Sirion's supplemental NDA for difluprednate accepted

Tampa, FL

-The FDA has accepted for review a supplemental new drug application (NDA) submitted by Sirion Therapeutics Inc., which seeks market approval of difluprednate ophthalmic emulsion 0.05% (Durezol) for the treatment of endogenous anterior uveitis, according to a statement issued by Sirion.

“Uveitis is a debilitating and painful condition, and [it] is one of the leading causes of blindness in the United States,” said Barry Butler, chief executive officer of Sirion. “We are encouraged that the FDA is reviewing the application of our drug, which has the potential to treat this sight-threatening condition.”

Approved since June 2008 for the treatment of postoperative inflammation and pain associated with ocular surgery, difluprednate is a topical corticosteroid that does not contain benzalkonium chloride, a preservative that is known to cause corneal toxicity with prolonged use. This fact is of particular importance in patients with uveitis, who often require long-term treatment with steroids, the company said.

Approval was based on data from several clinical trials, the most recent of which included 90 patients with endogenous anterior uveitis. Researchers compared difluprednate given four times daily with prednisolone acetate ophthalmic suspension 1% (Pred Forte, Allergan), given eight times daily. Comparable results were seen with both agents in the reduction of mean anterior chamber cell grades at day 14 (a 2.1-mean reduction in cell grade with difluprednate, compared with 1.9 with prednisolone). Difluprednate was superior in almost every efficacy measure in the study, including reduction of anterior chamber flare, and in the reduction of the signs and symptoms of inflammation, according to the company.

In addition, 12.5% of patients treated with prednisolone withdrew from the trial because of lack of efficacy. No patients treated with difluprednate withdrew.

Two phase III clinical trials, conducted by Senju Pharmaceuticals Ltd. in Japan, were included in the application as well. In one study, difluprednate was significantly more effective in patients with anterior uveitis and panuveitis than treatment with betamethasone ophthalmic solution 0.1%. In the second study, difluprednate effectively reduced anterior chamber cell, flare, and total sign and symptom scores in patients with severe endogenous anterior uveitis and panuveitis.

“The studies included in this application demonstrate the efficacy of difluprednate ophthalmic emulsion 0.05% in quickly resolving uveitis, a disease state in which prompt eradication of inflammation is key in preserving vision,” said Roger Vogel, MD, chief medical officer of Sirion. “In the U.S. trial, difluprednate ophthalmic emulsion 0.05% achieved these impressive results when dosed half as frequently as prednisolone acetate ophthalmic suspension 1% and may potentially provide clinicians with a more powerful and convenient treatment for uveitis.”

The recommended dosage of difluprednate for the treatment of postoperative inflammation and pain associated with ocular surgery is one drop instilled into the conjunctival sac of the affected eye four times daily, beginning 24 hours after surgery, and continuing for 2 weeks postoperatively. The regimen should be followed by twice-daily dosing for 1 week, with tapering based on patient response, according to the company.

Difluprednate is contraindicated in patients with viral diseases of the cornea and conjunctiva and in patients with fungal or mycobacterial infections of the eye or ocular structures. The most common ocular adverse reactions in patients treated with difluprednate included corneal edema, ciliary and conjunctival hyperemia, eye pain, photophobia, posterior capsule opacification, anterior chamber cells, anterior chamber flare, conjunctival edema, and blepharitis.

The FDA has issued an action date of Oct. 24 for the supplemental NDA.