Long-term implant showing potential in glaucoma therapy

Reviewed by Tom R. Walters, MD

Take-home message: By administering biannual combinations of small and large pellets of ENV515, researchers are finding a possible alternative to topical therapy for lowering IOP.

Austin, TX-An extended-release therapy that encapsulates travoprost in an intracameral implant showed a statistically significant and clinically meaningful reduction in IOP with results comparable to topical once-daily travoprost ophthalmic solution, said Tom R. Walters, MD, Texan Eye, Austin.

Developer Envisia used particle replication in non-wetting templates (PRINT) technology to create its proprietary and fully biodegradable implant designed to elute a drug for up to 6 months. Its first product, ENV515, is under evaluation for the treatment of glaucoma

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“The PRINT technology has a lot of capability for sizing and shape that helps to determine how to best place this into the eye so that it is well-tolerated by the eye,” said Dr. Walters, who was an investigator for Envisia on these studies. The templates can be manufactured so that the end product eludes and dissolves at a very reproducible rate, he added. Early studies on hypertensive beagles found a rapid drop in pressure was maintained over 8 months.

“That’s a quite remarkable feat,” Dr. Walters said. “It means we were able to make the product so that it’s able to hold on to the therapeutic agent as it dissolves. There was no evidence of the pharmaceutical agent leaching out of the material prematurely.”

A phase IIa study enrolled 21 human patients with glaucoma and concurrent cataract who were being scheduled for cataract surgery. In a novel trial design, the ENV515 was placed at the time of cataract surgery and then purposefully removed after 4 weeks to assess efficacy implant status and determine efficacy and safety parameters.

Often with biodegradable products, studies will evaluate performance but do not plan on removal. “We wanted to see how the pellet was tolerated, see what the effect of pressure-lowering was after 4 weeks, but also be able to extract that product and examine it to determine how it is eluding the pharmaceutical product,” Dr. Walters said, adding the company also evaluated the pellet’s size and weight to determine if it swelled or absorbed during implantation.

“It helps us to design future iterations for longer-term studies,” he said.

About the trial

The ENV515 phase IIa multicenter clinical trial was designed as an open-label, 28-day dose-ranging study that enrolled 21 glaucoma patients at U.S. sites to assess the initial efficacy and tolerability of ENV515. Doses ranged from one small pellet to a combination of small and large pellets, Dr. Walters said. “We needed to determine what was going to be required to give us the efficacy we wanted. We got some extremely good results.”

ENV515, administered as a single pellet dose, achieved its primary efficacy endpoint, change from baseline in diurnal IOP at Day 25, by identifying a dose group (-6.7 mm Hg or -28%, p<0.001, n = 10) that is comparable to once-daily travoprost ophthalmic solution (-6.6 mm Hg or -28%, n = 21), administered to the non-study eye. The most common adverse event was early-onset transient hyperemia related to the dosing procedure.

Dr. Walters noted these results were for the single implant dose, but that results were better than expected in some combinations. For example, two small pellets produced better IOP-lowering than twice-daily timolol (which was used in the comparator eye).

“It’s reasonable to say that with one of the products, we’re easily getting something like the effect you’d expect with timolol twice-daily, and with two products, we’re getting an effect that’s similar to travoprost once-daily,” he said. “But with this product, it’s a one-time insertion instead of topical therapy.”

As might be expected, there was a significant reduction in topical side effects.

“The best thing we found from the patients is that they didn’t recognize the implant was there,” he said. “Physicians can use the slit lamp to ensure proper placement of the implant.”

New study

Dr. Walters added that a new study will include a 3-month endpoint with a 9-month safety rollout.

Those results will “allow us to confirm what we suspect about elution and when the pharmaceutical product stops working,” Dr. Walters said. “We’ll get 3 months of safety and efficacy and then, it will be just a safety evaluation to see how the product eventually stops working. We’ll evaluate the dissolution rate, as the product has only been in humans for 4 weeks.”

With so many patients having compliance issues, Dr. Walters is hopeful that if ENV515 is successful in its pivotal trials, these issues will be eliminated down the road.

“If we can get 6 or more months of efficacy, glaucoma may become an easier-to-manage disease,” he said. “Patients come in twice yearly, get a pellet, and no longer have to be concerned with compliance. Glaucoma specialists will no longer need to be concerned about the diurnal response of topical therapy. Just imagine how this is would improve glaucoma care in both developed and in third-world countries.”

Tom R. Walters, MD

E: tom@nobhill.me

This article was adapted from Dr. Walters’ presentation at the 2015 meeting of the American Academy of Ophthalmology meeting. Dr. Walters is an investigator for Envisia.