Eyeworld

EW GLAUCOMA 79 Unique options for improv- ing drug administration W hen it comes to glau- coma medication de- livery, virtually the only game in town has been drops. Now new options are winding their way through channels with some intrigu- ing possibilities, according to Gary D. Novack, Ph.D., president of PharmaLogic Development Inc., San Rafael, Calif. "Drops are good for local deliv- ery but they require the patients to take them sometimes one, two, and three times a day," Dr. Novack said. "Eye drops are challenging for some people to put in the eye." Dr. Novack cited a recent study that he and Alan L. Robin, M.D., associate professor of ophthalmology and associate professor of international health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, conducted together, which showed that only 20-30% of patients could put one drop in their eye without touching the bottle to the eye. Proper eye drop instillation re- quires patients to instill the drops at the right time in the right way. "Drops don't stay in the eye very long and even if the drug binds to something, it still requires relatively frequent dosing," Dr. Novack said. "There is an idea that we could cre- ate a delivery system that would not require so much from the patient." There has been a lot of work on systems over the last two decades and with a few exceptions, nothing has stuck, according to Richard A. Lewis, M.D., Sacramento, Calif. "The Ocusert (pilocarpine, Alza, Mountain View, Calif.) had a big re- lease of drug in the beginning and then slowed release at the end," Dr. Lewis said. "It caused a lot of side ef- fects." This system was ultimately discontinued. Drop delivery Some innovative approaches have been bandied about with the drops themselves. Over the years, thicken- ing agents have been tried. "The physician does that to create a longer residence time," Dr. Novack said. "The theory is that the drug stays in the eye longer and that longer presence results in a greater duration of efficacy." While this approach has successfully been used in antibiotics such as AzaSite (azithromycin, Inspire Pharmaceuti- cals, Raleigh, N.C.) and Besivance (besifloxacin, Bausch & Lomb, Rochester, N.Y.), so far no glaucoma company has pursued it to approval. One technique that is under consideration is to put the drug into a formulation known as a cationic exchange resin. Betoptic-S (betax- olol, Alcon, Fort Worth, Texas) is such a drop. Cationic exchange resins try to get the eye drop to re- lease over a slower period. "Electro- static attraction occurs between the droplets of the emulsion with the active ingredient," Dr. Novack said. "It is thought to allow that drug to hang around longer. This same ap- proach is being considered for la- tanoprost [Xalatan, Pfizer, New York]." Innovative devices In glaucoma, neuroprotection is an issue of particular import. "Allergan [Irvine, Calif.] has a product in clini- cal trial that is putting brimonidine (Alphagan) in the vitreous based on its ability to be neuroprotective," Dr. Novack said. "If we get brimonidine to the retina chronically, that might prevent the glaucomatous field pro- gression." This is something that is yet to be proven, he stressed. Some work is being done with punctal plugs. "There are some companies that are working on them and they're either using them for drug delivery in glaucoma or for antibiotic delivery, particularly after cataract surgery," Dr. Lewis said. "The drug is applied and left in place for a week as a punctal plug." There has, however, been some issues with the retention of the device and the duration of action. "There's a ten- dency for these plugs to slip out," Dr. Lewis said. "People rub their eyes and the plug falls out." Dr. Novack agreed that the plugs have been problematic. One com- pany, QLT Therapeutics (Vancouver, British Columbia), has put la- tanoprost on the plugs. "They are unable to get the same efficacy with this delivery system as with drops," he said. "Is that because they're not delivering enough drug, because they're not delivering it in the right way, or is it perhaps that latanoprost is a drug for which pulsatile delivery is needed?" Another company, Ocular Therapeutix (Bedford, Mass.), has put an antibiotic on the plugs. Use of ocular injection is an- other approach that has been stud- ied. "It's based on the treatment of macular degeneration by injecting a drug into the retina or in the vitre- ous to get control of the macular de- generation," Dr. Lewis said. "These drugs are being injected into the front of the eye to provide pressure reduction and lasting a long time— 6-12 months." It remains to be seen whether this will come to fruition. Still another unique approach is the use of Teflon strips. "The idea is taking a Teflon strip, freeze drying drug on it, and painting the eye with it," Dr. Novak said. This could potentially help with those who have trouble putting drugs in their eye and might be a way to get med- ications that aren't water soluble into the eye, he said. Overall, Dr. Lewis thinks that the big push in glaucoma drug treat- ment is going to be in such innova- tive drug delivery systems. While there are some new compounds in clinical trial now, this may slow going down the pike. "It's going to be a difficult hurdle to get a drug as safe and effective as the prostaglandins, which just went generic in March," Dr. Lewis said. "Therefore, I think that if a com- pany could develop a better drug delivery system, it could ask a pre- mium on the product." EW Editors' note: Dr. Lewis has financial interests with Alcon, Allergan, QLT, and Aerie Pharmaceuticals (Bridgewa- ter, N.J.). Dr. Novack is a consultant to many ophthalmic pharmaceutical firms, including ones that are interested in drug delivery. Contact information Lewis: 916-649-1515, rlewiseyemd@yahoo.com Novack: gary_novack@pharmalogic.com February 2011 September 2011 by Maxine Lipner Senior EyeWorld Contributing Editor Special delivery: Innovative drug systems in glaucoma Rho kinase continued from page 78 this class of drugs will surpass the prostaglandin analogues in efficacy," said Robert Fechtner, M.D., New Jersey Institute for Ophthalmology and Visual Science, Newark, "but they may provide a safe alternative for monotherapy. Local hyperemia appears to be the limiting adverse effect." He added, "It is intriguing to have the possibility of a modern trabecular meshwork outflow drug." Dr. Fechtner also speculated on the additivity of these drugs to prostaglandin therapy, as to date there has been little consensus on the optimal adjunctive therapy for patients needing more than a prostaglandin. "The mechanism of action for the prostaglandins is uveoscleral outflow. Will two out- flow drugs with different mecha- nisms show additivity?" EW Editors' note: The physicians mentioned have no financial intersts related to their comments. Contact information Fechtner: fechtner@umdnj.edu Mizuno: kmizuno@kowa.co.jp Realini: realinia@wvuh.com Serle: jserle@optonline.net Tanihara: tanihara@pearl.ocn.ne.jp EyeWorld factoid On average, it takes 12 years and millions of dollars to get one new medication from a laboratory to the pharmacist's shelf. Only five in 5,000 com- pounds that enter preclinical testing make it to human test- ing. One of these five tested in people is approved Source: Glaucoma Research Foundation

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