Allergan, Inc. (NYSE: AGN) announced that the United States Food and Drug Administration (FDA) has approved OZURDEX(R) (dexamethasone intravitreal implant) 0.7 mg for the treatment of non-infectious ocular inflammation, or uveitis, affecting the posterior segment of the eye. Uveitis is characterized by inflammation of the eye’s uvea, which is the middle vascular layer consisting of the iris (anterior), ciliary body (intermediate) and choroid (posterior). Uveitis of the anterior (front) of the uvea is more common and typically does not lead to vision impairment;1 while posterior uveitis (back of the eye) is associated with more severe outcomes that can include blindness, cataracts, secondary glaucoma and macular abnormalities.2 Posterior uveitis is the cause of 10 to 15 percent of cases of blindness in the United States.3 OZURDEX(R) is a biodegradable implant that delivers an extended release of the corticosteroid dexamethasone via intravitreal injection with Allergan’s proprietary and innovative NOVADUR(R) solid polymer delivery system.
The efficacy of OZURDEX(R) for the treatment of non-infectious uveitis affecting the posterior segment of the eye was assessed in a 26-week, multi-center, double-masked, randomized clinical study in which 77 patients received OZURDEX(R) 0.7 mg and 76 patients received sham injections. Eligible patients had non-infectious ocular inflammation of the posterior segment with intermediate or posterior uveitis, a vitreous haze grade of >+1 on the 0-4 classification scale and best corrected visual acuity (BCVA) of 10 to 75 letters on the Snellen eye chart. In terms of vitreous haze, a score of +1 on the scale indicates slightly blurred optic nerve and vessels. Severity increases with each grade of the scale, with grade 4 indicating that the optic nerve head is obscured. Key exclusion criteria included history of glaucoma or use of intraocular pressure (IOP) lowering medications within the last month.
After a single injection of OZURDEX(R), the percent of patients reaching a vitreous haze score of zero (where a score of zero represents no inflammation) was statistically significantly greater for patients in the OZURDEX(R) treated group versus sham (47 versus 12 percent, respectively) at the week eight primary endpoint. In addition, the percent of patients achieving a 3-line improvement in BCVA was 43 percent in the OZURDEX(R) treated group, versus seven percent for the sham group at week eight.
“The approval of OZURDEX(R) offers physicians another option to treat ocular inflammation resulting from uveitis affecting the posterior segment of the eye,” said Scott Whitcup, M.D., Allergan’s Executive Vice President, Research and Development and Chief Scientific Officer. “It is also a milestone for Allergan’s Retina franchise, which exemplifies our continued commitment to developing and bringing to market advanced therapies that meet the unmet medical needs of patients with difficult-to-treat retinal diseases.”
OZURDEX(R) is administered as an in-office procedure. The treatment is currently available to physicians and patients in the United States and the European Union. OZURDEX(R) implants were initially approved in June 2009 as the first drug therapy indicated for the treatment of macular edema following retinal vein occlusion (RVO).
About Non-Infectious Uveitis Affecting the Posterior Segment of the Eye
Symptoms of uveitis affecting the posterior segment of the eye may include photopsia (perceived flashes of light), floaters (appearing as spots or threads), scotomata (area of diminished vision), and metamorphopsia (vision distortion),4 which lead to vitreous haze and loss of BCVA. Uveitis causes an estimated 10 to 15 percent or more of cases of blindness in the United States; the large majority of these cases occur in people between the ages of 20 to 60 years old, usually in their 30s and 40s.5
More severe cases of non-infectious intermediate, and most cases of non-infectious posterior uveitis, are typically treated with local and systemic steroids, along with immunosuppressives in certain cases.6 Tablets or injections are needed to deliver the drug effectively to the middle and back of the eye. However, steroids that are administered systemically for a prolonged period may have potential serious systemic side effects that can limit use of the drugs.7
INDICATIONS AND USAGE
OZURDEX(R) (dexamethasone intravitreal implant) 0.7 mg
Retinal Vein Occlusion
Ozurdex(R) (dexamethasone intravitreal implant) is indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).
