (NDA) is expected to be available on or before the completion of the Denali trial.

“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,” said Doug Hubatsch, chief scientific officer of Nicox, in a statement.

References

1. _{Fechtner R, Mansberger S, Branch J, et al. 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. Am J Ophthalmol. Published online March 16, 2024. doi:10.1016/j.ajo.2024.03.002}
2. _{Tripathy K, Geetha R. Latanoprost. [Updated 2023 May 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540978/}
3. _{Nicox (2024) Results from Mont Blanc Phase 3 trial of Nicox’s NCX 470 in glaucoma published in the American Journal of Ophthalmology, GlobeNewswire News Room. Available at: 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 (Accessed: 21 March 2024)}