Eyeworld

EW GLAUCOMA 66 May 2016 by Michelle Dalton EyeWorld Contributing Writer bimatoprost," Dr. Craven said, but that one drop lowers IOP for 3–6 months with one implant. "It's a safer idea—drug expo- sure is less, the risk of side effects is reduced," he said. The biodegradable implant is placed intracamerally using a prefilled, single-use applica- tor system. Following washout and assessments at baseline (day –3 to –1), on treatment day 1, bimatoprost SR (6-, 10-, 15-, or 20-µg generation 2 formulation) was administered intracamerally in the study eye, and the fellow eye began topical bimato- prost 0.03% QD in a phase 1/2 pro- spective, 24-month, dose-ranging, paired eye comparison study. Study eyes that met retreatment criteria were allowed to receive a second ad- ministration of bimatoprost SR after a minimum of 90 days and at most 12 months after the first administra- tion. After delivery, the implant set- tles on the lower angle, Dr. Craven said. "At 12 months, there's a bit of the implant still in the bottom of the eye, but by 2 years it's complete- ly gone. The drug has been depleted before the implant dissolves." Over 16 weeks, the implant reduced IOP 7.2–9.5 mm Hg from baseline, de- pending on which version was used; topical bimatoprost reduced IOP 8.4 mm Hg from baseline. Both arms reported conjunctival hyperemia as the most common side effect, but within 2 days only 5 eyes in the im- plant group (of 75 overall) were still reporting hyperemia, compared to 13 eyes (of 75) in the topical group. While it's still early, Dr. Craven said "this looks like it's going to give us an expanded treatment option for a delivery platform that is very close to, if not as good as, what we saw with the drops with much less drug exposure and fewer side effects. It's promising." Subconjunctival injections Dr. Novack (with the Singapore Na- tional Eye Centre) investigated the use of a nanoliposome drug delivery system for the longer term delivery of latanoprost. 3 In that pilot study, a single subconjunctival injection of to make a scientific judgment at this point about which is the best delivery system," Dr. Novack said. "We don't have data yet on which ones will find the right balance of efficacy and safety and long enough delivery." Bimatoprost in sustained delivery devices ForSight Vision5 is developing an ocular insert to allow for continuous administration of bimatoprost for up to 6 months. Dubbed Helios, the insert is constructed as a polymer/bi- matoprost matrix in a soft, compli- ant ring about 26 mm in diameter. The ring is applied to the ocular surface in the clinic and maintained under the eyelids, according to the company. At 6 months, there was a mean diurnal IOP reduction of 4.7– 6.5 mm Hg from washout with no unexpected safety events. 1 A phase 2 study (n=130) was designed to deter- mine if the insert is non-inferior to timolol 0.5%. Results presented last year found over a 6-month period, the single dose of the bimatoprost insert (OU) lowered IOP by an average of 1 less mm Hg than the 360 drops of timolol applied to each eye in the other arm of the study. 2 A phase 3 study is expected to start this year. Allergan is developing bimato- prost SR, where "the amount of drug that's in one of those implants is the equivalent of one drop of agreed. With most patients on 2 different agents, delivering the drug subconjunctivally or intraoc- ularly not only reduces reliance on patients to comply with instillation, but removes the preservative (and the toxicity associated with it), as well as topical allergies or irritation associated with eye drops. Glaucoma delivery systems in the future When it comes to sustained delivery devices, Dr. Quigley said the device material is as important as the drug it's delivering. "Whatever is being placed into the vitreous or anterior chamber has the potential to damage the corneal endothelium or to block outflow. It has to dissipate entirely and do so benignly," he said. With 7 prostaglandin drug delivery systems in clinical develop- ment, how they deliver the drug is going to become more than just a marketing issue, said Gary Novack, PhD, PharmaLogic Development, San Rafael, California. "These are not devices—for regulatory purpos- es, that's a mandatory distinction from true devices. These deliver drugs and will be regulated as such." Currently, companies inves- tigating drug delivery systems for the treatment of glaucoma include Mati Therapeutics (Austin, Texas), ForSight Vision5 (Menlo Park, Cali- fornia), Graybug (Baltimore), Ocular Therapeutix (Bedford, Massachu- setts), Peregrine Ophthalmic (Singa- pore), Envisia Therapeutics (Mor- risville, North Carolina), Allergan (Dublin), and Glaukos (Laguna Hills, California). Two of these companies, Allergan and ForSight Vision5, are developing delivery systems with bimatoprost as the active ingredient. Down the road, companies will likely only continue to develop products that are potentially cost-ef- fective, Dr. Quigley said—and that means injections have to be quick and easy to deliver, and delivery sys- tems have to be comfortable enough for patients to continue to use them. With so many companies devel- oping these systems, all in different stages of development, "it's hard The expanding options will help glaucoma specialists manage patients' IOP better F or years, the mainstay of glaucoma treatment has been topical eye drops, laser angle treatment, and surgery (trabeculectomy, mostly) when patients can no longer be medically managed. But in the past few years, re- searchers and companies have begun to explore how to deliver intraocular pressure (IOP)-lowering drugs with sustained delivery systems. The ma- jority of drug delivery system studies are in their infancy, and it's not yet clear which devices will be success- ful. "In considering whether sus- tained delivery will make an impact, it's vital that they are applicable to the vast majority of glaucoma pa- tients. Otherwise, the development cost won't be worth it," said Harry Quigley, MD, director, Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University, Baltimore. And there are pros and cons to delivering the drugs on the surface of the eye or into the anteri- or chamber. Devices on the external part of the eye—such as punctal plugs— may not be obvious to the patient, and that means patients may not notice if they've fallen out. Others, such as contact lenses, are more eas- ily monitored for retention by the patient, but could be uncomfortable. Delivering drugs internally— either through an implant or via an injection—means that patients "will almost invariably have tem- porarily blurred vision, either from the implant itself, the drug, or from the process of prepping and inject- ing the eye," Dr. Quigley said. And injections run a potential risk of endophthalmitis. Put simply, "sustained-release is at the top of our wish list to improve patient compliance," said E. Randy Craven, MD, Wilmer Eye Institute. Sustained delivery instanta- neously improves the efficacy of any glaucoma drug because of that increased adherence, Dr. Quigley Drug delivery systems for glaucoma Bimatoprost SR in the anterior chamber Source: Allergan Device focus

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