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Durezol in the Treatment of Uveitis and Ganciclovir in the Treatment of Herpetic Keratitis: Studies of Treatments for Leading Causes of Blindness to Be Presented

TAMPA, Fla., November 03, 2008 /PRNewswire/ -- Sirion Therapeutics, Inc., a privately held ophthalmic-focused biopharmaceutical company, announced today that studies of two investigational drugs in development for treatment of potentially blinding eye diseases will be presented at upcoming ophthalmology meetings: At the American Uveitis Society's annual invitational meeting (November 9, Atlanta Marriott Marquis, Atlanta), preliminary results will be presented from an anterior uveitis trial that compared Sirion's ophthalmic corticosteroid Durezol(TM) (difluprednate ophthalmic emulsion) 0.05% dosed four times daily (QID) to Pred Forte(R)* (prednisolone acetate ophthalmic suspension) 1%, dosed eight times daily. Durezol was approved by the US Food and Drug Administration in June 2008 for the treatment of inflammation and pain associated with ocular surgery.


In addition, data for Sirion's ophthalmic gel formulation of ganciclovir as a treatment for herpetic keratitis will be presented in a poster at the American Academy of Ophthalmology (AAO) Meeting (November 8-11, Atlanta). The poster's author is Herbert E. Kaufman, M.D., Ophthalmologist Emeritus of Sirion Therapeutics and formerly Professor of Ophthalmology and Pharmacology and Head of the Department of Ophthalmology at , and past president of the Association for Research and Vision in Ophthalmology (ARVO), the International Society of Refractive Surgery (ISRS) and the Contact Lens Association of Ophthalmologists (CLAO).

"We're proud to have products in late-stage clinical testing for two of the leading causes of blindness, uveitis and ocular herpes," said Barry Butler, President and CEO of Sirion Therapeutics, Inc. "These medications have the potential to reduce suffering and save the vision of thousands of patient each year, and exemplify our mission to address unmet medical needs in the protection and preservation of eyesight."

The results of the Durezol uveitis study will be presented by investigator Thomas Flynn, M.D., Assistant Professor of Clinical Ophthalmology, , and Ellsworth Uveitis & Retina Care, in his presentation, "Durezol Compared to Pred Forte in the Treatment of Endogenous Anterior Uveitis." The randomized, multicenter, double-masked trial included 90 subjects with endogenous anterior uveitis having greater than 10 cells and a flare score of greater than or equal to 2 in the anterior chamber (AC). In the study, Durezol administered QID was as effective as Pred Forte dosed eight times a day in treating uveitis. Durezol was also safe and well tolerated.

The primary endpoint of the uveitis study was the difference from baseline in AC cell grades between the Durezol and Pred Forte groups. At Day 14, the Durezol group achieved a mean cell grade reduction of 2.1, compared to 1.9 in the Pred Forte group, confirming the noninferiority of Durezol dosed QID to Pred Forte dosed eight times a day.

In addition to reducing mean cell grade, a greater percentage of patients receiving Durezol had an AC cell grade of 0 (less than or equal to 1 cell) than did the Pred Forte group at Day 14 (69% vs. 62%, respectively). This trend continued through Day 42.

Pain/ocular discomfort was assessed using a Visual Analog Scale. Durezol demonstrated a numerical advantage in pain reduction from baseline over Pred Forte at every time point in the study. As early as Day 3, the Durezol group had a reduction in mean pain score of 58% vs. 51% in the Pred Forte group. At Day 7, these were 71% and 64%, respectively.

Two patients in each treatment arm experienced criterion increases in intraocular pressure (defined as a pressure of greater than or equal to 21 mmHg and a change from baseline greater than or equal to 10mmHg at the same visit). Another important safety finding was the number of patients withdrawn from the study due to lack of efficacy. In the Pred Forte group, 12.5% of patients were withdrawn from the study, while no Durezol patients were withdrawn from the study for these reasons. This difference was significant, P=0.01.

Uveitis is responsible for an estimated 30,000 new cases of legal blindness each year in the US and up to 15% of all cases of blindness. The most common form of the condition is anterior uveitis, associated primarily with inflammation of the iris. If left untreated, uveitis can cause debilitating pain and photophobia as well as permanent damage and vision loss due to the development of glaucoma, cataract or retinal edema.

Dr. Kaufman's poster, "Data from Trials Evaluating Ganciclovir Ophthalmic Gel, 0.15% and Acyclovir Ophthalmic Ointment, 3% for Herpetic Keratitis," is part of AAO Poster Session 1 (Sunday, November 09, 11:00 AM - 12:30 PM) on Level 1, Hall B-5. Dr. Kaufman's review of data from three Phase 2 trials and one Phase 3 trial of ganciclovir and acyclovir for herpetic keratitis confirms the efficacy of ganciclovir for treatment of acute herpetic keratitis, as well as better tolerance when compared to acyclovir and low incidence of adverse events.

The efficacy and safety data is from an extensive clinical program conducted outside of the US by Laboratoires Thea of France, with which Sirion Therapeutics has an exclusive licensing agreement for the US rights to develop and market ganciclovir ophthalmic gel, available in Europe for the treatment of ocular viral infections for more than 10 years.

Herpes simplex keratitis is the leading cause of corneal blindness in the US, with 20,000 new primary cases of diagnosed each year and an additional 28,000 cases of recurrence each year. The risk of blindness increases with the number and severity of recurrences, so prompt treatment of herpetic epithelial ulcers is imperative to limit scarring and other more serious complications.

About Durezol

Durezol (difluprednate ophthalmic emulsion) 0.05% is a topical ophthalmic corticosteroid approved for the treatment of inflammation and pain associated with ocular surgery. Difluprednate, the active ingredient in Durezol, is a difluorinated prednisolone derivative that has potent anti-inflammatory activity. Durezol is not approved for the treatment of uveitis.

Important Safety Information

Like other corticosteroids, Durezol is contraindicated in patients with viral diseases of the cornea and conjunctiva, and those with fungal or mycobacterial infections of the eye or ocular structures. Prolonged use of corticosteroids may increase the hazard of secondary ocular bacterial infections, exacerbate the severity of ocular viral infections, and increase the development of fungal infections of the cornea. It is important to monitor intraocular pressure when using ophthalmic steroids. The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.

Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.

Ocular adverse reactions occurring in 5-15% of subjects in clinical studies with Durezol included corneal edema, ciliary and conjunctival hyperemia, eye pain, photophobia, posterior capsule opacification, anterior chamber cells, anterior chamber flare, conjunctival edema, and blepharitis. Other ocular adverse reactions occurring in 1-5% of patients included reduced visual acuity, punctate keratitis, eye inflammation, and iritis. Ocular adverse events occurring in less than 1% of patients included application site discomfort or irritation, corneal pigmentation and striae, episcleritis, eye pruritis, eyelid irritation and crusting, foreign body sensation, increased lacrimation, macular edema, scleral hyperemia, and uveitis. Most of these events may have been the consequence of the surgical procedure.

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 diverse product portfolio includes products that address ocular diseases and conditions including uveitis, herpetic keratitis, dry eye, and geographic atrophy associated with dry AMD.

* Pred Forte is the registered trademark of Allergan, Inc.

Posted: November 2008