Bimatoprost SR

Nonadherence to treatment regimens is endemic in glaucoma. Up to 80% of patients with glaucoma may not use topical medication as prescribed.¹ Poor adherence is associated with worsening vision and higher overall health care costs.² Because barriers to adherence include patient forgetfulness, difficulty administering eye drops, and the burden of dosing frequency,¹ there is an unmet need for glaucoma therapy that does not require daily eye drop instillation.

A biodegradable bimatoprost sustained-release implant (Bimatoprost SR, Allergan), currently in development for the treatment of open-angle glaucoma and ocular hypertension, could be one way to address the problem of nonadherence in glaucoma by providing long-term IOP lowering without the need for eye drops.³ The solid, rod-shaped implant consists of the prostaglandin analogue (PGA) bimatoprost within the company’s Novadur platform for drug delivery.

After a prefilled, single-use applicator is used to place the implant intracamerally in the eye (Figure), the implant slowly releases the drug as the copolymer matrix biodegrades. The implant was designed to lower IOP for at least 4 months.

Figure. Bimatoprost SR single-use applicator (top). Implant positioned next to a dime for size comparison (bottom).

STUDY RESULTS

The first clinical trial of the implant in humans was a dose-ranging, phase 1/2 study that enrolled 75 patients with open-angle glaucoma. Each dosing strength that was tested effectively lowered IOP in a dose-dependent manner over the first 16 weeks of the study, with efficacy similar to that of a topical PGA.³ An extended duration of effect was seen in some patients; a single administration of Bimatoprost SR controlled IOP for up to 2 years without rescue or retreatment in 28% of patients.⁴ The product’s safety profile was favorable, and some adverse events associated with use of topical PGAs, such as eyelash growth and iris pigmentation, did not occur in eyes that received an implant.

Two 20-month, phase 3 randomized studies have enrolled 1,122 patients with glaucoma or ocular hypertension and are ongoing. Both studies compare two dosage strengths of Bimatoprost SR, administered at day 1, week 16, and week 32, to twice-daily topical timolol. Topline 3-month results have been reported, and most patients have tolerated the study treatment.^5,6 In both studies, Bimatoprost SR has reduced IOP by about 30% over 12 weeks and met the primary endpoint of noninferiority to timolol in IOP lowering through week 12. Initial long-term data from these studies suggest that a majority of patients will require no other IOP-lowering treatment for 1 year after receiving the last implant. Additional safety and efficacy data will be reported at study completion.

1. Olthoff CM, Schouten JS, Van de Bourne BW, et al. Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension an evidence-based review. Ophthalmology. 2005;112:953-961.

2. Iuga AO, McGuire MJ. Adherence and health care costs. Risk Manag Healthc Policy. 2014;7:35-44.

3. Lewis RA, Christie WC, Day DG, et al. Bimatoprost sustained-release implants for glaucoma therapy: 6-month results from a phase I/II clinical trial. Am J Ophthalmol. 2017;175:137-147.

4. Craven R, Walters T, Christie WC, et al. 24-month phase 1/2 clinical trial of bimatoprost sustained-release implant (bimatoprost SR) in glaucoma patients. Paper presented at: American Academy of Ophthalmology Annual Meeting; November 11-14, 2017; New Orleans.

5. Allergan announces positive topline phase 3 clinical data for Bimatoprost SR (sustained-release) implant for IOP lowering in patients with open-angle glaucoma or ocular hypertension. https://www.allergan.com/news/news/thomson-reuters/allergan-announces-positive-topline-phase-3-clinic.aspx. Accessed May 16, 2019.

6. Allergan announces positive 3-month topline results from second phase 3 study of Bimatoprost SR (sustained-release) implant for lowering intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. https://www.allergan.com/news/news/thomson-reuters/allergan-announces-positive-3-month-topline-result. Accessed May 16, 2019.