New Regimens Can Ease the Burden of Postop Drops

The intracanalicular product is seeking US regulatory approval.

By Shamik Bafna, MD

A new dropless ocular steroid therapy option may be on the horizon. Dextenza (sustained release dexamethasone intracanalicular depot, Ocular Therapeutix), if approved, will have an initial indication for pain occurring after ocular surgery, with other indications potentially to come. This noninvasive drug delivery modality uses a proprietary hydrogel technology to provide a highly effective, self-tapered, preservative-free dose of steroid to the eye. The intracanalicular depot could become a valuable tool to help ensure patient compliance with postoperative drug administration regimens.

Figure. The dexamethasone plug being inserted (A) and in place in the canaliculus (B).

Inserted through the punctum, the hydrogel depot resides within the canaliculus and delivers a potent dosage of corticosteroid (400 µg dexamethasone) over a 4-week tapered release period (Figure). An integrated visualization aid allows physicians to verify retention of the depot during the postoperative period. Upon complete dispensation of the drug, the hydrogel depot is resorbed and exits the nasolacrimal system on its own, with no need for removal.

CLINICAL TRIALS

The intracanalicular dexamethasone depot is the first anterior segment sustained-release steroid product to enter phase 3 clinical trials, according to the manufacturer. As noted, the drug is under review and pending US Food and Drug Administration approval for the indication of pain management after surgery. It is also undergoing phase 3 clinical trials for the treatment of allergic conjunctivitis and a phase 2 clinical trial for inflammatory dry eye disease.

A phase 2 study evaluated the safety and efficacy of the dexamethasone depot after cataract extraction with IOL implantation.1 The depot group exhibited superiority over placebo for absence of anterior chamber cells at days 14 and 30 (P < .005) and was superior to placebo for absence of pain at all time points (P < .005). The drug delivery system remains in place reliably; 100% of patients in the depot group demonstrated retention through day 14 and 97% through day 30. An IOP of ≥30 mm Hg or an increase of ≥10 mm Hg from baseline was to be recorded as an adverse event. A significant increase in IOP in the study was reported in one subject in each treatment group. Both subjects experienced the event 1 day postoperatively, and both cases the event was suspected as being related to the cataract surgery. Importantly, there was no report of a treatment-related IOP increase in the study eye of any subject in the treatment group.

Significantly more patients in the placebo group were prescribed rescue medication (72.4%) compared with those receiving the depot (20.7%) at days 14 and 30. Additionally, 43.3% of patients in the placebo group experienced adverse events in the study eye, compared with 13.8% in the depot group. The placebo group also experienced more corneal edema, photophobia, and bulbar conjunctival injection.

IMPLEMENTATION

Most ophthalmologists prescribe a complex long-term postoperative steroid treatment protocol, including the important need for patients to taper the administration to prevent rebound inflammation. An intracanalicular depot offers patients the ease of a physician-administered solution, and it offers peace of mind to the surgeon because compliance is not in question. Patients must continue to use their antibiotic drop and, at the discretion of the provider, a nonsteroidal antiinflammatory drug as prescribed.

In my experience, patients do not exhibit pain upon insertion of the depot and are generally unaware of its presence. Insertion during the surgical procedure is quick, taking approximately 10 seconds. Dislodging of the plug is not a significant concern, as evidenced by the excellent retention rates noted above. In my opinion, 2 weeks of steroid medication is sufficient for the vast majority of patients; therefore an extra visit to check on retention of the plug should not be necessary.

SOLVING NONCOMPLIANCE

Patients’ noncompliance with topical drop regimens is the bane of ocular surgeons. One study of patients’ eyedrop administration after cataract surgery found that 92.5% of patients showed poor instillation technique (failing to wash hands, contaminating bottle tips, missing the eye, or using an incorrect number of drops).2 There is an obvious need for improved methods of delivery for ocular therapy. The intracanalicular dexamethasone depot offers one solution. This sustained delivery steroid ensures that patients receive the correct dosage over an adequate period of time to minimize postoperative pain and inflammation.

