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Phase I/II interim data for a bimatoprost sustained-release implant show the device has favorable safety and efficacy and may address the problem of patient nonadherence.
Take-home message: Phase I/II interim data for a bimatoprost sustained-release implant show the device has favorable safety and efficacy and may address the problem of patient nonadherence.
Sacramento, CA-A sustained-release implant of bimatoprost was well tolerated and associated with a reduced incidence of prostaglandin analogue use in the first 6 months, according to a phase I/II study on the interim results.
Richard A. Lewis, MD, in private practice in Sacramento, CA, and colleagues evaluated the safety and IOP lowering effect of bimatoprost in a sustained-release depot.
“Nonadherence of patients to treatment regimens is endemic in chronic, asymptomatic diseases and is associated with worse outcomes and overall increased healthcare costs,” the authors wrote in their poster.
Glaucoma is often cited as one of many disease states in which patient noncompliance and nonadherence is prevalent, and both clinicians and patients may be able to benefit from a dosing regimen that reduces reliance upon the patient component.
In glaucoma, there are several potential barriers to adherence, including patient memory, difficulty with eye drop instillation or recalling the dosing frequency. If patients do not fully understand their disease, they may not appreciate how integral the topical medications are to their overall improvement, Dr. Lewis said.
Medication costs and potential side effects may also be responsible for intentional patient non-compliance.
In general, sustained-release therapy has the potential to overcome those issues while providing long-term IOP lowering without the need for topical instillation. Allergan developed a biodegradable bimatoprost sustained-release implant “to be placed intracamerally in the eye and provide slow release of bimatoprost over a period of 4 to 6 months,” the poster said.
This is an ongoing, prospective, 24-month, dose-ranging, paired eye, controlled phase I/II clinical trial (ClinicalTrials.gov NCT01157364), where phase I is open-label and phase II is masked. All enrolled patients (n = 75) underwent a washout from 4 to 28 days (depending on previous medication). On day 1, bimatoprost SR was administered intracamerally in the study eye in one of four doses: 6, 10, 15, or 20 ug Generation 2 formulation.
The fellow eye began treatment with topical bimatoprost 0.03% once daily (all subjects were requested to instill the fellow eye in the evening). Follow up was scheduled on days 2 and 8, weeks 2, 4, 6, 8, 12, 16, and 20, and then months 6, 7.5, 9, 10.5, and 12. The investigators used Goldmann applanation tonometry with all readings (masked) at 8 a.m. at all visits (considered Hour 0); other readings were taken at hours 2, 4, 6, and 8 at selected visits.
According to the study parameters, rescue therapy with topical IOP-lowering medications could be started in either eye if the eye failed to achieve the investigator’s target IOP on consecutive visits of more than 1 week apart. In the treated eye, a single repeat treatment with the implant was allowed between day 90 and month 12 if re-treatment criteria were met. That included no previous rescue therapy in either eye, a change in IOP in the study eye of more than 20% at the 8 a.m. reading at consecutive visits, and if the initial implant demonstrated adequate safety and did not contact the corneal endothelium.
The primary endpoint was the IOP change from baseline. Other outcome measures included the use of rescue medication.
At baseline, the mean age of the patients was 63.2 years (ranging from 21 to 83 years old), and there were 37 males (49.3%). The majority of patients were Caucasian (n = 53; 70.7%), and the iris color was fairly evenly split between dark (brown or dark brown, n = 40) and light eyes (any other color, n = 35). Baseline IOP after washout in the study eye was 25.2 mm Hg.
After intracameral injection, the bimatoprost SR “can be visualized in the inferior iridocorneal angle, where it slowly elutes the drug and biodegrades,” Dr. Lewis said.
In the first 12 weeks, there was a “rapid and sustained” IOP-lowering effect, and a dose response “was generally evident,” the authors said. “The magnitude of IOP reduction was typical of a topical ophthalmic prostaglandin.”
Mean IOP reduction through week 16 ranged from 7.2 to 9.5 mm Hg. The fellow eye averaged 8.4 mm Hg reduction on once-daily bimatoprost, the authors reported.
Rescue therapy was required in 4 study eyes (5.3%) through week 12 and in 6 study eyes (8%) through week 16.
Bimatoprost SR continued to provide “statistically significant (p < 0.001) and clinically signifiant IOP lowering through 6 months of follow-up. The majority of patients did not require rescue therapy or re-treatment with bimatoprost SR,” the authors said. At month 6, they said, 71% of eyes had not received rescue therapy nor a second injection of bimatoprost SR. IOP-lowering results were similar in all bimatoprost groups.
As expected, the most common ocular adverse event was conjunctival hyperemia, No serious ocular adverse events were noted in any study eye.
The interim positive results have led to the initiation of phase III studies.
Richard A. Lewis, MD
This article was adapted from Dr. Lewis’ poster presentation at the 2015 meeting of the American Academy of Ophthalmology. Dr. Lewis is a consultant to Alcon Laboratories, Aerie, Allergan, Aquesys, AVS, Carl Zeiss Meditec, Envisia, Glaukos, Ivantis, Oculeve, PolyActivia, and ViSci. The study was sponsored by Allergan plc, Dublin, Ireland.