Results of two phase III trials with dexamethasone intracanalicular depot are highlighted. Both trials met the endpoints for postsurgical pain, but only one trial met the endpoints for postoperative inflammation
Reviewed by Joseph Gira, MD
St. Louis, MO-A novel sustained drug depot that aims to treat ocular pain and inflammation after cataract surgery-while also allaying concerns associated with adherence-has moved one step closer toward approval.
Ocular Therapeutix submitted its dexamethasone intracanalicular depot (Dextenza) for FDA approval for postsurgical ocular pain following two successful phase III trials, said lead author Joseph Gira, MD, who presented the results of two phase III trials.
“After cataract surgery, using dexamethasone drops is extremely important,” said Dr. Gira, Ophthalmology Consultants, St. Louis, MO.
Drops can help prevent inflammation, prevent macular edema, and ensure good outcomes in regard to vision, he noted.
“But we have to rely on patients to administer drops and a lot of patients are not very compliant with their medications,” Dr. Gira added. “The depot plug takes it out of the patient’s hands. You insert the plug with the drug already loaded at the conclusion of surgery, and that’s it.”
Both trials met the endpoints for postsurgical pain, but only one trial met the endpoints for postoperative inflammation.
Both studies used a polyethylene glycol-based hydrogel drug depot inserted into the lower vertical canaliculus following cataract surgery. Patients either received a plug containing 0.4 mg of dexamethasone or a placebo plug. The drug-loaded plug is intended to replace the steroid eye drops typically prescribed following cataract surgery.
The plugs provide sustained and tapered drug delivery to the ocular surface for up to 30 days. Once inserted, the plugs are invisible under normal light but fluoresce yellow under blue light for easier placement and to confirm retention.
The plugs are eventually resorbed and flushed via the nasolacrimal system and do not need to be removed. The plugs can be engineered for longer or shorter persistence in the canaliculus and drug release depending on the clinical application.
“These plugs are very easy to insert,” Dr. Gira said. “If the surgeon has placed punctal plugs before, and almost all of us have, it is the same technique you have used before. Not only does this drug depot take dexamethasone administration out of the patient’s hands, it’s far more convenient for the patient. They loved not having to worry about eye drops.
“And as the surgeon, you don’t have to worry about them missing a dose or not using their drops at all,” he said. “Using an implantable drug depot is a win for everyone.”
The two studies were each conducted at 16 unique sites across the United States. The first study had 247 patients randomly assigned to drug depot or placebo in a 2:1 ration. The second study had 240 patients randomly assigned. All patients had postoperative evaluations at days 2, 4, 8, 14, 30, and 60 following cataract surgery.
Primary endpoints were the absence of anterior chamber (AC) cells, a score of zero, at day 14 and the absence of pain, also a score of zero, at day 8.
The first study met the primary endpoints for both pain (p < 0.0001) and inflammation (p = 0.0018), Dr. Gira noted. It also showed a strong safety profile.
The second study met the pain endpoint (p = 0.0025) but failed to meet the inflammation endpoint (p = 0.2182). The second study also showed a strong safety profile.
A pooled ad hoc analysis of the combined study populations met the inflammation endpoint (p = 0.0025). Both trials met two secondary inflammation endpoints, differences in mean AC cell score at days 8 and day 14 and absence of AC flare at days 8 and 14. The trial sponsor (Ocular Therapeutix) decided to pursue only the postoperative pain indication in its first FDA submission of the product.
A third phase III study for inflammation is planned, Dr. Gira said.
“There were not huge differences in anterior chamber cells, and you can expect to see differences between surgeons, between different surgical platforms, and different techniques,” he said. “There will be more detailed analyses to identify the differences before they go back for another phase III trial.”
The good news, he added, is that both trials showed very strong safety results.
There were no product- or treatment-related serious adverse events in either study. There was one case of conjunctivitis in the placebo arm of the first study and one case of dacryocanaliculitis in the placebo arms of the second study. The first study had one patient with eyelid irritation and one with increased lacrimation, while the second study had one patient with an IOP increase of 10 mm Hg or more over baseline.
“We saw a very strong safety profile in both studies,” Dr. Gira said. “The surgeons all loved the system and so did the patients. Not having to worry about drug delivery, not having to worry about removing the plug, and not having any significant adverse events are huge advantages that you just don’t get with eye drops.”
Joseph Gira, MD
This article was adapted from Dr. Gira’s presentation at the 2016 meeting of the American Society of Cataract and Refractive Surgery. Dr. Gira has no financial relationship with Ocular Therapeutix. Sustained-release intracanalicular depots are investigational new drugs and not commercially available in the United States.