Innovation in glaucoma thriving

By Fred Gebhart

Innovation in glaucoma diagnosis and treatment is alive, well­–and profitable. That was the upbeat report from Emmett Cunningham, Jr., MD, PhD, MPH, ophthalmologist and partner with venture capital firm Clarus Ventures, LLC. The glaucoma pharmaceutical sector alone is set to grow from $4 billion in 2013 to $5 billion by 2018.

Emmett Cunningham, Jr., MD, PhD, MPH, said the glaucoma pharmaceutical sector alone is set to grow from $4 billion in 2013 to $5 billion by 2018. (Photo by Stevan Nordstrom)

“The glaucoma market is growing very nicely,” Dr. Cunningham said. “We are not seeing any slowing of innovation in glaucoma.”

The biggest news for 2013 was the approval of Alcon Laboratories’ combination drug of brinzolamide and brimonidine. Simbrinza is the first fixed-dose, combination glaucoma agent without a beta-blocker to be approved for the U.S. market. The net IOP lowering achieved with Simbrinza at various time points suggests FDA flexibility regarding approval thresholds.

 “Alcon managed to lower the IOP hurdle without compromising safety, especially systemic safety,” he added.

The drug pipeline is equally promising. Amakem Therapeutics presented early clinical results for AMA0076, a topical Rho Kinase inhibitor (ROCKi) with activity confined to the anterior chamber. Seven-day data in normotensive eyes showed, what Dr. Cunningham called, a “very nice” IOP-lowering effect that is greater than reductions usually seen in normotensive eyes. And, because activity is localized, there appeared to be less redness than has been seen with other ROCKi agents.

The biggest pipeline news is AR-13324, a combination ROCKi and norepinephrine transport inhibitor (NETi) from Aerie Pharmaceuticals. The ROCKi facilitates outflow while the NETi decreases aqueous production.

Phase IIb data for a full cohort of 221 eyes with once-daily dosing showed IOP lowering that is about <1 mm Hg than latanoprost. But a subgroup analysis of patients with a baseline IOP of between 22 mm Hg to 26 mm Hg showed clinically and statistically equivalent lowering of IOP, compared to latanoprost at 14 days and 28 days.

“That is an important finding because most glaucoma patients fall into that 22 mm Hg to 26 mm Hg range before treatment,” Dr. Cunningham said. “At the same time, the phase I pharmacokinetics study showed a 30% reduction in IOP for normotensive eyes, which is better than the IOP reduction seen with prostaglandins. The results suggest a novel mechanism of action.”

ROCKi agents act through the trabecular meshwork to facilitate outflow, but the precise mechanism is not entirely clear. It is known that outflow resistance is a major determinant of IOP. Outflow resistance is determined in large part by the episcleral venous pressure (EVP). EVP sets an effective floor for IOP, Dr. Cunningham explained, which suggests that Aerie’s ROCKi agent may act by reducing EVP.

“ROCKi agents hold major promise,” he said. “They offer significant IOP reduction through the range of pressures we see in practice, not just at the high end.”

Device world

Glaucoma devices are starting their own growth spiral. Glaucoma procedures account for about 5% of the 46 million ophthalmic procedures performed globally each year. Micro Invasive Glaucoma Surgery (MIGS) came on the scene in 2012 and are set to surpass traditional glaucoma surgeries by 2016.

Traditional shunt and filtering surgery numbers have been virtually flat the past two years, Dr. Cunningham said. Nearly all the growth in glaucoma procedures has come from MIGS.

“Glaukos founded the MIGS space in 2012 with the iStent,” he said. “In 2013, they did over $20 million in revenue, which is fantastic for a first full year on the market.”

Glaukos continues to grow, he continued, but the company won’t have the market to itself for long. Several competitors are moving through clinical development toward what they hope will be approval. The three leading contenders are Transcend Medical (CyPass Micro-Stent), AqueSys (XEN Glaucoma Implant), and Ivantis (Hydrus Microstent).

Drug delivery

Drug delivery is a weak point in glaucoma treatment. Eye drops work, but only if used properly. And adherence falls precipitously to well below 50% for most topical glaucoma agents within the first six months.

“Developing sustained-release drug delivery is important,” Dr. Cunningham said. “Punctal plugs have moved into phase II trials with latanoprost.”

What began as a 1.45-mm punctal plug from ForSight has moved to QLT to Matai Therapeutics. The initial design has been re-engineered so that the plug is better retained in the punctum.

Ocular Therapeutix is moving forward with its own punctal plug loaded with travoprost. The company plans to launch a 90-day phase IIb trial later this year.

Diagnostics

The latest development in diagnostics is devices for continuous monitoring. Two competing designs are moving through development.

Sensimed’s Triggerfish is an external device that provides continuous IOP measurement. Implandata Ophthalmic Products is developing a permanent device to be implanted during cataract surgery. IOP data are transmitted to an external unit, using an RFID-powered system originally used in automotive applications.

“These are both promising products, given that more data is always better,” Dr. Cunningham said. “The major unanswered question is who will pay for such data, and whether outcomes data will need to be generated to convince payers.”