Posterior Segment Uveitis
Ozurdex(R) is indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye.
DOSAGE AND ADMINISTRATION
FOR OPHTHALMIC INTRAVITREAL INJECTION ONLY.
The intravitreal injection procedure should be carried out under controlled aseptic conditions. Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis without delay.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Ocular or Periocular Infections
Ozurdex(R) (dexamethasone intravitreal implant) is contraindicated in patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.
Advanced Glaucoma
Ozurdex(R) is contraindicated in patients with advanced glaucoma.
Hypersensitivity
Ozurdex(R) is contraindicated in patients with known hypersensitivity to any components of this product
WARNINGS AND PRECAUTIONS
Intravitreal Injection-related Effects
Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored following the injection.
Potential Steroid-related Effects
Use of corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses.
Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex.
ADVERSE REACTIONS
The most common ocular adverse reactions reported by greater than 2% of patients in the first 6 months following injection of Ozurdex(R) for retinal vein occlusion and posterior segment uveitis include: intraocular pressure increased (25%), conjunctival hemorrhage (22%), eye pain (8%), conjunctival hyperemia (7%), ocular hypertension (5%), cataract (5%), vitreous detachment (2%), and headache (4%).
Increased IOP with Ozurdex(R) peaked at approximately week 8. During the initial treatment period, 1% (3/421) of the patients who received Ozurdex(R) required surgical procedures for management of elevated IOP.
Forward-Looking Statements
This press release contains “forward-looking statements,” including the statements by Dr. Whitcup and other statements regarding research and development outcomes, efficacy, adverse reactions, market and product potential, product availability and other statements regarding OZURDEX(R) for the treatment of noninfectious ocular inflammation due to intermediate or posterior uveitis implant. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Allergan’s expectations and projections. Risks and uncertainties include, among other things, general industry and pharmaceutical market conditions; technological advances and patents attained by competitors; challenges inherent in the research and development and regulatory processes; challenges related to product marketing, such as the unpredictability of market acceptance for new pharmaceutical products and/or the acceptance of new indications for such products; inconsistency of treatment results among patients; potential difficulties in manufacturing a new product; general economic conditions; and governmental laws and regulations affecting domestic and foreign operations. Additional information concerning these and other risk factors can be found in press releases issued by Allergan, as well as Allergan’s public periodic filings with the Securities and Exchange Commission, including the discussion under the heading “Risk Factors” in Allergan’s 2009 Form 10-K and Allergan’s quarterly reports on Form 10-Q for the quarters ended March 31, 2010 and June 30, 2010.
© 2010 Allergan, Inc. Irvine, CA 92612. (R) marks owned by Allergan, Inc.
References
(1) M S A Suttorp-Schulten, A Rothova, The possible impact of uveitis in blindness: a literature survey. British Journal of Ophthalmology 1996;80:844-848.
(2) M S A Suttorp-Schulten, A Rothova, The possible impact of uveitis in blindness: a literature survey. British Journal of Ophthalmology 1996;80:844-848.
(3) M S A Suttorp-Schulten, A Rothova, The possible impact of uveitis in blindness: a literature survey. British Journal of Ophthalmology 1996;80:844-848.
(4) AT Gerstenblith et al. Punctate inner choroidopathy: a survey analysis of 77 persons. Ophthalmology. 2007 Jun;114(6):1201-4. Epub 2007 Apr 16.
(5) M S A Suttorp-Schulten, A Rothova, The possible impact of uveitis in blindness: a literature survey. British Journal of Ophthalmology 1996;80:844-848.
(6) S Sudharshan et al. Current approach in the diagnosis and management of posterior uveitis. Indian J Ophthalmol. 2010 Jan-Feb; 58(1): 29-43.
(7) FR Zakka et al. Current trends in the management of ocular symptoms in Adamantiades-Beh?�et’s disease. Clinical Ophthalmology. Oct 15 2009
Source: Allergan, Inc