Nicox SA released findings from a recent analysis of the phase 3 Mont Blanc clinical trial evaluating the investigational formulation NCX 470 for the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT).
These latest numbers were presented during the 2025 American Glaucoma Society annual meeting, Feb. 26-March 2, in Washington, DC.
Where to begin?
We’ll start with NCX 470.
What it is: A novel nitric oxide (NO)-donating bimatoprost formulation with intraocular pressure (IOP)-lowering components (of NO) and prostaglandin analogs (PGAs).
A couple of notes about these components:
- Quick NO rundown: This contains small, naturally occurring signaling properties with key involvement in IOP regulation—all through the activation of soluble guanylate cyclase (sGC).
- About sGCs: As key enzymes of the NO signaling pathway, these regulate blood pressure and blood vessel relaxation.
- What to know about PGAs: Already widely used, this class of drugs is considered convenient and effective for the initial lowering of IOP in OAG and OHT patients.
- Check out these branded versions of bimatoprost already on the market
Explain how NCX 470 works.
It’s pretty simple: The drop is formulated to release bimatoprost and NO into the eye—ideally resulting in a reduction in IOP via two different pathways in its target patients (OAG and OHT).
What makes this unique: The NO-bimatoprost combo features a dual mechanism of action (MOA) that has reportedly been clinically proven to achieve superior IOP-lowering compared to just bimatoprost alone, according to Nicox.
And where’s the clinical data to back that statement up?
Already published. Specifically, in 2021.
The details: Exploratory in vivo studies evaluated NCX 470 in a nonclinical model of retinal cell damage induced by endothelin-1 (ET-1) for its potential protective effects on the retina and optic nerve head.
- What the findings suggested: Nicox reported that NCX 470 may improve ocular perfusion and retinal function in damaged eyes (versus vehicle) and—as a result—have therapeutic properties beyond just lowering IOP.
Interesting … now let’s get a rundown on this phase 3 study.
One of two phase 3 studies (the other being Denali [NCT04630808]), the Mont Blanc trial (NCT04445519) was initiated in 2020 and officially concluded in 2022.
The study details:
- Design: Randomized, adaptive dose-selection, multi-regional, double-masked, parallel group
- The participants: 670 patients (aged 18-84) diagnosed with OAG or OHT in both eyes
- The setup: Randomized to receive one of the following, dosed twice daily (BID) to both eyes (8 a.m. and 4 p.m.)
- NCX 470 0.1%
- NCX 470 0.065%
- Latanoprost 0.005%
- The outcome measures (time frame: 3 months):
- Primary: Reduction from baseline IOP in the study eye
- Secondary: See here
Before we get to this updated analysis, didn’t the company already report data?
Indeed they did. Multiple times over, in fact.
- Nicox reported in October 2022 that the study had achieved its primary objective—demonstrating noninferiority to latanoprost—with NCX 470 exhibiting an IOP lowering of 8.0 to 9.7 mmHg from baseline.
- Compare this to latanoprost’s 7.1 to 9.4 mmHg.
- In April 2024: The positive data continued, with the NCX 471 group reporting at baseline a mean (SD) IOP of 28.3 (2.0) mmHg at 8 a.m. and 25.5 (2.5 mmHg) at 4 p.m.
- Compare this to 28.2 (2.0) mmHg at 8 a.m. and 25.4 (2.4) mmHg at 4 p.m.
And which of these NCX 470 doses determined the final dose?
That would be the 0.1% dosage.
Got it. On to these updated findings.
Nicox reported that a statistically significant greater proportion of eyes treated with NCX 470 0.1% achieved mean diurnal IOP of ≤18 mmHg compared to those in the latanoprost 0.005% group.
Plus: A greater mean percent of IOP reductions from baseline were observed in eyes treated with NCX 470 versus those treated with latanoprost.
Let’s analyze this.
The company noted “key differentiating factors” between NCX 470 and latanoprost observed in the post hoc analysis of the study, with:
- A mean percentage reduction in IOP was greater on NCX 470 than latanoprost
- For eyes with an initial IOP of ≤ 28 mmHg: From baseline, the IOP-lowering effect was statistically significantly greater for NCX 470 versus latanoprost (for all timepoints measured)
- Regardless of baseline IOP, NCX 470 demonstrated consistent IOP lowering versus the latanoprost-based IOP reduction
- The number of patients receiving NCX 470 who showed an IOP reduction > 10 mmHg from baseline was a “statistically significant greater proportion” versus latanoprost
Go on …
Nicox emphasized that, despite NCX 470 failing to meet statistical superiority to latanoprost in a pre-specified secondary efficacy analysis of time-matched change from baseline IOP, “NCX 470 was numerically superior to latanoprost at all time points and statistically significant (p<0.049) at 4 of 6 timepoints.”
And overall?
The study determined (and demonstrated) that NCX 470 “met the efficacy standard” for FDA approval in the United States (non-inferiority to latanoprost) with an IOP reduction of 8.0 to 9.7 mmHg.
- Keep in mind: Both the Mont Blanc and Denali studies were approved to support an eventual new drug application (NDA) submission for the candidate.
And with that NDA submission in mind … what’s next for the candidate?
The company is currently on track to target a potential H1 2026 NDA submission for NCX 470.
And in the meantime, Nicox previously reported the following expected updates on the formulation in its Q4 2024 report:
- Data from the phase 3b Whistler trial (initiated in December 2023) are expected before the end of Q1 2025
Topline results from the phase 3 Denali trial are expected in Q3 2025