EyeWorld India September 2017 Issue

58 EWAP PHARMACEUTICALS September 2017 External photograph demonstrating sustained release punctal plug insertion for the reduction of intraocular pressure. Source: Ocular Therapeutix cause you’re not injecting it inside the eye.” It also wouldn’t have local skin-changing effects. Still, it is very early, with a lot of uncertainties. “The question is if the drug is going to get into the eye and how does it get in,” Dr. Budenz said. “Does it get in through the eye wall, or does it slowly elute through the hole that you made and get into the eye through the cornea? That wouldn’t be good because that hole is going to close up.” Internal approaches There are also intraocular drug de- livery systems. Dr. Aref said that the one furthest along is a bimatoprost sustained-release (SR) implant (Al- lergan) that is now in Phase 3 trials. The other is the travoprost im- plant (Envisia Therapeutics, Morris- ville, North Carolina). “They come on the tip of an injector, and the physician penetrates the anterior chamber of the eye and injects the implant into the front of the eye,” Dr. Aref said. “Once it’s inside the eye, it lowers the eye pressure the same way that an eye drop would.” The advantage of these over the punctal plug or ring is that the du- ration of effect is much longer. “The studies are suggesting that we’re getting 6 months of good efficacy, and perhaps with better iterations and improvements, we can get up to 9 months or even longer,” Dr. Aref said. Dr. Budenz reported that in Phase 2 studies the bimatoprost SR had as much as 8 to 10 mmHg pres- sure lowering at week 2. However, by week 26 the pressure lowering was at about 6 to 8 mmHg, de- pending upon the bimatoprost SR concentration, he noted. Currently, of the sustained-re- lease technology, Dr. Aref views the bimatoprost SR implant as poten- tially holding the greatest promise. “The reason is that even though it requires an injection into the eye and therefore carries slightly higher risk than the punctal plugs or the ring, it’s efficacious for a longer pe- riod of time,” Dr. Aref said. “With the plugs or with the ring, they are only efficacious for a 3-month period, then the patient is going to have to come back into the office.” This is something that is likely to create a great amount of stress on patient care, he thinks. Also, both the ring and the plugs can become dislodged, Dr. Aref pointed out. “With the ring, most of the time patients real- ize that it has been dislodged and they can notify their physician,” he said. “But with the punctal plug, there is a chance that the device can become dislodged and the pa- tient wouldn’t even know.” Still, with these external devic- es, the risk of complications is low, and they are often readily revers- ible. For example, if the wrong-sized ring is placed and causes discomfort or irritation, this can be removed and resized, Dr. Aref explained. He is optimistic about the appeal of the sustained-release ap- proach for patients. “I think that patients who have glaucoma are understandably anxious and scared about their disease because of the potential for blindness and at the same time cognizant that they may not be instilling the eye drops as directed, for reasons outside of their control,” he said. “I don’t think that patients are comfortable knowing that the major way to control their disease is in their hands.” For physicians, there are ques- tions that still need to be answered. It may be necessary, for example, for glaucoma patients to come in more frequently than they normal- ly would. “Physicians are going to have to figure out from an opera- tional perspective how to logisti- cally solve that issue,” Dr. Aref said, adding that the other main factor is how payment for these devices is going to work. “Is it going to be treated like a procedure where physicians get paid for implanting the device? If so, what is going to be the uptake from insurance carriers? Is this going to be something that they’re going to cover?” It remains to be seen whether they will want patients to try conventional eye drop therapy first, Dr. Aref said. Dr. Budenz concurred that the insurance piece of the issue needs to be sorted out. But in his view, there is room in the market for all of these sustained-release mecha- nisms. “I think that the intraocular injections are working better, but doctors aren’t going to want to stick needles in patients’ eyes every 4 to 6 months,” Dr. Budenz said. Like- wise, with the pellets, it’s unknown whether they are completely biode- gradable or build up over time, he continued. So for early glaucoma, he expects that the ring or plugs will be used. Overall, Dr. Budenz thinks there is likely to be widespread acceptance of the approach for doc- tors and patients. “The question is: Are payers going to pay for it? I hope they do because we’ve had a hard time getting drugs approved on the compliance argument alone, even though there is a lot of data saying that two-thirds of our patients don’t take their drops as prescribed,” he said. EWAP Editors’ note: Dr. Aref has finan- cial interests with Novartis (Basel, Switzerland) and New World Medical (Rancho Cucamonga, California). Dr. Budenz has financial interests with Allergan, Envisia, Alcon, Inotek Phar- maceuticals (Lexington, Massachu- setts), and Ivantis (Irvine, California). Contact information Aref: aaref@uic.edu Budenz: www.med.unc.edu/ophth Delivering on sustained – from page 57 “ Much of the progression we’re seeing is due to the troughs of efficacy of these medications when patients forget to use their medications. ” –Donald Budenz, MD