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Novel glaucoma drug lowers IOP by unique combination of mechanisms

Article

In a study of normal volunteers, once-daily dosing of netarsudil mesylate ophthalmic solution 0.02% lowered IOP relative to baseline by increasing outflow facility and decreasing episcleral venous pressure.

A study of normal volunteers has shown once-daily dosing of netarsudil mesylate ophthalmic solution 0.02% (Rhopressa, Aerie Pharmaceuticals) lowered IOP relative to baseline by increasing outflow facility and decreasing episcleral venous pressure (EVP).1

Arthur J. Sit, MD, associate professor of ophthalmology, Mayo Clinic, Rochester, MN, and colleagues randomly assigned 10 healthy subjects (mean age 39 ± 14 years) to receive netarsudil 0.02% in one eye and its vehicle in the contralateral eye once daily in the morning for 7 days in a double-masked, vehicle-controlled, paired comparison study to evaluate the effect of netarsudil 0.02%, which inhibits Rho Kinase as well as the norepinephrine transporter, on aqueous humor dynamics (AHD).

It is generally accepted that aqueous humor secretion and outflow regulation are physiologically important in order to maintain IOP at a normal range.2 Both the ciliary body and the trabecular meshwork are key components of AHD. According to a review article, the uveoscleral outflow pathway “is relatively independent of the IOP,” and as people age, the proportion of aqueous humor leaving the eye decreases.2

 

Study methods, results

For this study, outflow facility was measured by digital Schiøtz tonography. EVP was measured by using an objective, computer-controlled venomanometer and image analysis software.

Aqueous humor flow rate was measured by anterior segment fluorophotometry. AHD variables measured at 1 week were compared with those measured at baseline.

Mean IOP in the treated eyes decreased from 17.0 ± 2.5 to 12.4 ± 2.2 mm Hg, compared with a decrease of only 0.7 mm Hg in the vehicle-treated eyes. Netarsudil-treated eyes showed an increase in outflow facility of 19% (p = 0.02) and a decrease in EVP of 9% (p = 0.01).

Outflow facility also increased in netarsudil-treated eyes (p < 0.001). Aqueous humor flow rate and uveoscleral flow rate did not change (p > 0.05). For the vehicle treated eyes, there was no change in any AHD variables.

Consistent with previous reports on netarsudil, subjects reported conjunctival hyperemia.

Looking forward

 

Looking forward

Netarsudil, if approved, would become “the only once-daily product available that, based on Aerie’s preclinical and clinical studies, specifically targets the trabecular meshwork,” the company has stated in press releases. “Preclinical and clinical studies have also demonstrated that [netarsudil] lowers episcleral venous pressure, which contributes approximately half of IOP in healthy subjects. Further, based on Aerie’s preclinical studies, [the product] may provide an additional mechanism that reduces fluid production in the eye and therefore lowers IOP.”

Aerie had said it will initiate phase I and II studies in Japan by year-end, and the FDA has now assigned a PDUFA date of Feb. 28, 2018 to rule on netarsudil for glaucoma and ocular hypertension.

Netarsudil also is being investigated in combination with latanoprost in the Mercury clinical studies.

 

References

1. Sit AJ, Kazemi A, McLaren JW, Kopczynski C, Heah TG, Novack GD. The effects of netarsudil ophthalmic solution on aqueous humor dynamics in humans. Poster presented at: ARVO 2017: Baltimore, MD: May 7, 2017. Abstract AO173.

2. Goel M, Picciani RG, Lee RK, Bhattacharya SK. Aqueous humor dynamics: A review. Open Ophthalmol J. 2010;4:52-59.

 

 

Arthur J. Sit, MD

P: 507/284-2511     E: sit.arthur@mayo.edu

This article was adapted from a poster presentation by Dr. Sit during the 2017 meeting of the Association for Research in Vision and Ophthalmology. Dr. Sit has received financial support from Aerie Pharmaceuticals Inc.

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