Sustained-release dexamethasone products demonstrate positive results in pivotal trials

May 8, 2017

Dexamethasone insert 0.4 mg (Dextenza Ocular Therapeutix) met its primary endpoints in a third pivotal trial investigating its efficacy and safety for the treatment of inflammation and pain after cataract surgery, said Eric D. Donnenfeld, MD.

Dexamethasone insert 0.4 mg (Dextenza Ocular Therapeutix) met its primary endpoints in a third pivotal trial investigating its efficacy and safety for the treatment of inflammation and pain after cataract surgery, said Eric D. Donnenfeld, MD.

Presenting data from the prospective, multicenter, randomized, double-masked phase III study, Dr. Donnenfeld said he was excited about the results because he anticipates they will support FDA approval of the intracanalicular insert in the near future.

“Corticosteroids are a mainstay of cataract surgery medication regimens, but topical regimens are complex, depend on patient compliance, and have the potential to cause ocular surface toxicity at a time when the eye is particularly vulnerable,” said Dr. Donnenfeld, clinical professor of ophthalmology, NYU Langone Medical Center, New York. “The development of alternatives to topical treatment is what it is all about.”

Dr. Donnenfeld also presented positive results from a phase III study investigating another investigational one-time corticosteroid medication, IBI-10090 (Dexycu, Icon Bioscience). IBI-10090 is a novel, bioabsorbable drug-delivery product for anterior chamber intracameral placement of dexamethasone. It is given as a single 5 µL injection after the completion of cataract surgery.

The study Dr. Donnenfeld presented showed IBI-100090 demonstrated similar efficacy and safety compared with “standard of care”-topical prednisolone acetate 1.0% four times daily as standard of care.

 

Dexamethasone intracanalicular insert results

The third phase III study of the dexamethasone intracanalicular insert was conducted after the first two phase III studies generated mixed results for the inflammation primary endpoint.  

The third trial randomly assigned 438 patients undergoing clear corneal cataract surgery 1:1 to receive the dexamethasone insert or a placebo drug delivery vehicle. Patients were followed for 45 days at visits scheduled on days 2, 4, 8, 14, 30, and 45 after surgery.

Primary endpoints were absence of pain in the study eye at day 8 and absence of anterior chamber cells at day 14. The difference between study groups for both endpoints was highly statistically significant (p < 0.0001) favoring the dexamethasone insert, Dr. Donnenfeld reported.

At day 8, 79.6% of patients in the dexamethasone insert group compared with 61.3% of control patients achieved absence of ocular pain. Absence of anterior cell inflammation at day 14 was achieved in 52.3% of dexamethasone insert eyes and 31.2% of eyes in the control group.

Analyses of secondary endpoints also showed treatment benefits. At all study visits through day 30, a significantly higher proportion of patients in the dexamethasone insert group compared with controls were free of ocular pain. Beginning at day 4 and at all subsequent follow-up visits, a significantly higher proportion of patients in the dexamethasone insert group compared with controls had absence of anterior chamber cells.

Presenting the primary efficacy results from all three trials, Dr. Donnenfeld noted there was consistent benefit for the dexamethasone insert to significantly increase the proportion of patients who were free of ocular pain at day 8 compared with control. About 80% of patients receiving the dexamethasone insert achieved that stringent endpoint.

“Pain after cataract surgery is not to be looked at lightly because it is how patients judge the effectiveness of the operation,” Dr. Donnenfeld said.

 

Safety review

The safety review showed no serious treatment-related adverse events, and the insert was well-tolerated as no patients withdrew from the study because of an adverse event. The only ocular adverse events observed in >5% of eyes were eye inflammation and increased IOP. The incidence of eye inflammation was 8.3% in the dexamethasone insert group and 20.4% in the control eyes. Increased IOP rates were 7.4% in the dexamethasone insert group and 2.7% in the controls.

“Both novel dexamethasone products seem to be in the sweet spot for controlling inflammation and minimizing problems with IOP spikes,” Dr. Donnenfeld said. “Overwhelming inflammation with a corticosteroid may be very effective, but the trade-off is that it will cause more IOP spikes. The flip side for having a little lower efficacy is a lot more safety.”

Dr. Donnenfeld is a consultant to Icon Bioscience.