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Alternative drug delivery platforms for glaucoma are coming
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Several alternative drug delivery systems to treat glaucoma are currently in the developmental pipeline and could be FDA approved soon.
There is a clear need for alternative glaucoma drug delivery systems to improve medication adherence rates in patients. According to a 2015 study published in Ophthalmology, more than 50% of glaucoma patients are non-adherent with their eye drop medications.
“The problem we face is that our patients don’t reliably take their medications. We do have a paradox, where we have very good treatments for glaucoma, but all of the studies that have monitored patients indicate that only half of the doses we prescribe get taken,” James D. Brandt, MD, director of glaucoma service at Tschannen Eye Institute at the University of California, Davis, told Ocular Surgery News.
Sustained-release platforms, whether as part of an external or internal delivery system, are a necessity to improve glaucoma medication adherence. The platforms must properly balance efficacy and duration with safety, ease of use, reversibility and other factors to be effective solutions for glaucoma patients, Brandt said.
All of the proposed systems have the goal of taking “patients out of the loop” from having to remember to take a drop one to three times per day for several months or the rest of their lives, Brandt said.
“There are a variety of approaches, including external devices that sit outside the eyes in the form of a contact lens or the form of a device that sits in the nasolacrimal punctum or a ring of polymer. The ring technology has been acquired by Allergan, a bimatoprost ring that is an external device that sits in the cul-de-sac and delivers drugs sustainably for 3 to 6 months or so at a time,” Brandt said.
Several companies have products in the pipeline that would involve a minor surgical procedure to inject sustained-release platforms directly into the eye. These platforms involve either a pellet that dissolves or a reservoir that could be replaced to deliver medications sustainably for weeks or months, Brandt said.
Allergan has two systems in development. Bimatoprost SR is a biodegradable implant in which an erodible pellet is injected into the anterior chamber during an office procedure. The pellet releases medication continuously for at least 6 months and is currently in a phase 3 clinical trial. The Bimatoprost Ring is a periocular ring for the conjunctival cul-de-sac that releases the drug over a sustained period of time.
The iDose (Glaukos) is a non-degradable titanium implant for the anterior chamber that contains a 6-plus month supply of travoprost and is also in a phase 3 trial.
Two companies currently have punctal plug systems in development. OTX-TP from Ocular Therapeutix is an erodible travoprost implant currently in a phase 3 clinical trial. The Evolute from Mati Therapeutics is a sustained ocular drug delivery platform wherein a punctal plug is inserted into the patient’s tear duct. The system is in a phase 2 trial.
All of these platforms could feasibly see commercialization in the next 3 to 5 years, Brandt said.
“The Bimatoprost SR platform will probably be approved first because it’s the furthest along. I suspect it will face the highest level of scrutiny by the FDA because the FDA is very aware of safety concerns with injectable platforms being used in people with mild diseases. There will have to be a balance of efficacy vs. safety concerns that the FDA and its advisory panels will have to consider,” he said.
Several cautions must be considered with these platforms, Brandt said. Prostaglandins are the most potent glaucoma treatment drug and are being used in these alternative delivery platforms, but not every patient can tolerate them. Additionally, few patients need only one glaucoma medication to reach their targeted IOP level. According to the results of the Ocular Hypertension Treatment Study in 2010, about 50% of patients required two or more medications to reach a modest 20% IOP decrease target, he said.
“We need to be very careful to not overpromise and overhype to our glaucoma patients that you could just put this delivery platform in and never use drops again. That’s simply not the case. Until we have sustained-release products that can deliver multiple drugs, each of which will have its own pharmacokinetics, it will be very challenging to deliver a drop-free life to our patients,” Brandt said.
Patients with relatively mild glaucoma are unlikely to be blinded or have significant visual impairment due to the disease. It is probably unwise to subject those patients to eye injections or put them at risk for corneal complications or infectious complications resulting from a platform procedure, he said.
“On the other hand, in someone with advanced disease who needs low pressures, where they can’t handle their medications, they can be a candidate for somewhat more risky interventions, such as injections into the eye, and may be a more reasonable choice for this treatment,” Brandt said. – by Robert Linnehan
- References:
- Brandt JD. Alternative drug delivery systems. How close to prime time? Presented at: AAO Subspecialty Day; Oct. 26-27, 2018; Chicago.
- Kass MA, et al. Arch Ophthalmol. 2010;doi:10.1001/archophthalmol.2010.20.
- Newman-Casey PA, et al. Ophthalmology. 2015;doi:10.1016/j.ophtha.2015.06.039.
- Nordstrom BL, et al. Am J Ophthalmol. 2005;doi:10.1016/j.ajo.2005.04.051.
- For more information:
- James D. Brandt, MD, can be reached at UC Davis Eye Center, 4860 Y St., Suite 2400, Sacramento, CA 95817-2307; email: jdbrandt@ucdavis.edu.
Disclosure: Brandt reports he owns stock with Glaukos; is a consultant for Aerie Pharmaceuticals; has a consulting relationship with Allergan; and is involved as the principle investigator with the phase 2 study for the Bimatoprost SR Ring when it was developed by the startup company ForSight Vision.