Nicox SA announced the results of the Whistler phase 3b exploratory clinical trial investigating the dual mechanism of action (nitric oxide and prostaglandin analog) of NCX 470 in intraocular pressure (IOP) lowering in healthy volunteers and ocular hypertensive patients.
In a company press release, Nicox relayed that the Whistler phase 3b exploratory trial was a double-masked, placebo-controlled study designed to further the company's understanding of the action of NCX 470 ophthalmic solution, 0.1%, on various aqueous humor dynamic parameters in 18 healthy volunteers or subjects with ocular hypertension. Measurements were taken at baseline and after 8 days at 1 pm and, for some parameters, at 3 pm.
Changes in aqueous humor flow rate trended towards significance vs placebo (p=0.072). Outflow facility was positive at 1 pm (p=0.081), significant at 3 pm (p=0.001), as was the diurnal outflow (p=0.004). The company said it believes this change is due to the effect of nitric oxide on the trabecular meshwork.1 IOP lowering and uveoscleral outflow were statistically significant at all timepoints measured, whilst episcleral venous pressure did not show a notable trend. These findings support the dual mechanism of action for IOP lowering of NCX 470 through both the conventional (nitric oxide-stimulated) and the uveoscleral (prostaglandin-stimulated) pathways. The safety profile observed was consistent with that of the first phase 3 trial, Mont Blanc, the company said in the press release.
According to Nicox, the Whistler trial was an exploratory trial and is not a requirement for the submission of new drug applications for NCX 470 and therefore does not impact the development timeline. The patient population in the Whistler trial was primarily normotensive healthy volunteers with mean baseline IOPs of 16.6 mmHg and 16.9 mmHg for NCX 470 and placebo treated patients, respectively. This is not the same patient profile as in the phase 3 glaucoma program. Safety and efficacy have already been demonstrated in the first phase 3 clinical trial, Mont Blanc, the company said.
“We believe that the outcomes in favor of NCX 470 in several trabecular meshwork aqueous humour dynamics parameters are due to nitric oxide," said Doug Hubatsch, chief scientific officer of Nicox, in the press release. "These positive exploratory results suggest that further investigation may be warranted into the dual mechanism effect of NCX 470 on intraocular pressure. The therapeutic characteristics of NCX 470 demonstrated in the phase 3 program so far shows that we have an approvable and differentiated asset with a promising clinical profile. We look forward to announcing the safety and efficacy results from our ongoing phase 3 trial, Denali, expected in the third quarter of this year.”
1. For examples of the role of nitric oxide on these parameters, see Dismuke WM, Liang J, Overby DR, Stamer WD. Concentration-related effects of nitric oxide and endothelin-1 on human trabecular meshwork cell contractility. Exp Eye Res. 2014;120:28-35 and Wiederholt M, Sturm A, Lepple-Wienhues A. Relaxation of trabecular meshwork and ciliary muscle by release of nitric oxide. Invest Ophthalmol Vis Sci. 1994;35:2515-2520.