Mont Blanc Phase 3 glaucoma trial for NCX 470 achieves primary objective

NCX 470 0.1% was statistically superior to latanoprost 0.005% in intraocular pressure reduction from baseline at 4 of the 6 timepoints, and numerically greaterat all 6 timepoints.

Nicox SA today announced that once daily dosing of NCX 470 0.1% met the primary objective of non-inferiority in lowering intraocular pressure (IOP) compared to the standard of care, latanoprost 0.005%, in the 691-patient Mont Blanc Phase 3 clinical trial in patients with open-angle glaucoma or ocular hypertension.

According to a news release, the IOP-lowering effect from baseline for NCX 470 was 8.0 to 9.7 mm Hg vs. 7.1 to 9.4 mm Hg for latanoprost (reduction in time-matched IOP at 8 AM and 4 PM across the week 2, week 6 and month 3 visits).

In a pre-specified secondary efficacy analysis of time-matched change from baseline IOP, statistical superiority was not achieved, however the IOP reductions for NCX 470 were numerically greater than those for latanoprost at all 6 timepoints, and statistically significant (p<0.049) at 4 of the 6 timepoints. NCX 470, a novel nitric oxide (NO)-donating bimatoprost eye drop, is currently in a Phase 3 clinical program.

Andreas Segerros, CEO of Nicox, noted in the news release that the results demonstrate that NCX 470 has a robust intraocular pressure lowering effect, with good tolerability, and that it clearly met the primary objective of the Mont Blanc Phase 3 trial.

“NCX 470 is the first non-combination product to demonstrate statistical non-inferiority, and numerically greater intraocular pressure reduction, compared to a prostaglandin analog in a pivotal trial,” he said in a statement. “We are continuing to examine the Mont Blanc data including a number of additional ongoing pre-specified analyses which are important to fully define the profile of NCX 470, as well as further exploring NCX 470’sactivity on retinal cell protection, beyond its intraocular pressure lowering properties.”

NCX 470 Glaucoma Mont Blanc Phase 3 Topline Results Summary

• IOP-lowering effect from baseline was 8.0 to 9.7 mmHg for NCX 470 vs. 7.1 to 9.4 mmHg for latanoprost (reduction in time-matched IOP at 8 AM and 4 PM across the week 2, week 6 and month 3 visits).
• Non-inferiority was met vs. latanoprost in the primary efficacy analysis.
  The upper limit of the 95.1% confidence limit on the difference in the treatment effect between NCX 470 and latanoprost in change from baseline in time-matched IOP to the follow-up visits (week 2, week 6, and month 3) was ≤1.5 mmHg and ≤1.0 mmHg at all 6 timepoints.
• In a pre-specified secondary efficacy analysis of time-matched change from baseline IOP, NCX 470 was statistically superior (p<0.049) to latanoprost in intraocular pressure reduction from baseline at 4 of the 6 timepoints, and numerically greater at all 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 and latanoprost was up to 1.0 mmHg in favor of NCX 470.
• NCX 470 was well tolerated; the most common adverse event was ocular hyperemia in 11.9% of the NCX 470 patients vs. 3.3% of latanoprost patients. There were no ocular serious adverse events and no treatment-related non-ocular serious adverse events. 4.3% of patients on NCX 470 discontinued compared to 5.1% on latanoprost.

“We would like to acknowledge and thank all patients, clinical investigators and their teams for their contributions to the Mont Blanc trial, particularly during the challenging COVID-19 pandemic period.” said Doug Hubatsch, executive vice president and chief scientific officer of Nicox.

NCX 470 Phase 3 Trials Designs
Mont Blanc is a randomly assigned, 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 691 patients. Latanoprost is the most widely prescribed first-line therapy for open-angle glaucoma or ocular hypertension.

According to the company, the Mont Blanc trial enrolled 691 patients in 56 sites in the United States and one site in China. The primary efficacy evaluation was based on reduction from baseline in mean time-matched IOP at 6 timepoints: 8 AM and 4 PM at week 2, week 6 and month 3.

The similarly designed, ongoing, second Phase 3 trial, Denali, is being conducted at clinical sites in the U.S. and China, with topline results expected after 2024. The Denali trial also includes a long term safety extension through to 12 months, and is being jointly conducted and equally financed with our Chinese partner, Ocumension Therapeutics.