Sirion Therapeutics, Inc. announced today that its supplemental New Drug Application (sNDA) submitted to the U.S. Food and Drug Administration (FDA) seeking market approval of Durezol(TM) (difluprednate ophthalmic emulsion) 0.05% to treat endogenous anterior uveitis has been accepted for review.
Durezol, developed and marketed by Sirion Therapeutics, was approved by the FDA in June 2008 for the treatment of post-operative inflammation and pain associated with ocular surgery.
"Uveitis is a debilitating and painful condition, and is one of the leading causes of blindness in the US," said Barry Butler, CEO of Sirion Therapeutics. "We are encouraged that the FDA is reviewing the application for our drug, which has the potential to treat this sight threatening condition."
The supplemental application includes data from several clinical studies, including one recently completed trial in the US of 90 patients with endogenous anterior uveitis that compared Durezol dosed QID to Pred Forte(R) (prednisolone acetate ophthalmic suspension) 1%, Allergan, dosed 8 times a day. In this study, Durezol was found to be non-inferior to Pred Forte in reducing the mean anterior chamber cell grade at Day 14 (mean cell grade reduction of 2.1 compared to 1.9). In addition, Durezol was numerically superior in almost every efficacy measure, including the reduction of anterior chamber flare and the reduction of signs and symptoms of inflammation. Notably, 12.5% of patients in the Pred Forte group were withdrawn from the trial due to lack of efficacy, while no patients were withdrawn from the Durezol group for this reason.
Two phase 3 clinical trials, conducted in Japan by Senju Pharmaceuticals, Ltd, were also part of the application. In one trial of 136 patients with anterior uveitis and panuveitis, those treated with Durezol QID had a significantly greater improvement on Day 7 compared to those treated with betamethasone ophthalmic solution, 0.1% QID on the measures of anterior chamber cell score and total sign score. Betamethasone is a strong steroid approved outside of the US to treat ocular inflammation. In another trial of 19 patients with severe endogenous anterior uveitis and panuveitis (more than 50 anterior chamber cells) that did not respond to previous therapies, Durezol QID was effective in reducing anterior chamber cell, flare, and total sign and symptom scores. After 14 days of Durezol treatment, 72% of patients had less than 10 cells and 11% had no cells in the anterior chamber.
In the US and Japanese uveitis trials mentioned above, adverse events were generally mild to moderate. In the US trial, clinically significant IOP rise (a rise of greater than or equal to 10 mm Hg from baseline with an observed pressure of greater than or equal to 21 mm Hg) was 6% for Durezol QID and 5% for Pred Forte. In the larger Japanese trial for anterior uveitis, the clinically significant IOP rise for Durezol QID and betamethasone QID was 2.9% and 3%, respectively. In the Japanese trial for severe refractory anterior uveitis, the clinically significant IOP rise for Durezol QID was 5.3%.
"The studies included in this application demonstrate the efficacy of Durezol in quickly resolving uveitis, a disease state in which prompt eradication of inflammation is key in preserving vision," stated Roger Vogel, MD, Chief Medical Officer of Sirion Therapeutics. "In the U.S. trial, Durezol achieved these impressive results when dosed half as frequently as Pred Forte, and may potentially provide clinicians with a more powerful and convenient treatment for uveitis."
The FDA has issued an action date of October 24, 2009 for the supplemental NDA.
About Uveitis
Uveitis is inflammation of the middle three layers of the eye: iris, choroid, and ciliary body. The most common form of the condition is anterior uveitis, associated primarily with inflammation of the iris. If left untreated or under treated, uveitis can cause permanent damage and vision loss due to the development of glaucoma, cataract, or retinal edema. In addition to potential vision loss, the severe pain and photophobia that accompany anterior uveitis can be debilitating.
About Durezol