RHOKIINSA Eye drops, solution Ref.[49924] Active ingredients: Netarsudil

Pharmacotherapeutic group: Ophthalmologicals, antiglaucoma preparations and miotics
ATC code: S01EX05

Mechanism of action

Netarsudil, a Rho kinase inhibitor, is believed to reduce IOP by increasing outflow of aqueous humor. Studies in animal and man suggest that the main mechanism of action is increased trabecular outflow. These studies also suggest that netarsudil lowers IOP by reducing episcleral venous pressure.

Clinical efficacy and safety

A randomised, double-blind, multicentre Phase 3 clinical trial compared the efficacy and safety of netarsudil once daily with that of timolol maleate 0.5% twice daily in reducing IOP in a total of 708 patients with open-angle glaucoma or ocular hypertension. The median age of study participants was 65.5 years (range 18 to 91 years).

The study was designed to show non-inferiority of netarsudil when dosed once daily in the evening to timolol maleate 0.5% dosed twice daily in patients with a baseline IOP of >20 mmHg and <25 mmHg. The primary efficacy outcome measure was mean IOP at each of 9 timepoints measured at 08:00, 10:00 and 16:00 on day 15, day 43 and day 90. The non-inferiority margin applied was a difference in mean IOP ≤1.5 mmHg for all time points over all visits through 3 months and ≤1.0 mmHg at a majority of these time points. The IOP reduction with netarsudil dosed once daily was non-inferior to the effect of timolol 0.5% dosed twice daily in patients with baseline IOP of <25 mmHg (Table 1). Efficacy was also investigated in patients with baseline IOP ≥25 mmHg and <30 mmHg. Netarsudil demonstrated clinically relevant reductions in IOP at all timepoints, however non-inferiority to timolol was not demonstrated in this population with baseline IOP ≥25 mmHg and <30 mmHg (Table 2).

Table 1. Mean IOP by visit: PP population with baseline IOP <25 mmHg:

Table 2. Mean IOP by visit: PP population with baseline IOP ≥25 and <30 mmHg:

The safety of netarsudil has been evaluated in clinical studies, including four well-controlled Phase 3 studies.

Approximately 75% of subjects included in the netarsudil treatment groups of Phase 3 studies were Caucasian and 24% Black or African American. Over half were aged ≥65 years. With the exception of the incidence of cornea verticillata, no other difference in safety profile was observed between races or age groups (see section 4.8).

Completion rates in Phase 3 studies were lower in the netarsudil treatment group when compared with the timolol maleate group. Subjects with known contraindications or hypersensitivity to timolol were excluded from the studies. Discontinuation rates due to adverse reactions were 19.3% for the netarsudil treatment group versus 1.7% for the timolol maleate group. The majority of discontinuations in the netarsudil group were associated with ocular adverse reactions, whereas the majority of discontinuations in the timolol group were associated with non-ocular adverse reactions. The most frequently reported adverse reactions associated with discontinuation in the Rhokiinsa groups were conjunctival hyperemia (5.8%), cornea verticillata (3.7%) and vision blurred (1.4%). The incidences of hyperemia and vision blurred were sporadic in nature.

The efficacy and safety of netarsudil in subjects with compromised corneal epithelium or co-existing ocular pathologies e.g. pseudoexfoliation and dispersion pigment syndrome has not been established.

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with Rhokiinsa in all subsets of the paediatric population for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. (see section 4.2 for information on paediatric use).