Objective:

The article reports Nora Lee Cothran’s discussion of phase 3 DENALI findings for NCX-470 versus latanoprost in the US subpopulation.

Approach:

• Design and participants: DENALI was a randomized, double-masked, active-controlled study conducted at 90 sites worldwide, including 65 in the United States. The US subpopulation included 549 patients with primary open-angle glaucoma or ocular hypertension, randomized 1:1 to NCX-470 or latanoprost 0.005% after washout of prior glaucoma medications.
• Assessments: IOP was measured at weeks 2 and 6 and month 3, at 8:00 AM and 4:00 PM. The study goal was to investigate mean IOP reduction with NCX-470 versus latanoprost; Cothran reported that the noninferiority endpoint was met at all timepoints.
• Mechanism: NCX-470 (bimatoprost grenod 0.1%) is a nitric oxide-donating bimatoprost with two mechanisms of action. Cothran described its prostaglandin activity as acting on uveoscleral outflow and its nitric oxide component as acting on the trabecular meshwork and conventional outflow.

Key Findings:

• Cothran reported that NCX-470 met the noninferiority endpoint at all measured timepoints.
• IOP was lower with NCX-470 at all six timepoints; statistically significant changes in IOP were observed at three of the six timepoints.
• Cothran reported average IOP reduction of 8.1 to 10.1 mmHg in the NCX-470 arm.
• Cothran said NCX-470 was well tolerated and that no serious treatment-related adverse events occurred during the study.
• Cothran said the US-subpopulation safety and efficacy findings were consistent with phase 3 MontBlanc data submitted to the FDA for a new drug authorization.

Interpretation:

Cothran characterized the IOP differences as clinically meaningful. She said the AAO treatment guidelines for starting medication in newly diagnosed patients call for a 20% to 30% IOP reduction, and that this reduction was met or exceeded at each trial timepoint with NCX-470.

Limitations:

• The interview reports findings for the US subpopulation, not the full international DENALI population.
• The interview does not provide numerical between-group differences, confidence intervals, or adverse-event rates.
• The clinical-significance assessment and treatment perspectives are Cothran’s statements.

Conclusion:

In the US subpopulation of DENALI, Cothran reported that NCX-470 met the noninferiority endpoint at all measured timepoints and produced lower IOP at all six timepoints than latanoprost, with statistically significant changes in IOP at three timepoints. She also reported average IOP reduction of 8.1 to 10.1 mmHg and no serious treatment-related adverse events during the study.

Sources:

• Article context: interview with Nora Lee Cothran, OD, FAAO, following the AAO annual meeting