Charles Runels, MD
COMMENTING ON THE U.S. FOOD AND DRUG ADMINISTRATION (FDA) EARLY COMMUNICATION, ALLERGAN CLARIFIES FDA’S INQUIRY RELATES PRIMARILY TO HIGH DOSE MEDICAL USES OF BOTOX®, RATHER THAN
BOTOX® COSMETIC FOR AESTHETIC USE
(IRVINE, Calif., February 8, 2008) – Allergan, Inc. (NYSE: AGN) today commented on and provided support for the U.S. Food and Drug Administration’s (FDA) “Early Communication” regarding a safety review of botulinum toxins in the United States.
BOTOX® (botulinum toxin type A) is indicated and used to treat a variety of often serious medical conditions, and BOTOX® Cosmetic is approved by the FDA for the aesthetic treatment of wrinkles between the brows and involves very different doses.
The FDA announced this morning in an “Early Communication” that it was reviewing certain serious adverse events following the use of botulinum toxins, particularly for the management of juvenile cerebral palsy. This posting of an “Early Communication” is a routine protocol used by the FDA to provide early information regarding safety or other related reviews, often before any conclusions are or can be made. Specifically, the FDA made clear in its communication that “the posting of this information does not mean that there is a causal relationship between the products and the adverse events.”
Importantly, the FDA hosted a public teleconference this afternoon in which it provided helpful clarification and context, explaining that this review involves only “a relative handful of serious adverse events” and that the primary focus of the adverse events and the FDA’s review of them related to the therapeutic use of BOTOX® to treat juvenile cerebral palsy and other large muscle, lower limb spasticities.
While the use of BOTOX® for the treatment of juvenile cerebral palsy is approved in approximately 60 countries and has been used by health care practitioners in the United States for well over a decade, it is not currently an FDA-approved use of the product in the United States. As the FDA confirmed in its public teleconference today, however, the off-label use of the product in the United States for this ailment is left to the medical judgment of the health care practitioner and the FDA’s current review should not be interpreted to mean that the FDA is suggesting that this particular use is inappropriate.
With respect to the therapeutic use of BOTOX® to treat juvenile cerebral palsy and other lower limb spasticities, one should keep in mind that the population, treatment paradigms and typical dosing of product is significantly greater than some of the other approved uses of the product, including specifically the FDA-approved use of BOTOX® Cosmetic to treat wrinkles between the brows.
In particular, the FDA on its teleconference pointed out that this population of patients tends to be “very sick” and that, sadly, this population is generally subject to greater than usual serious adverse events and a higher mortality rate than a healthy population, regardless of the use of the product.
Additionally, in actual practice the treatment of juvenile cerebral palsy tends to involve large lower limb muscles and the amount of BOTOX® used is typically far greater than the FDA-approved dosing for BOTOX® Cosmetic. In its “Early Communication,” the FDA reported dose in the serious adverse events “ranged from 100 to 700 units” while the approved dosing for BOTOX® Cosmetic is 20 units. The difference is higher still on a per-kilogram of body weight basis, as this population often involves young and lower weight patients than the generally healthy adult population seeking a BOTOX® Cosmetic treatment.
Importantly, the FDA confirmed in the teleconference that none of the adverse events that are the subject of its review relate to a death involving the use of BOTOX® Cosmetic for an aesthetic use. The FDA’s conclusion is consistent with Allergan’s safety analysis. “Since its approval, over a million people have been treated with BOTOX® Cosmetic. In its entire history, there has never been a single reported death where a causal link to BOTOX® Cosmetic was established,” said Dr. Sef Kurstjens, Allergan’s Chief Medical Officer.
Allergan fully supports the FDA’s safety review of these adverse event reports and is working with the FDA to ensure that it has all of the information necessary to make an informed and reasonable judgment regarding them. Additionally, Allergan appreciates the FDA’s willingness to provide a public teleconference to place its review into its proper context.
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Important BOTOX® and BOTOX® Cosmetic (Botulinum Toxin Type A) Information
BOTOX® is indicated for the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia.
