Intracanalicular drug depot may fill unmet need for better topical therapy

Take-home message: A sustained-release dexamethasone intracanalicular depot may be able to treat post-cataract surgery inflammation without causing spikes in IOP. The product’s one-time administration may also improve compliance and convenience.

By John Berdahl, MD, Special to Ophthalmology Times

Sioux Falls, SD-With all the improvements in cataract surgery over the years, the need for better topical therapies post-procedure continues to be unmet.

Post-surgical anti-inflammatories-such as corticosteroids-are a vital element in the process to promote healing and combat pain and inflammation, which can lead to other issues. However, while necessary to obtain positive outcomes, the inconsistency of patient delivered steroids drops could lead to variable response.

Additionally, the post-surgical drop regimen can be inconvenient, costly, and confusing for patients. Many struggle with adherence, especially those previously inexperienced with drop administration.¹

These issues are exacerbated when long-term administration is necessary. According to IMS Health Data, more than 20 million anti-inflammatory eye drop prescriptions were filled in 2015-corticosteroids comprising about 8.9 million of those.² Studies of patients with chronic diseases have found that only 10% of patients showed a consistently proficient pattern of compliance through 1 year³ and only 15% adhered consistently over 4 years.⁴

Though these studies highlight long-term medications, they serve to show the difficulty patients often have with self-administering ocular medications. Treatment options that reduce the number of drops a patient must administer and put control over adherence in the physician’s hands are of great benefit to the patient. With the physician at the helm, medication delivery is assured-helping improve positive outcomes.

New mechanism of action

The question then becomes: What is the best way to deliver necessary steroid medications? Dropless cataract surgery (Imprimis Pharmaceuticals) may be a viable approach.

However, some physicians believe a postoperative nonsteroid anti-inflammatory drug is still necessary to combat inflammation. Additionally, not all patients are good candidates for the dropless approach due to preference or pathology. Those who will need a steroid post surgery will continue to struggle through the confusing drop regimen and often expensive topical therapy treatments.

With the advent of an ocular pain treatment (Dextenza, Ocular Therapeutix), ophthalmologists worldwide may have a new alternative to traditional steroid therapy with drops. The preservative-free, hydrogel-based, intracanalicular depot delivers a sustained-release dose of dexamethasone over a period of 4 weeks.

The intracanalicular depot form-fits within the canaliculus. The depot becomes soft following insertion through contact with moisture, thereby contracting in length and expanding in diameter once in place. As it is administered by the physician in a one-time procedure, adherence is assured and convenience for the patient is greatly improved.

Retention rates in the phase II trials were strong, with the intracanalicular drug depot group demonstrating 100% retention through day 14, and 97% through day 30.⁵ Current phase III trials are demonstrating similarly strong rates.

Placement of the intracanalicular depot is a simple procedure that is familiar to ophthalmologists and well tolerated by patients.

However, the depot will swell after contact with moisture so surgeons must be deliberate when inserting it. The depot also contains a visualization aid for retention monitoring, making the depot visible under blue light and under blue light with a yellow filter, though it will not be visible under normal light. Once drug delivery is complete, the depot is essentially hydrolyzed and exits the patient’s nasolacrimal system without the need for physician intervention or removal.

Dexamethasone is one of the most potent corticosteroids available. Widely used in ophthalmology decades ago, it fell out of favor due to a reputation for IOP spikes. However, in small, controlled aliquots IOP spikes may not be a concern as in decades past.

An intracanalicular drug depot essentially provides an improved delivery system for a familiar drug while addressing the former drawbacks. The potency of the drug allows for the small size of the delivery system, as less of the drug is needed for the desired effect.

While an argument may be made that a less potent steroid would be a better alternative as it may involve lesser risk of IOP spikes, a less potent steroid would not solve the problem of delivery as a greater quantity would be required. With intracanalicular drug depots, it is possible to provide significant positive results with a small volume.

Safety and efficacy

The intracanalicular depot is currently in phase III trials for the treatment of postoperative inflammation and pain and is illustrating promising safety and efficacy. While this data continues to be analyzed, the drug appears to be well tolerated with a good safety profile as evidenced by the fact that in the clinical trials, despite using a very potent steroid, a comparatively low rate of IOP spikes (≥10 mm Hg) were demonstrated posterative day 14 (1/322 or 0.3%).

In the phase II data,⁵ the intracanalicular depot group demonstrated statistically significant superiority over placebo for the absence of pain and cells in the anterior chamber, evidence that the delivery system of this well known drug is helping mitigate the known unwanted side effects of its potency.

Looking forward

It remains to be seen how intracanalicular drug depots will change treatment regimens if FDA approval is gained. Physicians strive to do what is in patients’ best interests and that includes providing the safest, most cost-effective, convenient, and efficacious options for postoperative care.

Use of intracanalicular drug depots over an approach, such as dropless cataract surgery, would necessitate the addition of an antibiotic drop post-surgery. However, one point in the intracanalicular depot’s drug favor is it will be an FDA-approved medication and delivery system. This will be of significant importance in terms of insurance reimbursement pathways.

Cataract surgery is already an impressive procedure. Being able to reduce the inconvenience and confusion of a strict topical therapy regimen post-surgery for patients while simultaneously providing optimal prevention of inflammation is an exciting development.

References

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

2. IMS Health.

3. Friedman DS, Quigley HA, Gelb L, Tan J, Margolis J, Shah SN, Kim EE, Zimmerman T, Hahn SR. Using pharmacy claims data to study adherence to glaucoma medications: methodology and findings of the glaucoma adherence and persistency study (GAPS). Invest Ophthalmol Vis Sci. 2007;48:5052-5057.

4. Newman-Casey PA, Blachley T, Lee PP, Heisler M, Farris KB, and Stein JD. Patterns of glaucoma medication adherence over four years of follow-up. Ophthal. 2015;122: 2010–2021.

5. Ocular Therapeutix. Dextenza (sustained release dexamethasone) intracanalicular depot. Retrieved from Ocular Therapeutix website Feb. 28, 2016. http://www.ocutx.com/pipeline/dexamethasone-punctum-plug.

John Berdahl, MD

E: john.berdahl@vancethompsonvision.com

Dr. Berdahl is in practice at Vance Thompson Vision, Sioux Falls, SD. He is a paid consultant for Ocular Therapeutix.