Nicox’s NCX 470 Meets Phase 3 Goals, Supports NDA Filings in U.S. and China

Nicox has announced that its novel nitric oxide (NO)-donating bimatoprost eye drop, NCX 470 0.1%, has successfully met the primary endpoint in the Denali Phase 3 clinical trial. The investigational treatment demonstrated noninferiority in lowering intraocular pressure (IOP) compared to latanoprost 0.005%, a widely used glaucoma therapy.

Denali Phase 3 Trial Overview

The Denali study was a multicenter, randomized clinical trial involving 696 patients diagnosed with open-angle glaucoma or ocular hypertension. The once-daily administration of NCX 470 0.1% resulted in IOP reductions ranging from 7.9 to 10.0 mmHg. This was compared to latanoprost, which demonstrated IOP reductions between 7.1 and 9.8 mmHg. Measurements were taken as time-matched reductions at 8 a.m. and 4 p.m. across weeks 2, 6, and month 3.

Secondary Efficacy Outcomes and Statistical Analysis

In a prespecified secondary efficacy analysis, NCX 470 exhibited numerically greater IOP reductions at five of six timepoints. Statistical significance (P<0.05) was achieved at three of these timepoints, with the maximum difference recorded at 0.8 mmHg in favor of NCX 470. However, the study did not meet criteria for overall statistical superiority.

Consistency with Previous Mont Blanc Trial

The Denali trial findings mirror those of the earlier Mont Blanc Phase 3 trial completed in 2022. Both trials confirm NCX 470's strong efficacy and safety profile, reinforcing the drug's potential as a new therapeutic option for glaucoma management.

“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 3 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,” said Don Budenz, Coordinating Investigator of the Denali trial.

Safety and Tolerability

NCX 470 0.1% was generally well tolerated among patients. The most commonly reported side effect was conjunctival hyperaemia, observed in 22% of patients using NCX 470 compared to 9.2% in the latanoprost group. Importantly, there were no ocular serious adverse events or treatment-related non-ocular serious adverse events reported in the NCX 470 arm.

Discontinuation rates stood at 10.1% for NCX 470 versus 6.6% for latanoprost, with patients treated for up to 12 months. These long-term safety results are consistent with those observed in the Mont Blanc trial.

Regulatory Pathway and Strategic Partnerships

“With a second Phase 3 trial demonstrating the necessary efficacy and safety profile for submission of New Drug Applications – NDAs – in both the United States and China, we are now moving forward towards potential recurrent NCX 470 royalty revenue from 2027 onwards. Our established partnerships with Kowa and Ocumension enable us to accelerate NDA preparations, whilst also allowing us to focus on potential future strategies for the company,” said Gavin Spencer, CEO of Nicox.

Nicox has formed partnerships with Kowa and Ocumension to expedite the new drug application (NDA) process. A pre-NDA meeting with the U.S. Food and Drug Administration (FDA) is being planned in collaboration with Kowa. The company also intends to present additional clinical data at forthcoming ophthalmology conferences.