Future of glaucoma medications

Within 10 years, a range of extended-release platforms that deliver glaucoma drugs to the eye for three-to-six months or more are likely to be available for clinical use, James D Brandt MD told the Glaucoma Subspecialty Day at the 2018 American Academy of Ophthalmology Annual Meeting in Chicago, USA. These may include intracameral and conjunctival implants, and drug-eluting punctal plugs and conjunctival rings, several of which are in or approaching phase III clinical trials. However, while such devices may improve intraocular pressure (IOP) control, they are not likely to eliminate eye drops for many patients, and some may not be suitable for treating early disease, said Dr Brandt, of the University of California, Davis, USA. Variable effectiveness among patients, delivering multiple medications and addressing potential complications are among issues that will take years of clinical experience to completely address, he added. ANTERIOR CHAMBER IMPLANTS Closest to market is the Bimatoprost SR (Allergan), a biodegradable implant injected into the anterior chamber designed to release medication for four months or more. Three-month data released in January from two 20-month phase III clinical studies now in progress suggest that the device reached its 12-week primary efficacy goal of non-inferiority to timolol drops for reducing IOP, and is as effective as topical prostaglandins. The studies also suggest the device may be effective for 12 months or more in most patients, according to an Allergan release. Travoprost XR-ENV 515 (Envisia Therapeutics) is a biodegradable implant delivering Travoprost over extended periods nearing the end of a phase IIa trial. Also in phase III trials is iDose (Glaukos), a non-biodegradable titanium anterior chamber implant anchored in the trabecular meshwork that releases travoprost for six months or more, and can be replaced periodically. In phase II trials it, too, showed similar efficacy to topical timolol and prostaglandins, reducing IOP by about 30% in open-angle glaucoma patients. Promising as these implants appear, the need for surgical implantation presents challenges, Dr Brandt noted. These include the need for a second surgery to remove them should the patient develop cystoid macular oedema or other complications, and the potential long-term effects of anterior chamber placement on the corneal endothelium. External devices may address some safety and reversibility issues. These include punctal plugs, such as the OTX-TP (Ocular Therapeutix), which supplies travoprost for up to 90 days and is in phase III trials, and Evolute (Mati Therapeutics), which delivers latanoprost and is in phase II trials. Dr Brandt has conducted extensive trials of the Bimatoprost Ring (Allergan), which is a periocular ring installed in the conjunctival cul-de-sac, releasing the drug for six months or more. In a phase II study followed by a 13-month open-label extension, the ring was effective in reducing IOP for 19 months with three insertions and was retained by 95% of patients over the last 13 months with a safety profile similar or better than topical treatment. THERAPEUTIC LIMITS However, while sustained-release glaucoma devices are on the horizon, for many patients they are not likely to completely meet their intended goal of eliminating eye drop use any time soon, Dr Brandt noted. In part that’s because about half of patients require more than one medication to adequately control IOP. Combining multiple drugs in a single device may be a solution. But developing these will take time and may be challenging due to differing pharmacokinetic properties of different medications possibly affecting their availability. Variations in length of time a device maintains therapeutic drug levels across populations will also need to be assessed and monitored closely to ensure patients do not run out prematurely. The risk of some devices, particularly implants, must be balanced against the benefits of topical medications, and the trade-off may favour drops for early-stage patients. Long-term observation under real-world conditions will be needed to evaluate these risks and this will take time, Dr Brandt said. “We need to be careful not to over-promise” that patients will never need drops again, he emphasised. James D Brandt: jdbrandt@ucdavis.edu