Allergan, Inc. (NYSE:AGN) announced that the U.S. Food and Drug Administration has approved COMBIGAN™ (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5%, an alpha adrenergic receptor agonist with a beta adrenergic receptor inhibitor, for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP. COMBIGAN™ is the newest addition to Allergan’s comprehensive glaucoma portfolio, which also includes LUMIGAN® (bimatoprost ophthalmic solution) 0.03% and ALPHAGAN® P (brimonidine tartrate ophthalmic solution) 0.1% and 0.15%.
“COMBIGAN™ ophthalmic solution is a medication that provides well documented safety and efficacy for patients with inadequately controlled IOP,” said Scott Whitcup, M.D., Allergan’s Executive Vice President, Research and Development. “The development of COMBIGAN™, which has included five key clinical studies, underscores Allergan’s commitment to provide new treatment options for patients with glaucoma.”
COMBIGAN™ is a prescription eye drop that works in two ways to reduce elevated IOP and will be available to physicians in the fourth quarter of 2007. Elevated IOP is a leading risk factor for glaucoma, and the only risk factor that can currently be treated.
“There is no cure for glaucoma; however, lowering elevated IOP can slow the progression of the disease and help prevent further vision loss,” said E. Randy Craven, M.D., Director of Glaucoma Consultants of Colorado and Associate Clinical Professor of Ophthalmology, University of Colorado School of Medicine. “Many patients require more than one medication to meet their target IOP. With COMBIGAN™, it is exciting to be able to offer patients two strong agents in one bottle.”
In the 12-month pivotal trials, COMBIGAN™ significantly reduced mean IOP up to 7.6 mm Hg from baseline and was well tolerated.1 Clinical studies found that COMBIGAN™ ophthalmic solution provided an additional IOP lowering versus either brimonidine or timolol, the two agents included in the formulation of COMBIGAN™, used alone. COMBIGAN™ administered twice a day provided an additional 1 to 3 mm Hg decrease in IOP over brimonidine treatment three times a day and an additional 1 to 2 mm Hg decrease over timolol treatment twice a day. The IOP-lowering of COMBIGAN™ ophthalmic solution dosed twice a day was slightly less than that seen with the concomitant administration of timolol maleate ophthalmic solution 0.5% dosed twice a day and brimonidine tartrate ophthalmic solution 0.2% dosed three times per day.2
Glaucoma, a group of eye diseases characterized by damage to the optic nerve, is a leading cause of preventable blindness in the United States.3 It is estimated that more than three million Americans have glaucoma, but only half of those know they have it.4 The total number of glaucoma cases worldwide is estimated to be 65 million.4 One of the risk factors of glaucoma is elevated IOP, or pressure inside the eye. A healthy eye produces fluids, called aqueous humor, at the same rate fluids are drained. If the aqueous humor is not removed rapidly enough or too rapidly, pressure builds up in the eye, which can result in glaucoma. This high pressure distorts the shape and damages the optic nerve. Maintaining healthy IOP levels may slow the progression of the disease and help prevent loss of vision.
Important Safety Information:
Contraindications: COMBIGAN™ ophthalmic solution is contraindicated in patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease; in patients with sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, cardiogenic shock; and in patients with hypersensitivity to any component of this product.
Warnings and Precautions: Severe respiratory reactions including death due to bronchospasm in patients with asthma have been reported following systemic or ophthalmic administration of timolol maleate. Sympathetic stimulation may be essential in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe cardiac failure. In patients without a history of cardiac failure, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. Patients with chronic obstructive pulmonary disease (e.g., chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease should, in general, not receive beta-blocking agents, including COMBIGAN™. COMBIGAN™ may potentiate syndromes associated with vascular insufficiency. While taking beta-blockers, patients may be more reactive to allergens. Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms. Beta-adrenergic receptor blocking agents may mask hypoglycemic symptoms in patients with diabetes mellitus. Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents that might precipitate a thyroid storm.
Adverse reactions: The most common adverse reactions occurring in approximately 5 to 15 percent of patients included allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, and ocular burning and stinging.
About Allergan, Inc.
With more than 55 years of experience providing high-quality, science-based products, Allergan, Inc., with headquarters in Irvine, California, discovers, develops and commercializes products in the ophthalmology, neurosciences, medical dermatology, medical aesthetics, obesity intervention, urologics and other specialty markets that deliver value to its customers, satisfy unmet medical needs, and improve patients’ lives.
This press release contains “forward-looking statements”, including the statements by Dr. Whitcup and Dr. Craven and other statements regarding research and development outcomes, efficacy, market and product potential and other statements regarding COMBIGAN™. 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 new product marketing, such as the unpredictability of market acceptance for new pharmaceutical and biologic products and/or the acceptance of new indications for such products; inconsistency of treatment results among patients; potential difficulties in manufacturing a new product formulation; 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 2006 Form 10-K and Allergan’s Form 10-Q for the quarter ended June 29, 2007. Copies of Allergan’s press releases and additional information about Allergan is available on the World Wide Web at allergan.
1 Sherwood MB, Craven ER, Chou C, et al. Twice-daily 0.2% brimonidine-0.5%/timolol fixed-combination therapy vs monotherapy with timolol or brimonidine in patients with glaucoma and ocular hypertension: a 12-month randomized trial. Arch Ophthalmol. 2006; 124(9): 1230-1238.
2 COMBIGAN™ prescribing information.
3 Eyecare America; The Foundation of the American Academy of Ophthalmology. “Facts About Blindness and Eye Health.” Available here. Accessed October 30, 2007.
4 Glaucoma Research Foundation. “Glaucoma Facts and Stats” Available here. Accessed October 16, 2007.
View drug information on Alphagan; Lumigan.