Sirion Therapeutics Announces Positive Pivotal Uveitis Data for Durezol(TM)

Wednesday, October 15, 2008 General News
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TAMPA, Fla., Oct. 14 Sirion Therapeutics, Inc., aprivately held ophthalmic-focused biopharmaceutical company, announced todaypreliminary results from a pivotal anterior uveitis trial that comparedDurezol(TM) (difluprednate ophthalmic emulsion) 0.05% dosed four times daily(QID) to Pred Forte(R) (prednisolone acetate ophthalmic suspension) 1%, dosedeight times daily. Durezol is a topical ophthalmic corticosteroid indicatedfor the treatment of inflammation and pain associated with ocular surgery; itwas approved by the US Food and Drug Administration in June 2008. PredForte(R) is the registered trademark of Allergan, Inc.

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Ninety patients with endogenous anterior uveitis were studied in amulticenter, randomized, double-masked trial that compared the efficacy andsafety of Durezol QID with Pred Forte eight times a day. Treatment for bothstudy groups was administered for 14 days, with 2 weeks of tapering at halfthe dose and 2 weeks of follow-up (for a total 42 days) after initiation oftherapy.

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

"This study shows that Durezol is a potent steroid that can be usedeffectively four times a day to reduce inflammation in patients with moderateto severe uveitis," explained C. Stephen Foster, MD, an investigator in thetrial and the founder and president of the Massachusetts Eye Research andSurgery Institution. "This is especially important since the US standard ofcare currently necessitates dosing steroids every hour -- and as frequently asevery 15-30 minutes in more severe cases. In addition, Durezol does notcontain benzalkonium chloride (BAK), a common ocular preservative known tocause corneal toxicity with long-term use. This is especially important forpatients with uveitis, which is a chronic disease. A strong steroid likeDurezol will be a very valuable tool for ophthalmologists everywhere, allowpatients to have an easier dosing regimen, and will most likely become the newstandard of care for treating uveitis."

In addition to reducing mean cell grade, a greater percentage of patientsreceiving 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 trendcontinued through Day 42.

Ocular discomfort and pain is a debilitating symptom of uveitis. In thisstudy, pain was assessed using a Visual Analog Scale. Durezol demonstrated anumerical advantage in pain reduction from baseline over Pred Forte at everytime point in the study. As early as Day 3, the Durezol group had a reductionin mean pain score of 58% vs 51% in the Pred Forte group. At Day 7, thesewere 71% and 64%, respectively.

Durezol was also very effective in reducing the symptoms of anteriorocular inflammation (pain/ocular discomfort, photophobia, blurred vision, andlacrimation). The Durezol group achieved a mean reduction in total symptomscore of 76% vs 71% for Pred Forte at Day 14. This numerical difference wasmaintained through Day 42 with the Durezol group reducing the total symptomscore by 86% vs 76% for the Pred Forte group.

The total sign score was also reduced to a greater degree in the Durezolgroup when compared to the Pred Forte group: 6.5 vs 6.1 at Day 14,respectively. Total sign score included the sums of posterior synechiae,hypopyon, limbal injection, peripheral anterior synechiae, AC flare, AC celland keratic precipitate grades. The numerical advantage of Durezol over PredForte in total sign score continued throughout the study period.

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

The results from this study will be combined with data from previoustrials conducted in Japan to support a supplemental New Drug Application foranterior uveitis. "The results of these trials are truly exciting," notedBarry Butler, CEO and President of Sirion Therapeutics. "Although this studywas not designed to detect the statistical superiority of one drug over theother, the consistent numerical advantage of Durezol across all endpoints isimpressive. This is especially so, when you consider that Pred Forte has 20times the concentration of Durezol and was dosed twice as often. This clearlydemonstrates the potency of Durezol."

About Uveitis

Uveitis is inflammation of the middle three layers of the eye: iris,choroid, and ciliary body. In the US it is responsible for an estimated 30,000new cases of legal blindness each year and up to 15% of all cases of blindness.It affects 0.2% of the population in industrial nations, with as much as 10times that prevalence in the undeveloped world. The most common form of thecondition is anterior uveitis, associated primarily with inflammation of theiris. If left untreated, uveitis can cause permanent damage and vision lossdue to the development of glaucoma, cataract, or retinal edema. In addition tocausing blindness, the severe pain and photophobia that accompany anterioruveitis can be debilitating.

About Durezol

Durezol (difluprednate ophthalmic emulsion) 0.05% is a topical ophthalmiccorticosteroid approved for the treatment of inflammation and pain associatedwith ocular surgery. Difluprednate, the active ingredient in Durezol, is adifluorinated prednisolone derivative that has potent anti-inflammatoryactivity. Prior to US approval, the efficacy and safety of difluprednate dosedfour times a day in ocular inflammatory diseases had been demonstrated in anextensive preclinical and clinical program in Japan, including two studies inanterior uveitis and one in refractory uveitis. In two US Phase 3 trialsevaluating Durezol in patients diagnosed with significant postoperativeinflammation (more than 10 anterior chamber cells), Durezol effectivelyreduced inflammation and pain.

Dosage and Administration

The recommended dosage and administration of Durezol in the treatment ofpostoperative inflammation and pain is to instill one drop into theconjunctival sac of the affected eye(s) 4 times daily beginning 24 hours aftersurgery and continuing throughout the first 2 weeks of the postoperativeperiod, followed by 2 times daily for a week with tapering based on theresponse.

Important Safety Information

Like other corticosteroids, Durezol is contraindicated in patients withviral diseases of the cornea and conjunctiva, and those with fungal ormycobacterial infections of the eye or ocular structures. Prolonged use ofcorticosteroids may increase the hazard of secondary ocular bacterialinfections, exacerbate the severity of ocular viral infections, and increasethe development of fungal infections of the cornea. It is important to monitorintraocular pressure when using ophthalmic steroids. The use of steroids aftercataract surgery may delay healing and increase the incidence of blebformation.

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

Ocular adverse reactions occurring in 5-15% of subjects in clinicalstudies with Durezol included corneal edema, ciliary and conjunctivalhyperemia, eye pain, photophobia, posterior capsule opacification, anteriorchamber cells, anterior chamber flare, conjunctival edema, and blepharitis.Other ocular adverse reactions occurring in 1-5% of patients included reducedvisual acuity, punctate keratitis, eye inflammation, and iritis. Ocularadverse events occurring in < 1% of patients included application sitediscomfort or irritation, corneal pigmentation and striae, episcleritis, eyepruritis, eyelid irritation and crusting, foreign body sensation, increasedlacrimation, macular edema, scleral hyperemia, and uveitis. Most of theseevents may have been the consequence of the surgical procedure.

About Sirion Therapeutics, Inc.

Sirion Therapeutics is a privately held biopharmaceutical company pursuingthe discovery, development, and commercialization of products addressing unmetmedical needs in the protection and preservation of eyesight. Sirion's diverseproduct portfolio includes products that address ocular diseases andconditions including uveitis, herpetic keratitis, dry eye, and geographicatrophy associated with dry AMD. For more information, please visit

SOURCE Sirion Therapeutics, Inc.

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