Laird Harrison

April 24, 2015

SAN DIEGO — Despite contradictory results from two phase 3 trials, the use of a sustained-release dexamethasone plug to treat inflammation related to cataract surgery is effective, researchers report.

"The product works," said Shamik Bafna, MD, from the Cleveland Eye Clinic. "I think definitely it's going to be another product we can use in the armamentarium for reducing inflammation," he told Medscape Medical News.

Dr Bafna presented results from a phase 3 trial of the sustained-release dexamethasone 0.4 mg plug (OTX-DP, Ocular Therapeutix) here at the American Society of Cataract and Refractive Surgery 2015 Symposium.

The drug-eluting hydrogel punctum plug is inserted in the vertical canaliculus at the conclusion of cataract surgery. The plug fluoresces under blue light and yellow filter so clinicians can monitor its retention. Eventually it is absorbed and exits through the nasolacrimal system, so no procedure is needed to remove it.

"You don't need to worry about whether the patients are going to be compliant and take their drops," said Dr Bafna. "And patients love it because they don't need to worry about putting the drops in their eyes."

In their phase 3a study, Dr Bafna and his colleagues found an absence of anterior chamber cells and an absence of pain — two of the study end points.

However, in a previous phase 3b study, the absence of anterior chamber cells fell short of statistical significance. When this finding was announced by Ocular Therapeutix on April 6, its stock plunged.

This inconsistency might have resulted from a statistical anomaly in the phase 3b study, not from a failure of the product, Dr Bafna explained.

The 247 patients in phase 3a study were randomized, in a 2:1 ratio, to either a dexamethasone-eluting plug or a placebo plug with no active ingredient.

The proportion of patients who felt no pain was significantly higher in the dexamethasone group than in the placebo group in both the phase 3a and phase 3b studies.

The pattern was different for the absence of cells in the anterior chamber. In phase 3a, more patients in the dexamethasone group than in the placebo group had an absence of cells; however, in phase 3b, there was no significant difference.

Table. Study Outcomes

Outcome Dexamethasone Group, % Placebo Group, % P Value
Phase 3a      
   Absence of pain on day 8 80.4 43.4 <.0001
   Absence of cells on day 14 33.1 14.5 <.0018
Phase 3b      
   Absence of pain on day 8 77.5 58.8 .0025
   Absence of cells on day 14 39.4 31.3 .2182

 

In the phase 3a study, the rate of adverse events was similar in the dexamethasone and placebo groups (41.4% vs 46.4%), as was the rate of serious adverse events (1.2% vs 3.6%). None of the serious adverse events was considered to be related to the treatment.

The most common adverse events were anterior chamber inflammation and increased intraocular pressure, Dr Bafna reported.

"We didn't have as many people enrolled in the placebo arm, and a small number can make a difference," he pointed out. "If only a couple of patients had gone the other way, it would have reached statistical significance."

Another factor might have been the use of oral anti-inflammatory drugs by patients in the placebo group of the phase 3b trial, he explained.

It's too early to know whether the dexamethasone is really effective, said R. Bruce Wallace III, MD, from Louisiana State University and Tulane University in New Orleans.

"It's early on," he told Medscape Medical News. "It's novel, so it's something we need to watch."

Dr Bafna said he thinks the drug will receive approval from the US Food and Drug Administration and provide a useful alternative to anti-inflammatory eye drops.

This study was funded by Ocular Therapeutix. Dr Bafna reports financial relationships with Ocular Therapeutix, Abbott Medical Optics, Alcon, Calhoun Vision, and CXL Ophthalmics. Dr Wallace reports relationships with Bausch + Lomb and LensAR.

American Society of Cataract and Refractive Surgery (ASCRS) 2015 Symposium. Presented April 22, 2015.

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