Don’t blame ineffective drugs for failures to control IOP. Patients play a major role.
“The problem is not that the medications don’t work, but that patients don’t put the drops in,” said Eugene de Juan, Jr., MD, founder and vice chairman of ForSight Labs. “Even if we came up with the perfect drop that would prevent any progression of glaucoma, it would still only work in half the population. Half of patients just don’t use their medications.”
Dr. de Juan introduced drug-delivery companies that promise to change that discouraging picture. A new generation of drug-delivery devices promise to automate dosing for 100 percent adherence. But to pass that bar, this new generation of devices must be preferred by patients over drops, satisfy clinicians that they at least equal the efficacy of drops, must be persistent in effect, and must have a clear reimbursement pathway.
“I see drug delivery not as a convenience, but a necessity for the effective treatment of glaucoma,” Dr. de Juan said. “This is the practical goal of drug delivery.”
Here is a round-up of companies developing drug-delivery devices, which presented during the New Horizons in Glaucoma Delivery session:
The TODD (Topical Ophthalmic Drug-Delivery Device) is a soft elastomeric structure that floats atop the sclera under the eyelid. It can be handled as easily as a contact lens and a single insertion ensures steady state drug delivery from three to more than 90 days.
“We are delivering therapeutic amounts of drug, but unlike drops, we are not getting any drug in plasma,” said Robert Thompson, president and CEO. “Imagine timolol without the cardiovascular side effects but with all the therapeutic effects on glaucoma.”
TODD can elute drug, release drug from multiple reservoirs or do both to deliver multiple drugs. If the device is in place, the patient is getting the programmed dose.
The suprachoroidal space is not a drug-delivery target. A new microinjection platform could change that.
“You can put a very large amount of drug into the suprachoroidal space,” said CEO Daniel White. “Drug spreads around the posterior pole of the eye. We have established a new dosable space.”
Suprachoroidal dosing ensures high bioavailability to the blood-retinal barrier, White said, which helps target posterior inflammation and choroidal neovascularization. Localizing drug in the posterior segment also improves safety profiles.
In trials with Avastin, only one of 27 patients showed a transient IOP increase over 21 mm Hg. There were no cataract surgeries, no glaucoma surgeries and no suprachoroidal hemorrhages.
Timed drug release is a familiar strategy. Euclid has engineered two collagen-based devices that provide sustained release of latanoprost for glaucoma.
“Collagen is a very safe implant material, very well known to the FDA,” said Dale DeVore, PhD, chief scientific officer. “We can manipulate it into different physical forms with controlled bioabsorption kinetics.”
One formulation is injected as a viscous fluid to form either a gel or a fibrous matrix. The other is implanted as a biodegradable wafer that degrades over minutes to six months and longer. Preliminary rabbit studies showed no significant insertion issues and tissue reactivity was limited to minor conjunctival congesting and hyperemia at the implant site.
“If you can get the right drug to the right place in a safe and simple manner, you can address many conditions,” said CEO William White. “The problem is not with the agents, it’s the patients.”
Icon sidesteps patient adherence with a new dosage form. Verisome delivers familiar agents, such as timolol and latanoprost, as a liquid sphere in the aqueous humor. Controlled bioabsorption delivers the appropriate drug dose with no patient action needed.
The clinician can monitor delivery simply by looking into the eye, White said. If the Verisome is visible, drug is being delivered. Remaining drug can be removed with simple needle aspiration if needed.
The physical properties of microscopic drug particles delivered in eye can have dramatic effects on therapeutic activity. Liquidia has adapted micron-scale lithographic techniques from electronic circuit manufacturing to pharmaceuticals. The result is precisely designed drug particles with specific physical shapes and biochemical attributes for more closely controlled biologic activity.
“We can give you straight-line particle distribution, not a Gaussian distribution,” said Benjamin Yerxa, PhD, chief science officer. “We can give you pollen-like propeller shapes, rods, spheres, cubes, donuts, boomerangs, with precise stiffness and porosity and surface chemistry. We can vastly improve the solubility of compounds like cyclosporine, tachrolimus, and steroids or design agents for intracellular absorption.”
Hydrogel drug delivery is nothing new-except in the world of ophthalmology. Ocular Therpeutix is adapting hydrogels to three distinct platforms, reported CEO Amar Sawhney.
One is a bioabsorbable drug-eluting punctum plug for glaucoma. Another is a hydrogel drug depot for intravitreal delivery of anti-VEGF agents with sustained release up to six months.
Mitomycin is one of the most widely used ophthalmic medications that has never been approved for ophthalmic use.
“The use of mitomycin C is ubiquitous in ophthalmic applications, but there are problems throughout the supply chain,” said Ed Timm, President and CEO. “We are solving those problems for all parties.”
The new Mitosol injection kit has a shelf life of 24 months at room temperature, provides NIOSH-compliant disposal, and does not carry a black box warning. Medicare Part B coverage became effective in April 2013.
“The cost of Mitosol will come from the third party payer,” Timm said. “If you continue with a compounded mitomycin, the cost will have to be harvested from the facility.
‘I see drug delivery not as a convenience, but a necessity for the effective treatment of glaucoma.’
Eugene de Juan, Jr., MD