Sirion Therapeutics Announces Positive Phase III Results forDifluprednate- Data Support NDA Submission -
TAMPA, Fla., October 25, 2007 /PRNewswire-FirstCall/ -- Sirion Therapeutics, Inc., a privately held ophthalmic-focused biopharmaceutical company, announced positive preliminary results from its Phase III difluprednate (ST-601) program, which evaluated the steroid's potential to rapidly resolve inflammation in the eye following ocular surgery.
"We are very pleased with the data that demonstrate difluprednate's potential as a potent, well-tolerated steroid treatment for post-operative inflammation," said Dr. Roger Vogel, Sirion's Chief Medical Officer. "Based on these data, Sirion is moving forward with its plans to submit a New Drug Application to the FDA."
The Phase III program consisted of two multi-center, randomized, double- masked studies that compared the safety and efficacy of difluprednate 0.05% to placebo, dosed two (BID) or four (QID) times daily beginning 24 hours after surgery. The studies included 439 subjects who presented with Grade 2 (an inflammatory cell count greater than or equal to 10) or higher the day after surgery. Inflammation was measured by the number of cells in the anterior chamber of the eye with a Grade 0 equaling less than or equal to one cell. The primary efficacy endpoint measured the proportion of subjects whose inflammation reached Grade 0 at Day 8.
Both difluprednate dosing regimens were superior to placebo at the primary endpoint, reaching high statistical significance at Day 8 and maintaining superiority through both the treatment period (Day 15) and the tapering period (Day 29). At Day 15, 56% of subjects on the BID regimen reached Grade 0 compared to 16% in the control group (p<0.0001). Of the subjects on the QID regimen, 63% reached Grade 0 at Day 15. This was also statistically significant when compared to placebo, but not clinically different than the BID regimen. In addition, both difluprednate groups were statistically better than placebo in eliminating pain as measured using the Visual Analogue Scale.
Recent studies in post-operative inflammation have used "clinical cure" at Day 15 as the primary endpoint. In these studies, clinical cure was defined as having 5 anterior chamber cells or less and a flare score of zero. Applying these criteria to our data, at Day 15, 73% of subjects on the difluprednate BID regimen reached clinical cure versus 27% of subjects in the placebo group, for a treatment effect of 46% (p<0.0001). In the difluprednate QID group, 71% of subjects reached clinical cure at Day 15.
Difluprednate was well tolerated with few treatment related adverse events. Of particular note, mean intraocular pressure (IOP) for all study groups remained within the normal range throughout the trial. Three subjects (3%) in the BID group, three subjects (3%) in the QID group, and two subjects (1%) in the placebo group met the criterion for a clinically significant rise in IOP, defined as an increase of greater than 10 mmHg from baseline combined with a peak pressure of more than 21 mmHg at any time point during the study period.
The analysis demonstrated comparable clinical efficacy and acceptable safety profiles for both BID and QID dosing of difluprednate.
"These are extremely robust data," said Dr. Michael Korenfeld, an ophthalmologist with Comprehensive Eye Care in Washington, Missouri who was an investigator in the trial. "Being able to treat ocular inflammatory disease with a more convenient dosing regimen and having the potential to offer rapid resolution of inflammation after ocular surgery would represent a meaningful advance for patients."
"Sirion is very excited about these results. When we started this program, we felt that difluprednate had the potential to be a major step forward in the control of ocular inflammation. These results met our highest expectations" said Barry Butler, President and CEO of Sirion. "We look forward to bringing this important new treatment option to ophthalmologists and patients."
About Post-Operative Inflammation
There are more than 3.5 million ophthalmic surgeries performed each year in the United States. Post-operative inflammation is a common occurrence following these procedures. While it tends to be self-resolving, some cases can lead to serious sequelae. If left untreated, inflammation following ocular surgery can interfere with the patient's visual rehabilitation or lead to further complications, such as acute pain and discomfort, chronic cystoid macular edema, posterior capsule fibrosis, keratopathy, fibrin reaction, or chronic uveitis. As there is no way to predict which patients might develop inflammatory complications, doctors often prescribe steroids and/or NSAID drops. Most often, post-operative inflammation lasts a relatively short time, though severe forms of inflammation can persist for a longer period of time.
About Difluprednate (ST-601)
Difluprednate is a potent ophthalmic steroid emulsion that has the potential to treat patients suffering from ocular inflammatory disease. Difluprednate's unique formulation permits rapid penetration of the cornea, which promotes quick resolution of anterior chamber cells and flare. A Phase 3 program evaluating difluprednate in patients with post-surgical inflammation was completed in September of 2007, showing difluprednate's potential to rapidly eradicate ocular inflammation versus placebo while maintaining an acceptable safety profile. In addition to post-surgical inflammation, difluprednate is being evaluated in a Phase 3 program as a treatment for patients with uveitis.
About Sirion Therapeutics, Inc.
Sirion Therapeutics is a privately held biopharmaceutical company pursuing the discovery, development and commercialization of products addressing unmet medical needs in the protection and preservation of eyesight. Sirion's pipeline includes four late-stage opportunities: ganciclovir, a topical antiviral for herpetic keratitis with a planned NDA submission in early 2008; difluprednate, a potent topical steroid in Phase III development for post- operative inflammation and uveitis; cyclosporine, a topical immunomodulator in Phase III testing for dry eye and fenretinide, a first-in-class oral vitamin A binding protein antagonist in Phase II development for geographic atrophy associated with dry AMD. In addition, Sirion plans to leverage its expertise in ophthalmology and vision research to identify additional candidates in back of the eye diseases, through both internal research efforts and partnering opportunities.
Posted: October 2007