Durysta (Bimatoprost Implant)
Indications
The bimatoprost implant (Durysta, Allergan, Irvine CA, USA) was approved by the Food and Drug Administration (FDA) on March 5th, 2020 for reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHTN). The implant is the first sustained release therapy to be approved for this purpose.
Pharmacology
The bimatoprost implant is composed of biodegradable polymers designed to release bimatoprost in a non-pulsatile, steady-state manner over a 90-day period. In an animal study involving treatment of dogs with the bimatoprost implant (15ug), 80.5% of the bimatoprost load was found to be released by day 51 and 99.8% had been released by day 80. Compared to topical dosing, concentrations of active drug were 4,400-fold higher at the iris-ciliary body with the bimatoprost implant[1].
Mechanism of Action
Bimatoprost belongs to the prostaglandin analog (PGA) drug class and has been shown to lower IOP by increasing aqueous humor outflow via both the conventional trabecular route as well as the uveoscleral route[2]. Results from a study of normotensive beagle dogs that received the bimatoprost implant (30ug) suggest that the agent may also increase aqueous humor outflow by decreasing episcleral venous pressure[3].
Administration
The bimatoprost implant is preloaded within a sterile applicator with a 28-gauge needle tip. Under aseptic conditions, the practitioner inserts the needle into clear cornea, enters the anterior chamber, and then depresses an actuator button to release the implant. Following release of the implant, the needle is removed and the patient is instructed to sit upright for at least one hour.
The implant then will rest in the inferior anterior chamber angle [FIGURE].
Efficacy
The efficacy of the bimatoprost implant was investigated in two 20-month phase III trials involving 1,122 subjects that were randomized to treatment with the implant versus topical timolol eye drops[4]. Patients that were randomized to the bimatoprost implant had the drug administered in the study eye on day 1, week 16, and week 32. Patients randomized to topical timolol were treated with twice daily dosing. By week 12, patients randomized to the bimatoprost implant achieved an IOP reduction from 24.6 to 17.7 mmHg, representing approximately 30% reduction from baseline. The bimatoprost implant met pre-defined criteria for non-inferiority compared to timolol.
In a separate phase I/II, dose ranging study, 63 participants were randomized to 6, 10, 15, or 20ug bimatoprost implant administration in their study eye and topical bimatoprost once daily in their fellow (control) eye and followed for 24 months[5]. Eyes were permitted to receive a single repeat implant administration or rescue topical IOP-lowering medication during the study period. By 24 months, IOP was reduced from baseline by 7.5, 7.3, 7.3, and 8.9 mmHg in the 6, 10, 15, and 20ug bimatoprost implant groups, respectively. A single administration of the bimatoprost implant was found to control IOP in 40% of patients for up to 12 months and in 28% of patients for up to 24 months. In eyes treated with topical bimatoprost, mean IOP reduction from baseline was 8.2mmHg at 24 months.
Safety
The bimatoprost implant is contraindicated in individuals with active or suspected ocular or periocular infections, corneal endothelial cell dystrophy, prior corneal transplantation, absent or ruptured posterior lens capsule and in individuals with a history of hypersensitivity to bimatoprost[6].
In the phase III studies evaluating the implant, the most common ocular adverse reaction was conjunctival hyperemia in 27% of patients. Other adverse reactions reported in 5-10% of patients included foreign body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eye irritation, increased intraocular pressure, corneal endothelial cell loss, blurred vision, iritis, and headache[4].
Patient Experience
In a phase I/II evaluation of the bimatoprost implant, 67-100% of patients across dose-ranging groups reported that the procedure was somewhat or much less burdensome than expected. Across all dose strengths, 82.9% of patients reported that they were extremely likely or very likely to undergo another administration of the implant and 88.6% reported that they would recommend the procedure to someone else[5].
Summary
Lowering of IOP is the only proven method to decrease risk of development and/or worsening glaucomatous optic neuropathy. Topical medical therapy is an effective strategy, but several barriers exist to long-term treatment. The bimatoprost implant has been shown to be efficacious and relatively safe. The implant addresses an area of need in glaucoma management.
References
- ↑ Seal JR, Robinson MR, Burke J, et al. Intracameral sustained-release bimatoprost implant delivers bimatoprost to target tissues with reduced drug exposure to off-target tissues. J Ocul Pharmacol Ther. 2019;35(1):50-57.
- ↑ Curran MP. Bimatoprost. A review of its use in open-angle glaucoma and ocular hypertension. Drugs Aging 2009;26(12):1049-1071.
- ↑ Lee SS, Burke J, Shen J, et al. Bimatoprost sustained-release intracameral implant reduces episcleral venous pressure in dogs. Veterinary Ophthalmology. 2018;21(4):376-381.
- ↑ 4.0 4.1 Safety and efficacy of bimatoprost sustained-release in patients with open-angle glaucoma or ocular hypertension. ClinicalTrials.gov Identifier NCT02250651.
- ↑ 5.0 5.1 Craven ER, Walters T, Christie WC, et al. 24-month phase I/II clinical trial of bimatoprost sustained-release implant (bimatoprost SR) in glaucoma patients. Drugs. 2020;80:167-179.
- ↑ DurystaTM [package insert]. Irvine, CA: Allergan USA, Inc.
