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NCX 470 Meets Phase III Goal in Glaucoma With Strong Intraocular Pressure Reductions
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Key Takeaways
- NCX 470 0.1% demonstrated non-inferiority to latanoprost in lowering IOP, with statistically significant superiority at several timepoints.
- The Denali trial showed NCX 470 was well tolerated, with conjunctival hyperemia as the most common adverse event.
The Denali trial confirmed non-inferiority of NCX 470 to latanoprost in lowering intraocular pressure, with consistent efficacy, favorable safety, and supportive results from the earlier Mont Blanc study.
Nicox has shared positive results from the Phase III Denali clinical trial (NCT04630808) evaluating its NCX 470 0.1%, a novel nitric oxide (NO)-donating bimatoprost eye drop, in patients with open-angle glaucoma or ocular hypertension. The study met its primary endpoint of non-inferiority in lowering intraocular pressure (IOP) from baseline compared to standard of care.1
Efficacy and safety results
Topline results from the Denali trial show:
NCX 470 demonstrated non-inferiority to standard of care latanoprost 0.005%.
- Mean IOP reductions from baseline ranged from 7.9 to 10.0 mmHg with NCX 470 0.1% compared to 7.1 to 9.8 mmHg with latanoprost, measured at 8 AM and 4 PM across week 2, week 6, and month 3 visits.
- In a prespecified secondary analysis, NCX 470 achieved statistically significant superiority (p<0.05) at 3 of 6 timepoints, and numerically greater reductions at 5 of 6 timepoints, with differences up to 0.8 mmHg in favor of NCX 470.
- NCX 470 was generally well tolerated, with conjunctival hyperemia as the most common adverse event (22.0% vs. 9.2% for latanoprost).
- No ocular serious adverse events or treatment-related non-ocular serious adverse events occurred in NCX 470 patients.
- Discontinuation rates were 10.1% for NCX 470 and 6.6% for latanoprost, including patients followed out to 12 months.
In a company statement, Don Budenz, coordinating investigator of the Denali trial, said: “The Denali trial results validate the robust therapeutic profile of NCX 470 observed in the Mont Blanc trial, replicating the efficacy and safety outcomes. Consistent results across the two large Phase III studies strengthen the case for regulatory submissions and support NCX 470’s potential as an important treatment option for glaucoma patients. I look forward to seeing further data presented at future ophthalmology meetings.”
Phase III Denali trial design
Denali is a randomized, multi-regional, double-masked, parallel group trial.
- A total of 696 patients were enrolled across 90 sites in the United States and China.
- The study also included a long-term safety extension to 12 months.
- Denali was jointly conducted and co-financed with Ocumension Therapeutics.
Consistency with Mont Blanc trial
As mentioned by Budenz, Nicox saw positive results from NCX 470 in the Phase III Mount Blanc trial (NCT04445519) in October 2022. In this study, the NO-donating bimatoprost eye drop once again demonstrated non-inferiority in lowering IOP compared to latanoprost, meeting the primary endpoint.2
In patients with open-angle glaucoma or ocular hypertension, data of NCX 470 from Mount Blanc showed:
- Mean IOP reduction from baseline ranged from 8.0 to 9.7 mmHg with NCX 470 compared to 7.1 to 9.4 mmHg with latanoprost, measured at 8 AM and 4 PM across week 2, week 6, and month 3 visits.
- In a prespecified secondary analysis, NCX 470 was statistically superior (p<0.049) to latanoprost at four of six timepoints and numerically greater at all six, with differences up to 1.0 mmHg in favor of NCX 470.
- NCX 470 was generally well tolerated. The most common adverse event was ocular hyperemia (11.9% vs. 3.3% for latanoprost).
- Discontinuation rates were 4.3% for NCX 470 and 5.1% for latanoprost.
Similar in design to the Denali trial, Mount Blanc was a randomized, multi-regional, double-masked, parallel group study that enrolled 691 patients across 56 sites in the United States and one in China.
In a company statement from the time of the Mount Blanc readout, Andreas Segerros, chief executive officer of Nicox, said: “These results demonstrate that NCX 470 has a robust intraocular pressure lowering effect, with good tolerability, and that it clearly met the primary objective of the Mont Blanc Phase III trial. NCX 470 is the first non-combination product to demonstrate statistical non-inferiority, and numerically greater intraocular pressure reduction, compared to a prostaglandin analog in a pivotal trial.”
References
1. Nicox Announces Positive Results from the NCX 470 Phase 3 Denali Trial in Glaucoma Patients. News release. Nicox. August 21, 2025. Accessed August 21, 2025. https://www.nicox.com/wp-content/uploads/EN_NCX470DenaliToplineAugust2025_PR_FINAL.pdf
2. Nicox Reports Achieving Primary Objective in Mont Blanc, the First Phase 3 Glaucoma Trial for NCX 470. News release. Nicox. October 31, 2022. Accessed August 21, 2025. https://www.nicox.com/wp-content/uploads/EN_NCX-470-MontBlanc-Phase-3-Topline-results-PR_20221031_F.pdf
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