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    2015's glaucoma therapy advances

    New research aims to offer more convenient dosing for eye-drop medications

    While no new drug shook up the world of glaucoma in 2015, a variety of promising agents made incremental advances toward the market with their true potential as yet unproven. Manufacturers have continued to refine approaches to existing drugs.

    “We have limited drug choices and frequent side effects,” said Neeru Gupta, MD, PhD, MBA, professor and chief of Glaucoma, University of Toronto, with the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto. “Our surgical interventions are not without potentially serious complications. We’re looking for new drugs with a new target and minimal side effects.”

    Existing drugs can successfully lower IOP, but often cause irritating side effects. The inconvenience of applying multiple drops per day also makes adherence a challenge for many patients. 

    New mechanisms

    While a new non-prostaglandin drug is unlikely to replace prostaglandin analogues as the preferred first-line agent of choice in the near future, several drugs have the potential to be useful adjuncts to such therapy, according to Kuldev Singh, MD, MPH, professor of ophthalmology and director, Glaucoma Service, Stanford University School of Medicine, Stanford, CA.

    One drug, however, is fairly far along in the process for regulatory approval (Rhopressa, Aerie Pharmaceuticals). According to the manufacturer, the drug inhibits both Rho-kinase (ROCK) and noreprinephrine transporters.

    Related news: Improvements in glaucoma detection

    Rho-kinase plays a role in the transport of fluid out of the eye through the trabecular meshwork. Inhibiting this enzyme relaxes the trabecular meshwork in cells allowing fluid to exit. Noreprinephrine transporters are involved in producing aqueous fluid. The combination should result in less liquid production and a quicker exit for what is produced.

    Preclinical results have demonstrated that Rhopressa also lowers episcleral venous pressure, which contributes approximately half of IOP in healthy subjects, and may have an anti-fibrotic effect on the trabecular meshwork and the potential to increase perfusion of the trabecular meshwork, according to the company.

    In another potential advantage, the manufacturer noted it will offer the product in once-per-day doses rather than the two or three-per-day drop dosing required for many drugs on the market.

    The drug received mixed phase III results in 2015. In the Rocket-1 trial reported in April, the agent could not match the beta-blocker, timolol maleate, in lowering IOP in patients with baseline IOP below 27 mm Hg. In September, the company noted the product proved non-inferiority compared with timolol in Rocket-2, in subjects with baseline IOPs greater than 20 and below 25 mm Hg. The manufacturer said it is planning to file a new drug application (NDA) with the FDA by September 2016.

    Next: Another phase III trial

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