There’s a certain irony to Amorphex Therapeutics working in the dark basement of a 100-year-old Andover mill building.
“It’s atrocious, but classic,” president and CEO Robert Thompson laughs, trying to explain the peculiarity of scientists working on cutting-edge ophthalmic technology in an antiquated former mill complex.
“We don’t have luxurious office quarters, but we do have about 1,000 square-feet: A clean room to bottle solutions, a machine to measure viscosity, and a full laboratory,” explains Dr. Charles Leahy, Amorphex’s vice president of medical affairs and lead scientist for Amorphex sister firm Vista Scientific. “It’s unassuming on the outside, but effective and efficient on the inside.”
That’s an apt description for the products Leahy, Thompson and business partner Dr. Edward Ellis are developing to break into the $12 billion global ophthalmic pharmaceuticals market, Amorphex’s Topical Ophthalmic Drug Delivery Device and Vista’s nanosphere contact lens.
The lenses are designed to distribute medication into a patient’s infected or diseased eye in the most effective way possible, supplanting periodic eye injections or eye drops as the delivery vehicle.
Treatment of back-of-the-eye conditions like macular degeneration (the most common cause of blindness in the United States in patients age 50 and over) or diabetic retinopathy typically involve periodic injections into the center of the eye.
For front-of-the-eye conditions such as glaucoma, conjunctivitis and dry eye, eye drops are the most common treatment. But they aren’t the most effective method of delivering medication, Thompson says, because at most about 7 percent of an eye drop’s drug actually reaches its target.
“Eye drops are probably the poorest method of putting medication in the eye, mainly because of the tears that kick in as a response to an object going into the eye,” explains Ellis, Vista’s vice president of science and technology. “So the medicine can get washed out in about 15 minutes.”
That excess medicine may not penetrate the eye quickly enough to be effective, Thompson and Ellis note. And the difficulty of trying to precisely land a drop into a blinking eye doesn’t help either.
{IMAGELEFT:http://www.massdevice.com/sites/default/wp-content/uploads/headshots/Leahy_Charles_100x100.jpg}”Think about it this way: Someone just go out of cataract surgery, they only have one good eye, and you’re asking them to put tiny drops in their other eye,” says Leahy, a clinical instructor in ophthalmology at Harvard Medical School. “For some serious infections, you’re telling folks to put in drops three or four times a day or even every hour or two. Some patients have to get up in the night to put a drop in, maybe for just the first two days, but who wants to do that?”
Thompson says these challenges, along with people’s tendency to stop taking medication once they feel better — but before it’s done its work — has led to a low compliance rate. Greenstein and Thompson say compliance is especially problematic among glaucoma patients; as few as 54 percent continue to take their medication through the entire course of treatment.
“The issue, especially with glaucoma, is the patient doesn’t feel bad, doesn’t feel any symptoms, but day-by-day your visual capabilities are degrading. Your eyesight narrows and narrows until you go blind,” says Thompson.
There is no cure for glaucoma. Patients are required to take eye medication for the rest of their lives.
That means ophthalmic drug delivery is a growing business, fueled in the past few years by efforts to prevent blindness in a rapidly expanding elderly population. The global ophthalmic pharmaceutical market in general is expected to grow 11.1 percent per year until 2012; glaucoma therapies alone are expected to make up more than 40 percent of that market, according to Visiongain.
“In the field of glaucoma there’s a ton of interest for someone to come up with a better method of taking eye medication,” Thompson says.
{IMAGELEFT:http://www.massdevice.com/sites/default/wp-content/uploads/featureArt/TODDD_100.jpg}Amorphex’s Topical Ophthalmic Drug Delivery Device is designed with just that in mind. The device, which sits on the eye’s white sclera, resembles a miniature, clear sleeping mask. Inside, a combination of materials created by Ellis and Leahy controls the release of medication.
But wearing a sclera lens can feel like having a piece of lumber under your eyelid; Thompson says the Amorphex device avoids these problems, because it’s thin and soft, lies flat on the sclera and is held in place by the upper eyelid.
“The needed drug then slowly migrates to the surface of the eye. It is released over 90 days primarily through the cornea, so it doesn’t affect vision, but it gets absorbed through all of the tissue in the front of the eye,” he says.
According to Thompson, glaucoma patients would receive a new device when they see their eye doctor, typically every three months.
Amorphex has patents for the device and the polymer it’s made of and has completed a round of animal safety studies, but the product could still be a few years from hitting the market.
