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Five patients receiving an extended-release travoprost delivery system (ENV515, Envisia Therapeutics) in the anterior chamber have ongoing IOP-lowering with follow-up to 9 months in an ongoing study.
Reviewed by Thomas Walters, MD
An extended-release intracameral implant loaded with travoprost (travoprost XR; ENV515, Envisia Therapeutics) was found to be well tolerated and effective for providing sustained IOP-lowering, according to 9-month interim analysis findings in an ongoing phase II trial.
The study included 5 patients with bilateral ocular hypertension or open-angle glaucoma previously treated with a topical prostaglandin analogue (PGA). They received a single dose of a low-dose formulation of the travoprost XR implant in one eye and used topical timolol maleate ophthalmic solution 0.5% contralaterally, twice daily.
In October 2016, Envisia Therapeutics announced that in an interim analysis, the investigational product provided clinically meaningful reduction in IOP throughout 9 months of follow-up.
The magnitude of the effect was comparable to that achieved prior to the study with topical prostaglandin treatment and during the study with topical timolol treatment in the fellow eye of the same patients.
Anecdotally, the IOP-lowering effect with the travoprost intracameral implant has been maintained beyond the 9-month assessment and without loss of clinical efficacy, noted Thomas Walters, MD, study investigator and medical director, Keystone Research, Austin, TX.
“The ongoing efficacy of this intracameral implant is quite remarkable, and safety data indicate that it minimizes or avoids several of the side effects associated with the topical administration of a prostaglandin,” he said. “Namely, hyperemia seems to be reduced compared to daily topical PGA therapy.
“The experience is still very preliminary, but suggests this product has the potential to be a big game-changer in medical therapy for ocular hypertension and glaucoma by taking patient compliance with daily drops out of the equation,” he added.
Prior to washout of existing IOP-lowering medications, the 5 patients included in the study were using topical latanoprost 0.005% or travoprost 0.004%. Their mean IOP measured at 8 a.m. while on pre-study medication was 19.7 mm Hg and was 26.1 mm Hg after washout.
The travoprost XR implant was already observed to have an IOP-lowering effect when the first measurement was taken on Day 3. At 9 months, mean IOP was reduced by 6.7 ± 3.8 mm Hg (-26%) from the post-washout level.
“Because of the steady release of travoprost from the delivery system, the intracameral implant also controls diurnal fluctuations in IOP better than topical therapy,” Dr. Walters said.
Dr. Walters noted there is some anterior chamber inflammation for about 2 days after the implantation procedure, which is due in part to the use of povidone-iodine for sterile preparation.
“After that resolves, the eyes have been very white and the anterior chamber quiet,” he said. “Problems that patients had in association with topical prostaglandin use prestudy, such as blurred vision and conjunctival hyperemia, largely abated.”
The procedure for placing the intracameral implant is easily done under topical anesthesia. In addition to the povidone-iodine preparation, the lashes and lids are isolated with a speculum and a surgical drape placed.
Placement of the implant is similar to inserting a paracentesis port. The device is introduced into the anterior chamber in front of the iris and settles itself down into the inferior angle. The biodegradable device is rectilinear in shape, but becomes more amorphous and conforms to the angle as it dissolves over time, Dr. Walters said.
Monitoring is ongoing to determine the longevity of the IOP-lowering benefit, although variation among patients is expected considering the potential for the kinetics of the implant’s degradation to differ in the eyes of different patients.
A third cohort of the ongoing clinical trial investigating the travoprost XR implant was recently launched in which a high dose of ENV515 is being studied with the expectation of providing an IOP-lowering treatment effect that will extend beyond 12 months after a single dose.
“In patients, the low dose demonstrated 9 months of IOP lowering efficacy after a single dose,” Dr. Walters said. “The high dose demonstrated 3-month-longer IOP duration versus the low dose in preclinical evaluations in Beagle dogs, thus, supporting its potential for once-a-year therapy.”
Thomas Walters, MD
Dr. Walters is an investigator and consultant for Envisia Therapeutics and multiple other companies with products for IOP lowering.