Fixed-Dose Combination of Netarsudil and Latanoprost in Ocular Hypertension and Open-Angle Glaucoma: Pooled Efficacy/Safety Analysis of Phase 3 MERCURY-1 and -2

Sanjay Asrani, Jason Bacharach, Edward Holland, Hayley McKee, Huan Sheng, Richard A Lewis, Casey C Kopczynski, Theresa Heah, Sanjay Asrani, Jason Bacharach, Edward Holland, Hayley McKee, Huan Sheng, Richard A Lewis, Casey C Kopczynski, Theresa Heah

Abstract

Introduction: New open-angle glaucoma (OAG) and ocular hypertension (OHT) therapies that reduce treatment burden and improve outcomes relative to currently available agents are needed. Netarsudil, a novel Rho kinase inhibitor approved by the US Food and Drug Administration, reduces intraocular pressure (IOP) by increasing trabecular outflow. Two phase 3 superiority studies compared a fixed-dose combination (FDC) of netarsudil and the prostaglandin latanoprost with each active component for IOP-lowering efficacy.

Methods: Pooled efficacy and safety data were analyzed from MERCURY-1 and -2 studies in patients with OAG or OHT. Patients instilled one drop of netarsudil (0.02%)/latanoprost (0.005%) FDC (n = 483), netarsudil (0.02%, n = 499), or latanoprost (0.005%, n = 486) into each eye once-daily between 20:00 and 22:00. IOP was measured at 08:00, 10:00, and 16:00 at weeks 2, 6, and the primary endpoint at month 3.

Results: Baseline mean diurnal IOP was 23.6, 23.6, and 23.5 mmHg in netarsudil/latanoprost FDC, netarsudil, and latanoprost groups, respectively. Mean diurnal IOP in each group was 15.3, 18.1, and 17.5 mmHg at week 2, 15.7, 18.4, and 17.4 mmHg at week 6, and 15.8, 18.4, and 17.3 mmHg at week 12. The netarsudil/latanoprost FDC met criteria for superiority compared with each active component (p < 0.0001 for all nine time points). At month 3, among patients randomized to netarsudil/latanoprost FDC or latanoprost, 58.4% vs 37.3% (p < 0.0001) achieved IOP ≤ 16 mmHg. Among patients randomized to netarsudil/latanoprost FDC or netarsudil or latanoprost, 30.9% vs 5.9% (p < 0.0001) vs 8.5% (p < 0.0001) achieved at least a 40% reduction from baseline in mean diurnal IOP. Pooled safety results were consistent with individual MERCURY studies.

Conclusion: Once-daily netarsudil/latanoprost FDC produced statistically significant and clinically relevant reductions in mean IOP that were statistically superior to IOP reductions achieved by netarsudil and latanoprost monotherapy. Results of the pooled efficacy and safety analyses were consistent with the individual studies.

Trial registration: ClinicalTrials.gov identifiers, NCT02558400 and NCT02674854.

Keywords: Clinical trial; Fixed-dose combination; Glaucoma; Intraocular pressure; Latanoprost; Netarsudil; Ocular hypertension; Prostaglandin analogue; Rho kinase inhibitor.

Figures

Fig. 1
Fig. 1
Mean intraocular pressure over 3 months. (ITT population) Post-baseline IOP is least-squares mean (± SE). Markov chain Monte Carlo methods were used to impute missing data. ***p < 0.0001 versus netarsudil and latanoprost. Mean IOP in the ITT pooled efficacy population is listed in the table below. CI confidence interval, FDC fixed-dose combination, IOP intraocular pressure, ITT intent to treat, SE standard error
Fig. 2
Fig. 2
Percentages of patients reaching prespecified categorical treatment targets at month 3. a Mean diurnal IOP (mmHg). b Percentage reduction from baseline in mean diurnal IOP. FDC fixed-dose combination, IOP intraocular pressure. ***p < 0.0001 vs. netarsudil and latanoprost from Fisher’s exact tests. Baseline refers to the visit 3 (day 1) data

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Source: PubMed

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