BOTOX® is also indicated for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and above.
The efficacy of BOTOX® treatment in deviations over 50 prism diopters, in restrictive strabismus, in Duane’s syndrome with lateral rectus weakness, and in secondary strabismus caused by prior surgical over-recession of the antagonist has not been established. BOTOX® is ineffective in chronic paralytic strabismus except when used in conjunction with surgical repair to reduce antagonist contracture.
And BOTOX® is indicated for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents.
BOTOX® Cosmetic is approved for the temporary treatment of moderate to severe frown lines between the brows in people ages 18-65.
Important BOTOX® and BOTOX® Cosmetic (Botulinum Toxin Type A) Safety Information
BOTOX® and BOTOX® Cosmetic treatment should not be injected in the presence of infection at the proposed injection site(s) and in individuals with known hypersensitivity to any ingredient in the formulation.
Serious heart problems and serious allergic reactions have been reported rarely. If you think you’re having an allergic reaction or other unusual symptoms, such as difficulty swallowing, speaking or breathing, call your doctor immediately. Individuals with peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis, or motor neuropathy) or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) should only receive BOTOX® or BOTOX® Cosmetic with caution. Patients with neuromuscular disorders may be at increased risk of clinically significant systemic side effects with BOTOX® or BOTOX® Cosmetic. For full prescribing information, please visit www.botox.com and www.botoxcosmetic.com.
BOTOX® for Blepharospasm in Patients > 12 Years of Age: Reduced blinking from BOTOX® injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect and corneal perforation. The most frequently reported treatment-related adverse reactions in these patients are ptosis (20.8%), superficial punctate keratitis (6.3%) and eye dryness (6.3%).
BOTOX® for Strabismus in Patients > 12 Years of Age: Inducing paralysis in one or more extraocular muscles may produce spatial disorientation, double vision or past pointing. The most commonly reported adverse effects are ptosis (16%) and vertical deviation (17%).
BOTOX® for Cervical Dystonia in Adults: There have been rare cases of dysphagia severe enough to warrant the insertion of a gastric feeding tube. The most frequently reported adverse reactions in patients with cervical dystonia are dysphagia (19%), upper respiratory infection (12%), neck pain (11%), and headache (11%).
BOTOX® for Severe Primary Axillary Hyperhidrosis Inadequately Managed with Topical Agents: The most frequently reported adverse events (3 - 10%) are injection site pain and hemorrhage, non-axillary sweating, infection, pharyngitis, flu syndrome, headache, fever, neck or back pain, pruritus, and anxiety.
BOTOX® Cosmetic for Temporary Improvement in the Appearance of Moderate to Severe Frown Lines Between the Brows in Adults 18-65: The most common side effects following injection include temporary eyelid droop and nausea. Localized pain, infection, inflammation, tenderness, swelling, redness and/or bleeding/bruising may be associated with the injection.
Forward-Looking Statements
This press release contains “forward-looking statements,” including statements regarding the safety, effectiveness and adverse events associated with BOTOX®.
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, biologic and pharmaceutical market conditions; technological advances and patents attained by competitors; challenges inherent in the research and development and regulatory processes; inconsistency of treatment results among patients; potential difficulties in manufacturing; 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 September 28, 2007. Copies of Allergan's press releases and additional information about Allergan is available on the World Wide Web at www.allergan.com or you can contact the Allergan Investor Relations Department by calling 1-714-246-4636.
About Allergan, Inc.
Founded in 1950, Allergan, Inc., with headquarters in Irvine, California, is a multi-specialty health care company that discovers, develops and commercializes innovative pharmaceuticals, biologics and medical devices that enable people to live life to its greatest potential – to see more clearly, move more freely, express themselves more fully. The Company employs more than 7,500 people worldwide and operates state-of-the-art R&D facilities and world-class manufacturing plants. In addition to its discovery-to-development research organization, Allergan has global marketing and sales capabilities with a presence in more than 100 countries.
SOURCE: Allergan, Inc.
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