iDose: An Intraocular Drug-Eluting Delivery Device for Glaucoma

Glaucoma providers are enjoying a renaissance of innovation in treatment options. One evolving category is sustained-release drug delivery devices that deploy pharmacologic molecules while taking the responsibility for their instillation out of our patients’ hands. In a 2015 study of more than 1,200 newly diagnosed glaucoma patients who were started on topical therapy, only 20% had persistently good treatment adherence at 1 year and only 15% at 4 years.¹

Sustained-release glaucoma medication options are expanding, but currently there is only one FDA-approved option: the bimatoprost implant (Durysta, Allergan). Other glaucoma drug delivery devices in phase 2 or 3 FDA trials can be subdivided into nonsurgical external modalities and surgically implanted devices. The external modalities include latanoprost microdose delivery with Optejet (Microprost, Eyenovia), latanoprost delivery via an intracameral implant (OTX-TIC, Ocular Therapeutix), and latanoprost or travoprost delivery via a punctal plug (L-evolute and T-evolute, Mati Therapeutics). Surgically implanted devices in trials include two travoprost delivery vehicles, ENV515 (Envisia Therapeutics) and iDose (Glaukos).^2-4

SURGICAL IMPLANT

I’ve been intimately involved with iDose as a subinvestigator in both phase 2 and 3 clinical trials. iDose is a 1.8 x 0.5 mm biocompatible titanium implant that releases a proprietary formulation of travoprost inside the anterior chamber.⁵ Eluting travoprost inside the eye bypasses the barrier of corneal permeability, allowing the device to release micro-amounts of the active drug molecule over time.⁵ The implant comprises three parts: a scleral anchor that affixes into the trabecular meshwork (TM), the body of the device that serves as the drug reservoir, and the elution membrane that titrates travoprost release (Figure 1).

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Figure 1. An illustration showing the implantation site for the iDose (A). The device implanted in an eye (B).

In our practice, implantation is performed as a standalone procedure in an ASC. After creating a 2.4-mm incision, the surgeon uses an ab interno approach to visualize the anterior chamber angle. The scleral anchor is implanted into the TM, and the surgeon ensures secure attachment by nudging the device (see Watch It Now).

The iDose is nudged to ensure secure attachment.

CLINICAL TRIALS

As previously mentioned, a phase 3 trial of iDose is under way.⁶ Patients in the study are randomly assigned to receive a fast-elution implant with 78 µm of travoprost, a slow-elution implant with 78 µm of travoprost, or sham surgery followed by twice-daily topical timolol maleate 0.5%.⁶ The primary endpoint of IOP at 3 months and secondary endpoint of IOP at 12 months are yet to be determined pending study completion, but to date these endpoints mirror closely the published endpoints from the phase 2 trial.⁶

The phase 2 study included 154 patients who were randomly assigned 1:1:1 to the fast-eluting implant, slow-eluting implant, or the control treatment of sham surgery followed by twice-daily topical timolol maleate 0.5%. All three cohorts had unmedicated baseline IOPs near 25 mm Hg. The primary endpoint was IOP reduction at 12 weeks postimplantation, with secondary endpoints including IOP at 12 months, avoidance of additional topical medications at 12 weeks, and safety outcomes.⁵

At the primary 12-week endpoint, the fast-eluting implant lowered IOP by 8.5 mm Hg (a 33% decrease from baseline), the slow-eluting implant lowered IOP by 8 mm Hg (a 32% decrease), and timolol lowered IOP by 7.6 mm Hg (a 30% decrease).⁵ This IOP reduction was stable and sustained to 12 months postimplantation (Figure 2).⁵ The need for additional glaucoma drops through 12 weeks was avoided by 82% of patients in both study groups and 74% in the control group.⁵

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Figure 2. Phase 2 trial results at 12 weeks (A) and 1 year (B) postoperative.

Safety outcomes were favorable. There were no serious adverse events, and the mild to moderate adverse events resolved without sequelae. Through 12 weeks, there was no increased conjunctival hyperemia in either treatment arm, and travoprost was not detected in any study patient’s blood serum.⁵

QUESTIONS REMAIN

Even as iDose makes positive advances in completing its phase 3 clinical trial, there are still questions to be answered.

No. 1: What are patients’ preferences regarding the mode of glaucoma treatment? In multiple studies, patient preference tilts toward drops, due to the efficacy of modern topical drop molecules coupled with their traditional status as the primary treatment option. In studies reviewing patients’ preferences in drug delivery options, extraocular approaches and devices were favored over intraocular implants.^7,8 At best, 60% of patients surveyed regarding their choices for drug delivery expressed preference for an intraocular implant.⁹ One study showed a low of 30% preference. Higher glaucoma severity has been associated with higher drug delivery adoption across all device platforms.⁹

No. 2: How do eye care providers manage patients with implanted devices after the repository is empty? Possibilities include leaving the biocompatible implant in place, refilling the implant, or removing and, if needed, replacing the implant.

No. 3: What is the cost of these devices, and what is the potential reimbursement pathway? These devices are still in clinical trials, and the pathway has not been finalized. However, reimbursement will be imperative to determine true patient treatment preferences.

CONCLUSION

The paramount goals for all glaucoma drug delivery devices include improving patient compliance, increasing patient convenience, and decreasing medication side effects. The iDose travoprost implant has the potential, if approved, to check all these boxes.