Nicox SA recently reported new positive clinical findings from its second phase 3 trial evaluating the daily dosing of NCX 470 0.1% among patients diagnosed with open-angle glaucoma (OAG) or ocular hypertension (OHT).
The data is the latest supporting a potential regulatory submission within the United States.
First up: this candidate.
At this point in our Nicox coverage, we’ve reported on NCX-470 quite a few times.
What it is: A novel nitric oxide (NO)-donating bimatoprost formulation that contains intraocular pressure (IOP)-lowering components (of NO) and prostaglandin analogs (PGAs).
- See here for details on NO (plus its unique mechanism of action [MOA])
- And click here for a PGA rundown (including the argument against their use)
About its dual MOA: The drop releases both bimatoprost and NO into the eye to reduce IOP—notably achieving a reported superior IOP-lowering effect than would be achieved using just bimatoprost.
- Ideally, this benefits both OAG and OHT patients
Now to this clinical research.
What to know: NCX 470 has undergone clinical evaluation in two phase 3 trials:
- The first: Mont Blanc (NCT04445519)
- The second: Denali (NCT04630808)
And an honorable mention in this phase 3 program is the phase 3b Whistler study (NCT05938699), an exploratory trial whose favorable results will notably not be included in a future new drug application (NDA) submission to the FDA.
- Why: Because the Mont Blanc and Denali studies have already demonstrated NCX 470 safety and efficacy—making the trials approved for inclusion in the NDA package (and requiring no further data).
And how has the candidate performed in that first phase 3 study?
As we reported earlier this year, pretty promising.
See here for a look at the positive data from the study, released back in October 2022, as well as the updated findings from March 2025 (which essentially determined the eye drop met the efficacy standard for FDA approval in the U.S.).
- And take note: This study also determined the final dosage (0.1%) for NCX 470 to be used in future testing.
Now to this second study: Denali.
Here’s what to know about the trial:
- Its design: Randomized, multi-regional, double-masked, parallel-group
- Its participants: 696 patients diagnosed with OAG or OHT in both eyes
- Its setup: Patient randomized 1:1 to receive either of the following administered to both eyes once daily in the evening:
- NCX 470 01%
- Latanoprost 0.005%
- The duration: Up to 12 months
And what was measured?
The primary endpoint was change from baseline IOP in the study eye, as determined by time-matched baseline at 8 am and 4 pm at the following visits:
- Week 2
- Week 6
- Month 3
Secondary outcomes: Change from baseline in diurnal IOP (up to 3 months) as well as treatment-emergent adverse events (AEs) and the rate of discontinuation, both measured at 12 months.
Next up: this topline data.
To start: The study met its primary objective (non-inferiority in lowering IOP from baseline compared to latanoprost).
- That IOP-lowering effect: 7.9 to 10.0 mmHg (for NCX 470) versus 7.1 to 9.8 mmHg (for latanoprost)
Break this lowering effect down by timepoints.
Compared to latanoprost, Nicox reported that IOP reductions for NCX 470 were “numerically greater” at five of the six timepoints.
- IOP reductions were also “statistically significant (p < 0.05) at 50% of those points.
However: Overall statistical superiority was not achieved.
Let’s talk tolerance and adverse events.
In all, NCX 470 was found to be “well tolerated.”
- As for AEs: There were no reports of any ocular serious AEs or treatment-related non-ocular serious AEs.
And before you ask: 10.1% of NCX 470-treated patients discontinued the study out to the 12-month mark (versus 6.6% of latanoprost-treated patients).
So how does this compare to the Mont Blanc trial data?
The company stated the results—including its long-term safety profile—are “consistent” with the earlier phase 3 trial (which concluded in 2022 and lasted only 3 months).
But more importantly: They also confirm the efficacy profile Nicox needed to move forward with a regulatory submission in the United States (and China).
Expand on those plans.
In the U.S.: The company recently partnered with Kowa Company, Ltd. to advance NCX 470 toward a potential FDA approval.
- About this partnership: Kowa will receive the exclusive rights to develop and commercialize NCX 470 in the United States and all other global territories excluding Japan, China, Korea, and Southeast Asia (that’ll go to Ocumension Therapeutics).
Nicox shared that—in collaboration with Kowa—it’s planning a pre-NDA meeting with the FDA.
So when might we expect an NDA submission?
Tentatively in the second half (H2) of 2026.