Bimatoprost Sustained-Release Implants for Glaucoma Therapy: 6-Month Results From a Phase I/II Clinical Trial

Lewis, Richard A.; Christie, William C.; Day, Douglas G.; Craven, E. Randy; Bejanian, Marina; Lee, Susan S.; Goodkin, Margot L.; Zhang, Jingyan; Whitcup, Scott M.; Robinson, Michael R.; Aung, Tin; Beck, Allen D.; Coote, Michael; Crane, Charles J.; Crichton, Andrew; Durcan, F. Jane; Flynn, William J.; Gagné, Sébastien; Goldberg, Damien F.; Jinapriya, Delan; Johnson, C. Starck; Kurtz, Shimon; Mansberger, Steven L.; Perera, Shamira; Rotberg, Michael H.; Saltzmann, Robert M.; Schenker, Howard I.; Tepedino, Michael; Yap-Veloso, Maria Imelda R.; Uy, Harvey S.; Walters, Thomas R.

doi:10.1016/j.ajo.2016.11.020

Cited by 98 publications

(116 citation statements)

References 26 publications

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“…A more effective approach to local IOP-lowering therapy is sustained delivery of drugs. A variety of approaches to this area are being tried, including reservoirs attached to the eye, punctal plugs containing medication [18], rings worn on the eye surface that elute drug [19], and depot delivery of medication into the anterior chamber [20] or under the conjunctiva [21]. Some of these are approaching approval for general use, while others are still in animal or early human trials.…”

Section: Sustained Delivery Is An Answermentioning

confidence: 99%

21st century glaucoma care

Quigley

2018

Eye

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Glaucoma care has evolved dramatically over the past generation, with changes that have incorporated new technology and improved understanding of the disease process. A major need is to construct a useful definition of glaucomatous optic neuropathy that can be used to compare data across clinical research studies. The treatment of glaucoma should now be based on achievement of a goal target for intraocular pressure, unique to each patient. Adherence with eye drop treatment is far from ideal and can be improved using reminder systems. Sustained delivery of glaucoma medication is on the horizon. New surgical approaches to glaucoma are being actively studied but have not as yet found their place in its care, with rigorous testing against present treatments needed.

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Section: Sustained Delivery Is An Answermentioning

confidence: 99%

21st century glaucoma care

Quigley

2018

Eye

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“…A bimatoprost sustained-release intracameral implant (Bimatoprost SR) is currently in development for the treatment of open-angle glaucoma. Bimatoprost SR is a rod-shaped implant sized to fit within the intracameral space 16 and contains the PGA bimatoprost in the NOVA-DUR (Allergan plc, Dublin, Ireland) biodegradable, solid polymer drug delivery system. 17 The implant is designed to slowly release the drug over a period of 4 to 6 months.…”

Section: Introductionmentioning

confidence: 99%

Bimatoprost sustained‐release intracameral implant reduces episcleral venous pressure in dogs

Lee

Burke

Shen

et al. 2018

Veterinary Ophthalmology

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“…Because the effects of PGAs on MMP expression are concentration dependent, we reasoned that it might be possible to achieve more extensive tissue remodeling, and a longer remnant effect on IOP, if a higher drug concentration was achieved in the outflow tissues. The drug content of the 10-mg Bimatoprost SR that was developed is similar to that of a single drop of topical bimatoprost 0.03% ophthalmic solution, 100 but the implant can achieve higher bimatoprost concentrations in outflow tissues because it takes advantage of an intracameral route for drug delivery. Thus, >80% of drug is delivered to outflow tissues, whereas <5% of drug reaches intraocular tissues after topical administration of an eye drop.…”

Section: Exploiting Mmps In Glaucoma Therapy: Development Of a Bimatomentioning

confidence: 99%

“…During the first clinical trial of Bimatoprost SR, the phase 1/2 APOLLO study, 100,111 the formulation was modified to optimize the rate of biodegradation and drug release, and 6-, 10-, 15-, and 20-mg dose strengths of a second-generation implant were tested in 75 patients with open-angle glaucoma in the study eye. In APOLLO, patients received 1 or at most 2 administrations of implant and were followed for 2 years.…”

Section: Exploiting Mmps In Glaucoma Therapy: Development Of a Bimatomentioning

confidence: 99%

Matrix Metalloproteinases and Glaucoma Treatment

Weinreb

Robinson

Dibas

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from in vivo and in vitro studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect. IOP, intraocular pressure; MMP, matrix metalloproteinase; MT-MMP, membrane-type MMP; TIMP, tissue inhibitor of metalloproteinase.MMPS AND GLAUCOMA TREATMENT 209 210 WEINREB ET AL.

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Bimatoprost Sustained-Release Implants for Glaucoma Therapy: 6-Month Results From a Phase I/II Clinical Trial

Abstract: Bimatoprost SR demonstrated favorable efficacy and safety through 6 months. All dose strengths were comparable to topical bimatoprost in overall IOP reduction through week 16. A single administration controlled IOP in the majority of patients for up to 6 months.

Cited by 98 publications

References 26 publications

21st century glaucoma care

21st century glaucoma care

Bimatoprost sustained‐release intracameral implant reduces episcleral venous pressure in dogs

Matrix Metalloproteinases and Glaucoma Treatment

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