Other drug companies are also responding to the need for improved ocular therapy delivery methods. A compounded formulation of triamcinolone and moxifloxacin (Tri-Moxi, Imprimus Pharmaceuticals) is available. I have used this compound on my patients, and it works well. Although this compounded formulation offers the benefit of combining the steroid with an antibiotic, the intracanalicular depot offers other advantages.

Unlike the compounded drug, the dexamethasone intracanalicular depot is not a generic formulation. Both the medication and the delivery system have undergone the rigor of FDA clinical trials; this may prove to be a significant factor in terms of insurance reimbursement.

Another difference is that the intracanalicular depot is a noninvasive insertion and delivery method, whereas the compounded formulation requires injection directly into the vitreous body via the zonules or the pars plana. The injection could potentially disrupt the zonules or could cause conjunctival hemorrhage if injected in the pars plana. Although each product carries potential risks associated with delivery, I believe the noninvasive punctal insertion method presents the least risk, and it is a procedure that ophthalmologists will be comfortable performing. The depot contains a fluorescent yellow coloring, visible under a blue light, that will allow the physician to ascertain that it is still present. Once it is inserted, no further intervention by the ophthalmologist is required.

APPROVAL, REIMBURSEMENT, AND INSURANCE

Ocular Therapeutix disclosed that it received a Complete Response Letter from the USFDA for Dextenza that identified issues pertaining to deficiencies in the manufacturing process identified during a pre-new drug application approval inspection. The FDA’s letter did not identify any efficacy or safety concerns with respect to the clinical data provided in the NDA nor any need for additional clinical trials for the approval of the NDA. Ocular Therapeutix is working to resolve the manufacturing issues and gain approval for Dextenza as quickly as possible..

Ocular Therapeutix is exploring long-term reimbursement pathways to bring the dexamethasone intracanalicular depot under the umbrella of Medicare and insurance coverage to avoid placing a burden on hospitals or ambulatory surgery centers. Once FDA approval is granted, the depot will be qualified to petition for pass-through status from the Centers for Medicare and Medicaid Services (CMS). Pass-through is a transitional status granted to innovative new drugs and devices for up to 3 years. With this status, Medicare would pay for the product separately in addition to bundled facility fees. During the transitional period, CMS would track use of the product in order to make appropriate adjustments to the associated facility fees upon the expiration of pass-through status. The product would then either be included in the bundled payment or granted permanent reimbursement through a J code. Pass-through status allows surgeons the opportunity to use and assess the product for their needs without absorbing additional costs. Pass-through coverage applies only to patients with Medicare as their primary carrier; patients with traditional insurance may need to petition their carrier for coverage. Many private commercial insurance companies, however, recognize pass-through status granted by CMS.

The sustained-release dexamethasone intracanalicular depot will potentially benefit both patients and surgeons by delivering corticosteroid ocular therapy in a safe, effective, and appropriate dosage. Once approved, the depot will resolve the problem of patient noncompliance with postoperative steroid regimens. Patients will be spared the frustration and difficulty of adhering to a complex long-term, tapered drop regimen, and physicians will be assured that their patients are receiving the proper dosage of a high-quality, preservative-free, FDA-approved medication. n

1. Walters T, Endl M, Elmer TR, et al. Sustained-release dexamethasone for the treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg 2015;41:2049-2059.

2. An JA, Kasner O, Samek DA, Lévesque V. Evaluation of eyedrop administration by inexperienced patients after cataract surgery. J Cataract Refract Surg. 2014;40(11):1857-1861.

Shamik Bafna, MD
• Cleveland Eye Clinic, Brecksville, Ohio
• (216) 287-2060; drbafna@clevelandeyeclinic
• Financial disclosure: investigator for Ocular Therapeutix