“Our rabbit testing confirmed that TODDD did lower intra-ocular pressure, which is what an eye doctor wants in order to better manage glaucoma,” Thompson notes. “We’ll probably have to tweak manufacturing the size of product, and then its release depends on FDA requirements.”
In addition to the drug delivery device, Ellis and Leahy have been busy in the Vista Scientific lab creating a contact lens made using nanospheres they’re calling Theralens.
“There have always been efforts to put drugs into the eye in new ways, like contact lenses for example, but there have always been physical limitations,” says Leahy, who runs the contact lens service department at the Massachusetts Eye and Ear Infirmary.
According to Leahy, the challenge of perfecting a medicated lens lies in preventing it from releasing its drug too quickly over the eye’s large surface area. The lens must also be the right thickness and shape to precisely — and comfortably — fit the cornea, while allowing oxygen to pass through to the cornea.
“You have certain parameters you must stick to — oxygen permeability, shape, and surface clarity — and try to apply all of that to eye medication,” Leahy explains.
“Finding the material for a contact lens isn’t so difficult,” Ellis adds. “A commercially available soft contact lens is made up of 50 percent water. It’s the shape, the thin membrane and the optics that can be difficult.”
He and Leahy have gotten around most of those obstacles for now by testing a conventional hydrogel formula used by companies such as Bausch & Lomb for contact lenses. Engineering the slow, effective dispensation of small amounts of medicine from a thin lens was the tricky part.
“We didn’t need to change the make-up of the lens. So, instead of changing the batter of the cookie mix, we added the chips — which is the nanosphere,” Leahy says.
“Nanoparticles are smaller than a wavelength of light,” explains Ellis. “So the idea is to develop a matrix of nanospheres that can be put into a lens. They will be clear because the nanospheres are very small, but they will be able to hold the medicine and control its disbursement.”
Stephen McCarthy, director of the Massachusetts Medical Device Development Center at UMass-Lowell, says the Vista Scientific nanosphere is made of elements that both like and dislike water. The half that dislikes water, a biodegradable chemical, caprolactone, bonds with the eye medication. A starchy substance called pullulan wraps around the outside of the drug-caprolactone mixture.
“The drug molecules used to treat diseases, such as the antibiotics needed after cataract surgery, can go into this nanosphere,” Leahy says.
“We dissolve everything in a solution that’s 50 percent solvent and 50 percent water. We keep adding water until we have a pure water mixture,” McCarthy says. “The pullulan and caprolactone suspend the medication in the water, but prevent it from dripping out all at once. Then we can place this combination in the contact lens, which is predominately water.”
Once on the eye, the medication gradually spreads out of the nanosphere both on its own and as the nanosphere degrades.
The main differences between the nanosphere lens and the Amorphex device involve product size and placement. Because it covers only the sclera, Leahy explains, the latter doesn’t have to allow oxygen through to the cornea or pupil. This gives it more volume to take on more medication.
“We’re also just still in the development stage for the nanosphere product,” Ellis says. “We’re hoping to produce the contact lens material ourselves. If we get a Phase Two grant, we can produce the actual lens. However, if we perfect the nanosphere first, we might approach one of the big companies to see if they’ll produce the lens we need.”
{IMAGELEFT:http://www.massdevice.com/sites/default/wp-content/uploads/headshots/Greenstein_Scott_100x100.jpg}Scott Greenstein, a cataract surgeon at the Massachusetts Eye and Ear Infirmary and a clinical instructor in ophthalmology at Harvard Medical School, says the twin companies’ products hold promise for ophthalmic patients, but the group may face other challenges on the marketplace.
“For glaucoma patients who have to take drops two, three or four times a day, they might be better served with a product in the eye,” he says, “but a sclera lens can be extremely uncomfortable. I’d be concerned about how well a lens like that would be tolerated.
“I’m positive on these ideas, but I don’t see them being used as a routine measure. However, they would be best for chronic eye conditions that would require constant applications of medicine, and maybe for those with arthritis, who have trouble with their fingers. I have patients who can’t remove a cap from the bottle and squeeze the bottle, so they could be helpful there.”
Thompson, Leahy and Ellis say they’re confident they’ll find a market for technology that makes applying eye medication as easy as putting on a Band-Aid, secure in the belief that the lenses taking shape in that dark Andover basement could end up bringing light into thousands of patients’ eyes.