BIMATOPROST GRENOD NCX 470

INTRODUCTION:

A unique glaucoma medication, containing a proprietary nitric oxide (NO) donating platform and Bimatoprost is under FDA review. This dual action investigational drug is called NCX 470, also known as bimatoprost grenod.

The U.S. regulatory review process was started in July 2026 after Kowa (Japan) submitted a New Drug Application (NDA) for NCX 470 to the U.S. FDA.

MECHANISM OF ACTION:

The agent is unique in that it combines two pharmacological approaches in a single molecule:

• Bimatoprost — a prostaglandin-analogue that promotes uveoscleral outflow.
• Nitric oxide (NO) — a signaling molecule that enhances aqueous humor outflow through the conventional trabecular pathway.

The novel drug lowers IOP by acting on both major aqueous outflow pathways. By targeting these pathways simultaneously, researchers hope to achieve substantial IOP reduction.

TRIALS:

NCX 470 has been studied in a Phase 2 trial, Dolomites and in a Phase 3b trial, Whistler, and a separate Phase 3 program is ongoing in Japan. Exploratory nonclinical studies in a well-defined model with optic nerve head and retina damage (ET-1-induced ischemia/reperfusion) investigated the NCX 470 effects beyond its IOP lowering properties. The results suggest that NCX 470 improves ocular perfusion and restores retinal function in damaged eyes compared to vehicle and to Bimatoprost and may therefore have protective properties for the retina. Beneficial effects of NCX 470 have additionally been demonstrated in an in vivo model of retinal cell damage.

NCX 470 has completed two major Phase 3 studies:MONT BLANC and DENALI.

In the MONT BLANC study, 661 participants were analyzed. NCX 470 0.1% produced IOP reductions of approximately 8.0–9.7 mmHg across the evaluated time points and showed greater mean IOP reductions than latanoprost at all six measured time points, reaching statistical significance at four of them. 

The DENALI Phase 3 program also met its primary non-inferiority objective compared with latanoprost, supporting the subsequent U.S. NDA submission. 

SIDE-EFFECTS:

Clinical trials have reported a few ocular adverse events, with conjunctival/ocular hyperemia among the most common in the MONT BLANC study. 

REFERENCES:

1. Impagnatiello F, Toris CB, Batugo M, Prasanna G, Borghi V, Bastia E, Ongini E, Krauss AH. Intraocular Pressure-Lowering Activity of NCX 470, a Novel Nitric Oxide-Donating Bimatoprost in Preclinical Models. Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6558-64. doi: 10.1167/iovs.15-17190. PMID: 26457541.
2. Fechtner R, Mansberger S, Branch J, Mulaney J, Ziebell S, Lopez K, Hubatsch D. A Randomized, Controlled Comparison of NCX 470, a Nitric Oxide-Donating Bimatoprost, and Latanoprost in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The MONT BLANC Study. Am J Ophthalmol. 2024 Aug;264:66-74. doi: 10.1016/j.ajo.2024.03.002. Epub 2024 Mar 16. PMID: 38499140.
3. Elena Bastia, Nicoletta Almirante, Michael V W Bergamini, Tomas Navratil, Marlene Woodruff Modi, Francesco Impagnatiello; Nonclinical development of NCX 470, a novel nitric oxide (NO)-donating,IOP lowering prostaglandin analog for glaucoma and ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3806.
4. https://www.medchemexpress.com/bimatoprost-grenod.html?srsltid=AfmBOoqkr0sgp5DyMOu0TSKUe5sxKE2dgM0ZfAJ8cMNEvT1SnmcggQ9l