IRVINE, Calif.--(BUSINESS WIRE)--Allergan, Inc. (NYSE:AGN - News) today announced it has received a complete response letter from the U.S. Food and Drug Administration (FDA) regarding the Company’s Supplemental Biologics License Application (sBLA) for BOTOX® (Botulinum Toxin Type A) to treat upper limb spasticity in post-stroke adults. Allergan submitted its sBLA for this indication in the third quarter of 2008.
The FDA has not requested additional pre-approval clinical studies. However, the FDA has identified items that must be completed before the sBLA can be considered for approval, including the following:
1. Risk Evaluation and Mitigation Strategy (REMS) and Safety Update:
On April 29, 2009, the FDA approved DYSPORT™ (abobotulinumtoxinA) for the treatment of cervical dystonia in adults and the temporary improvement in the appearance of moderate to severe glabellar lines in adults younger than 65 years of age and imposed a REMS for that product. Concurrently, the FDA requested that Allergan adopt a substantially similar REMS for BOTOX®. Allergan has submitted its proposed REMS for the FDA’s review. The FDA indicated that it had not yet reviewed Allergan’s submission and that an approved REMS will be necessary prior to approving BOTOX® to treat upper limb spasticity. Also, the FDA requested that in its reply to the complete response letter, Allergan provide a product safety update from clinical and non-clinical studies across indications.
2. Source Data Documentation:
While the FDA’s complete response letter acknowledges that the sBLA supports the efficacy and safety of BOTOX® for the treatment of upper limb spasticity, the FDA has requested that Allergan independently verify underlying patient source documentation at study sites relating to one of the pivotal clinical studies conducted in 1999 and upon completion of the verification, provide an updated analysis. In the sBLA, Allergan submitted data from 16 studies including an integrated analysis of 7 double-blind, placebo-controlled trials.
Allergan estimates that the re-verification can be completed and the analysis submitted to the FDA in approximately 60 to 90 days.
3. Product Labeling:
In its complete response letter, the FDA proposed revisions to Allergan’s proposed labeling, including enhanced safety information and other clarifications. Among other revisions, the FDA proposed a revised spasticity indication. In its sBLA, Allergan proposed the use of BOTOX® for the treatment of upper limb spasticity associated with stroke. In its complete response letter, the FDA noted the focal nature of BOTOX® treatments and the similarities of spasticity across conditions and thus proposed revised labeling that would broaden the indication of use to upper limb spasticity regardless of underlying cause. Also, noting the number of pediatric patients such as those with juvenile cerebral palsy who suffer from upper limb spasticity, the FDA requested that Allergan conduct a post-approval study for BOTOX® to treat upper limb spasticity in pediatric patients 2-17 years of age. This request is consistent with Allergan’s proposal in connection with the submission of its proposed REMS and Allergan hopes to discuss with the FDA a protocol that, if successful, would support an approval for the treatment of children suffering from spasticity.
Allergan will diligently respond to the FDA’s proposed label revisions and will develop a pediatric plan to further study BOTOX® in children.
“A significant unmet medical need for those suffering from upper limb spasticity exists in the United States. It is estimated that nearly 500,000 Americans each year develop stroke-related spasticity, the majority of which includes upper limb spasticity1,2. And yet about half of those patients receive no treatment for their spasticity,” said Scott Whitcup, M.D., Executive Vice President, Research & Development, Chief Scientific Officer, Allergan, Inc. “We have already submitted our REMS for BOTOX® as we anticipated this requirement as a condition to an approved spasticity indication. We will work expeditiously to provide the FDA with all other information requested in the complete response letter to support a rapid final review of our application for BOTOX® as a treatment for upper limb spasticity.”
About BOTOX®
BOTOX® is a prescription-only medical product that contains tiny amounts of highly purified botulinum toxin protein refined from the bacterium, Clostridium botulinum. When injected at approved and labeled doses into a specific muscle or gland, BOTOX® is expected to diffuse locally and expected to produce a safe and effective result by producing a localized and temporary reduction in the overacting muscle or gland, usually lasting between 3 and 6.7 months depending on the individual patient and indication.
BOTOX® was first approved by the FDA nearly twenty years ago for the treatment of strabismus and blepharospasm, two eye muscle disorders, making it the first botulinum toxin type A product approved in the world. Since its first approval, BOTOX® has been recognized by regulatory authorities worldwide as an effective treatment for 21 different indications in approximately 80 countries, benefiting millions of patients worldwide. In the United States, BOTOX® is also approved for the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with the disorder, and for the treatment of severe primary axillary hyperhidrosis (excessive underarm sweating) that is inadequately managed with topical agents. In addition to its therapeutic uses, the same formulation of BOTOX® with dosing specific to glabellar lines was approved by the FDA in 2002 under the trade name BOTOX® Cosmetic.
In addition to nearly 20 years of clinical experience, the safety and efficacy of BOTOX® have been well-established in approximately 50 randomized, placebo-controlled clinical trials and in approximately 11,000 patients treated with BOTOX® and BOTOX® Cosmetic in Allergan’s clinical trials3.
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.
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.
Additional Important Safety Information
The FDA on April 30, 2009, in its update to the early communication sent in 2008, gave the following recommendations:
* Understand that dosage strength (potency) expressed in “Units” or “U” are different among the botulinum toxin products; clinical doses expressed in units are not interchangeable from one botulinum toxin product to another. * Be alert to and educate patients and caregivers about potential adverse events due to distant spread of botulinum toxin effects following local injections including: unexpected loss of strength or muscle weakness, hoarseness or trouble talking (dysphonia), trouble saying words clearly (dysarthria), loss of bladder control, trouble breathing, trouble swallowing, double vision, blurred vision and drooping eyelids. * Understand that these adverse events have been reported as early as several hours and as late as several weeks after treatment. * Advise patients to seek immediate medical attention if they develop any of these symptoms.
For full prescribing information, please visit www.BotoxMedical.com and www.BotoxCosmetic.com
Forward-Looking Statement
This press release contains “forward-looking statements,” including the statements by Dr. Whitcup and other statements regarding the safety, effectiveness, adverse events, approval and market potential 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; 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 2008 Form 10-K and Allergan’s Form 10-Q for the quarter ended March 31, 2009. 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 approximately 8,000 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.
© 2009 Allergan, Inc. Irvine, CA 92612. ® marks owned by Allergan, Inc.
1 Watkins CL, Leathley MJ, Gregson JM, Moore AP, Smith TL, Sharma AK. Prevalence of spasticity post stroke. Clin Rehabil. 2002; 16(5):515-22
2 National Stroke Association. New survey emphasizes need for more, better care after stroke. National Stroke Association Web site. http://www.stroke.org/site/DocServer/NSA_Stroke_Perceptions_Survey_Press_Release_final_pdf?docID=1943. Accessed February 20, 2009.
3 Allergan data on file; Medical Affairs
Contact:
Allergan Contacts Caroline Van Hove, 714-246-5134 (media) Crystal Muilenburg, 714-246-5842 (media) Jim Hindman, 714-246-4636 (investors) Joann Bradley, 714-246-4766 (investors) Emil Schultz, 714-246-4474 (investors)
