EyeWorld Asia-Pacific December 2016 Issue

EWAP SECONDARY FEATURE 31 December 2016 by Michelle Dalton, EyeWorld Contributing Writer New glaucoma treatments in development Leading experts offer their opinions on some of the compounds now in clinical trials T opical pharmacologic treatments for glaucoma have not varied drastically in the past few decades, but that may be about to change. Traditionally, medications reduce aqueous production or improve aqueous outflow, increase uveoscleral outflow, or affect the episcleral venous pressure. “We now have the potential to have one product that will cover all four mechanisms of action. There’s the potential of really making an impact in the space,” said Steven Vold, MD , founder and chief executive officer, Vold Vision, Fayetteville, Arkansas. Aerie Pharmaceuticals (Waltham, Massachusetts) is about to file netarsudil, a Rho- kinase inhibitor, for the treatment of primary open-angle glaucoma, and is in latestage development for its combination netarsudil and latanoprost; data on that drug should be available later this year, according to company sources. Bausch + Lomb (Bridgewater, New Jersey) has filed latanoprostene bunod for the treatment of primary open-angle glaucoma. That compound is based on latanoprost. “We’re now using trabecular outflow as a way of lowering pressure. Again, all those concepts of nurturing Views from Asia-Pacific Ivan GOLDBERG, MD Clincial Associate Professor, University of Sydney Floor 4, 187 Macquarie Street, Sydney, NSW 2000, Australia Tel. no. +612-9247-9972 Fax no. +612-9232-3086 eyegoldberg@gmail.com W hen topical beta-blockers became available for clinical use in 1978, they revolutionized glaucoma medical management; the prostaglandin analogues did the same some 20 years later. Topical carbonic anhydrase inhibitors and alpha-agonists made a lesser, but still significant contribution to patient visual safety by increasing medical options. Increased availability of fixed dose combinations helped improve patient convenience with multi-drop use. Now, almost 20 years after the arrival of latanoprost, ophthalmologists await approval and release of new classes of ocular hypotensive agents, working through different mechanisms. While new agents are unlikely to be “revolutionary”, they promise real advances and will increase medical treatment options for individual patients. Two different products that should be available shortly stand out: latanoprostene bunod (Bausch and Lomb, Bridgewater, New Jersey) and netarsurdil alone or in fixed combination with latanoprost (Aerie Pharmaceuticals, Waltham, Massachusetts). Latanoprostene bunod has a nitric oxide donating property that improves conventional outflow through the trabecular meshwork, augmenting latanoprost’s increase in uveoscleral outflow (with a possible trabecular component as well). While current data indicates that efficacy hasn’t been overwhelming, this product’s side effect/benefit balance is likely to find it a place in the treatment of a sizeable segment of the glaucoma patient population. Richard Brubaker’s computer simulations, recently confirmed with the water drinking provocative test, demonstrated that agents that enhance outflow have a more profound effect on dampening intraocular pressure (IOP) spikes both in amplitude and duration than do inflow inhibitors. While this advantage hasn’t been confirmed as visually protective by prospective studies, the implications for patient benefit are clear. As a rhokinase inhibitor, netarsurdil represents an entirely new drug class with new mechanisms of action. It has been reported to reduce IOP by decreasing aqueous production, by enhancing outflow and by lowering episcleral venous pressure. As a result of this last effect and unlike all other drug classes that lower IOP by a greater margin the higher the starting level, netarsurdil and its sibling ROC inhibitors seem to reduce IOP as significantly with lower initial IOPs as with higher starting levels. This finding suggests that these agents might prove particularly helpful for patients with optic nerve damage at more modest IOPs. Combining netarsudil with latanoprost in a fixed combination might well provide patients with a potent alternative to current products. How these new agents are able to be used in countries across our region will depend on regulatory approval and then on comparative costs with current drugs. In this era of cheap generics, new more expensive agents face several challenges. Nonetheless, with advances across the board in surgical techniques for IOP reduction, we live in exciting times: we can anticipate new choices for our patients medically as well. Editors’ note: Prof. Goldberg is a consultant for Alcon (Fort Worth, Texas), Allergan (Dublin), and Pfizer (New York) but has no financial interests related to his comments. continued on page 32