New topical steroid reduced postoperative inflammation in phase 3 trials

CHICAGO — A new ophthalmic steroid was shown to reduce inflammation, pain and photophobia over the course of a month in two phase 3 multicenter clinical trials, according to a surgeon speaking here.

Michael Korenfeld

Michael Korenfeld, MD, presented results on difluprednate ophthalmic emulsion 0.05%, a topical ophthalmic glucocorticosteroid, at the American Society of Cataract and Refractive Surgery meeting.

Difluprednate is a difluorinated derivative of prednisolone with potent antiinflammatory activity, according to Sirion Therapeutics, which is awaiting U.S. Food and Drug Administration approval of the drug. Sirion is planning to market the drug under the brand name Durezol, pending FDA approval.

"The drug is engineered to be potent through fluorination. There are two fluorides on there," Dr. Korenfeld said. "And there is a component that improves lipophilicity so that it can achieve greater concentrations in the anterior chamber."

Difluprednate was tested in 438 patients who exhibited inflammation 1 day after ocular surgery. Patients were randomized to receive 0.05% difluprednate twice a day (111 patients), 0.05% difluprednate four times a day (107 patients), placebo twice a day or placebo four times a day (220 patients total in placebo groups).

Patients received the drug or placebo for 2 weeks, followed by a tapering period for 2 weeks and then 1 week of a safety period, according to Dr. Korenfeld.

Investigators found that the twice-a-day and four-times-a-day dosing groups were superior to placebo in terms of meeting the study's primary endpoint: Achieving an anterior chamber cell grade of zero on day 8 after treatment, he said.

Specifically, 30% of patients in the twice-daily treatment group achieved grade zero vs. 9% of the placebo group, and 35% of the four-times-daily group achieved grade zero. Difluprednate also maintained superiority over placebo through the 15-day treatment period, with 56% of the twice-daily group and 63% of the four-times-daily group achieving grade zero vs. 16% of the placebo group.

Secondary endpoints compared changes at all time points between the two treatment groups in anterior chamber cell grade and count, resolution of the pain/discomfort and photophobia, as well as resolution of signs of inflammation.

In terms of complications, the mean IOP throughout the study remained "well within the normal range" in all groups, Dr. Korenfeld said. The rate of IOP was 2.7% to 2.8% in both treatment arms.

"The BID and QID groups were comparable in efficacy and safety, although a comparison of these two groups was not a part of this particular study," Dr. Korenfeld said. "There are other ongoing studies using the difluprednate molecule in other settings of inflammation."