ForSight is developing an ocular insert shaped like an O-ring that rests under the eyelid as it elutes drug. The latest phase II trial used a 6-month bimatoprost formulation. The insert is designed for removed and replaced for continuous dosing.
“Highly effective topical medications exist, but up to 60% of glaucoma patients cannot use their drops properly,” said James D. Brandt, MD, professor of ophthalmology and vision science and director of the Glaucoma Service, University of California, Davis. “We need a sustained-release, patient-independent method of delivery of medications. And we demonstrated that this novel, sustained-release delivery of bimatoprost can sustain clinically relevant doses for 6 months after a single application.”
The phase II trial compared the bimatoprost-eluting insert with twice-daily timolol drops. A total of 130 patients were randomized to either a drug-loaded insert and placebo drops or placebo insert and timolol drops. While both groups showed a similar 4- to 6- mm Hg drop in IOP after 6 months, the trial was not powered to demonstrate non-inferiority. A 6-month, phase III non-inferiority trial is planned for later in 2016.
About 90% of the inserts were retained and patients were aware of inserts that became dislodged. The inserts were extremely comfortable, Dr. Brandt reported.
“We would expect this insert to be used in patients who cannot or choose not to use topical medications,” he said. “This level of IOP lowering in highly relevant in this clinical realm.”
GrayBug is developing a microparticle technology created at the Wilmer Eye Institute/Johns Hopkins University School of Medicine.
“We have combined IOP lowering and neuroprotection in a single pro-drug compound that would be very effective dosed twice a year in treating glaucoma,” said Jeffrey L. Cleland, PhD, interim CEO. “You can’t have tradeoffs in drug delivery, you have to have safety. We have no inflammation and no histology out to 6 months after administration.”
The company is developing three glaucoma agents––a single IOP-lowering compound; a dual-action, IOP-lowering compound; and IOP-lowering plus neuroprotection. Administration is by injection, either intravitreal or subconjunctival for glaucoma. The particles are injected outside the visual axis, where they aggregate into a visible implant. The implant is resorbed completely over the 6-month course of dosing.
Dr. Cleland said the company has had useful discussions with the FDA and is moving toward its first IND. Clinical trials of an agent to treat wet age-related maculae degeneration (AMD) are expected to begin later in 2016.
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“Glaucoma has major challenges of compliance,” he said. “Converting people from drops to twice a year subconjunctival dosing would be quite attractive. We are working with a pro-drug approach using metabolites that are already used in the eye, which we believe will make a safe platform.”