Nicox releases topline data from phase 3 Denali trial of NCX 470 in open-angle glaucoma or ocular hypertension patients

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Nicox has announced that the phase 3 Denali trial of NCX 470 0.1% met the primary endpoint of non-inferiority in lowering intraocular pressure (IOP) from baseline in open-angle glaucoma or ocular hypertension patients compared to the standard of care, latanoprost 0.005%.¹

NCX 470 is Nicox’s lead clinical product candidate and is a novel nitric oxide (NO)–donating bimatoprost eye drop that leverages the IOP-lowering effects of NO and prostaglandin analogs (PGAs) and is designed to release bimatoprost and NO into the eye to lower IOP by 2 different pathways in patients with open-angle glaucoma or ocular hypertension. NCX 470 incorporates Nicox’s proprietary NO-donating research platform and bimatoprost in a single molecule.²

The trial is a randomized, multi-regional, double-masked, parallel group trial that evaluated the safety and efficacy of NCX 470 ophthalmic solution, 0.1%, compared to latanoprost ophthalmic solution, 0.005%, in 696 patients in 90 sites in the US and China. It completed treatment and follow-up visits in June 2025.³

The Denali trial, together with the already completed Mont Blanc trial, was designed to fulfill the clinical regulatory requirements to support new drug application (NDA) submissions of NCX 470 in the US and China. Nicox estimates it will be submitting an NDA to the US FDA in the first half of 2026.

Denali phase 3 topline results

The IOP lowering effect from baseline was 7.9 to 10.0 mmHg for NCX 470 0.1% vs. 7.1 to 9.8 mmHg for latanoprost 0.005%. This was measured as a reduction in time-matched IOP at 8 AM and 4 PM across the week 2, week 6, and month 3 visits.

Additionally, in a pre-specified secondary efficacy analysis of time-matched change from baseline IOP, NCX 470 0.1% was statistically superior (p<0.05) to latanoprost 0.005% in IOP reduction from baseline at 3 of the 6 timepoints. NCX 470 was also numerically greater at 5 out of 6 timepoints but did not reach the overall statistical superiority pre-specified as a secondary efficacy endpoint. The difference in IOP reduction between NCX 470 0.1% and latanoprost 0.005% was up to 0.8 mmHg in favor of NCX 470.

The company noted that NCX 470 was well tolerated, with the most common adverse event being conjunctival hyperemia in 22% of the NCX 470 0.1% patients vs. 9.2% of latanoprost 0.005% patients. During the trial, 10.1% of patients on NCX 470 0.1% discontinued compared to 6.6% on latanoprost 0.005%, which includes patients out to 12 months.

The long-term safety profile is consistent with that seen in the shorter, 3-month, Mont Blanc trial.

Don Budenz, coordinating investigator of the Denali trial, stated, “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 2 large phase 3 studies strengthen the case for regulatory submissions and support NCX 470’s potential as an important treatment option for glaucoma patients.”

Nicox’s partnership with Kowa

In July 2025,⁴ Nicox and Kowa entered into an agreement regarding NCX 470 in which Kowa received exclusive rights to develop and commercialize NCX 470 in the US and all other territories of the world excluding Japan, China, Korea, and Southeast Asia. NCX 470 is exclusively licensed to Ocumension Therapeutics in China, Korea, and Southeast Asia. Kowa already has a license to NCX 470 for Japan, where it recently initiated a phase 3 safety clinical trial of NCX 470 in Japan for the treatment of ocular hypertension.⁵

According to the company, only 1 phase 3 confirmatory clinical trial in Japanese patients, plus the safety trial, is required for submission for marketing approval of NCX 470 in Japan.

Based on the results from the Denali trial, Nicox will receive a milestone payment of approximately $5.8 million (€5 million) from Kowa. Royalties on net sales in the US will start at 8%, with royalties also payable in other territories mentioned above. The total potential milestones payable under the agreement are valued at approximately $147.5 million (€127 million).

References:

1. Nicox Announces Positive Results from the NCX 470 Phase 3 Denali Trial in Glaucoma Patients. Published August 21, 2025. Accessed August 21, 2025. https://www.globenewswire.com/news-release/2025/08/21/3136836/0/en/Nicox-Announces-Positive-Results-from-the-NCX-470-Phase-3-Denali-Trial-in-Glaucoma-Patients.html

2. Portfolio and disease areas. Nicox SA. Accessed July 17, 2025. https://www.nicox.com/pipeline-markets-and-science/#product-ncx-470

3. Harp MD. Nicox completes phase 3 Denali trial of NCX 470 in open-angle glaucoma or ocular hypertension. Published June 30, 2025. Accessed August 21, 2025. https://www.ophthalmologytimes.com/view/nicox-completes-phase-3-denali-trial-of-ncx-470-in-open-angle-glaucoma-or-ocular-hypertension

4. Harp MD. Nicox and Kowa sign agreement for exclusive rights to glaucoma treatment NCX 470. Published July 20, 2025. Accessed August 21, 2025. https://www.ophthalmologytimes.com/view/nicox-and-kowa-sign-agreement-for-exclusive-rights-to-glaucoma-treatment-ncx-470

5. Harp MD. Kowa initiates phase 3 safety trial of NCX 470 in Japan. Published August 6, 2025. Accessed August 21, 2025. https://www.ophthalmologytimes.com/view/kowa-initiates-phase-3-safety-trial-of-ncx-470-in-japan