Travoprost implant maintains IOP-lowering benefit at 11 months

New data from a phase IIa study show that an investigational intracameral extended-release travoprost implant (ENV515, Envisia Therapeutics) provided durable IOP-lowering over a follow-up period extending to 11 months.

Results showed that the IOP-lowering effect in eyes receiving a low-dose version of the extended release implant (ENV515-3) matched that associated with use of topical prostaglandin analogues prior to study entry and was comparable to that achieved in the study at 11 months in fellow eyes being treated with twice daily timolol maleate 0.5% as a control.

“ENV515 was designed to address an unmet need in glaucoma regarding poor adherence to topical treatment,” said Thomas Walters, MD, study investigator and medical director, Keystone Research, Austin, TX. “Current data from the phase IIa study indicate the product has the potential to provide a 12-month duration of action after a single dose.”

Studying optimized version

Currently, an optimized version of ENV515 (ENV515-3-2) that has the potential for longer duration than the current low dose product is being studied in an ongoing phase IIa study, he noted.

ENV515 is an extended-release travoprost formulation developed to be administered by the physician in a simple, in-office procedure. It uses a biodegradable polymer drug delivery system and was designed with the aims of both having a constant release profile over a duration exceeding 6 months and causing less hyperemia than topically administered prostaglandin analogues, Dr. Walters said.

The phase IIa clinical trial program is comprised of three patient cohorts and intends to optimize the product design. The first cohort included 21 patients with glaucoma being treated with a topical prostaglandin analogue who were scheduled for cataract surgery. About 4 weeks before cataract surgery and after washout of existing treatment, ENV515-3 was implanted in the surgical eye and patients began using topical travaprost 0.004% (Travatan Z, Alcon Laboratories) in the fellow eye.

Findings from serial follow-up visits showed ENV515-3 lowered IOP comparably to topical travoprost. Sampling of aqueous humor at the time of cataract surgery showed that the comparable treatment effect of ENV515-3 was achieved with a travoprost concentration in the anterior chamber that was about 19-fold lower than the historically reported level occurring at 3 hours after topical travoprost 0.004% administration.

The second cohort in the phase IIa program enrolled five patients who also received ENV515-3 after undergoing washout of preexisting treatment with a prostaglandin analogue. During the study, patients used timolol maleate 0.5% twice daily in the fellow eye.

At study entry before washout of existing prostaglandin analogue therapy, mean IOP at 8 AM was 19.7 mmHg in eyes that would receive ENV515-3 and 19.3 mmHg in the fellow control eyes. Mean baseline IOP (post-prostaglandin analogue washout) at 8 AM was 26.1 mmHg in both eyes. At 11 months after ENV515-3 implantation, mean change from baseline IOP was -6.7 mm Hg in the ENV515-3 eyes and -7.1 mm Hg in the timolol eyes.

“Analyses of the diurnal IOP treatment effect showed it was maintained over the measured diurnal cycle for 11 months after a single low dose of extended-release travoprost,” Dr. Walters said.

Safety analysis

The safety analysis showed there were no serious adverse events in eyes implanted with ENV515-3. The majority of recorded ocular adverse events occurred early in the study and were primarily related to the dosing procedure and particularly to the topical povidone-iodine that was used for sterile preparation.

Analyses of hyperemia scores recorded at monthly follow-up visits showed that the product also seemed to achieve the intended goal of minimizing this adverse event.

“For a majority of the duration of action, ENV515-3 induced hyperemia that was either no different from baseline severity or below the level induced by the topical prostaglandin analogues used prior to study entry,” Dr. Walters said.

Dr. Walters is a consultant to Envisia Therapeutics.