Allergan Announces Positive Top-Line Results from Phase III BOTOX(R) Headache Program
-- Phase III Studies Show Statistically Significant Decrease in Number of Headache Days --
Last update: 9:00 a.m. EDT Sept. 11, 2008
IRVINE, Calif., Sep 11, 2008 -- Allergan today announced that it has completed a top-line analysis of its two Phase III clinical trials exploring the use of BOTOX(R) (botulinum toxin type A) for the prophylactic treatment of headache in adults suffering from chronic migraine -- i.e., headaches and/or migraines that occur on 15 or more days each month.
BOTOX(R) is the first therapy being investigated for this extremely debilitating condition of chronic migraine, which is estimated to affect between 1.2 and 3.6 million people in the United States1a,b.
"We are pleased with the top-line results of our Phase III clinical trials which show that BOTOX(R) treatment provided benefit to these patients whose lives have been profoundly impacted by this severely debilitating condition," said Scott Whitcup, MD, Allergan's Executive Vice President, Research and Development. "It is gratifying to focus our research and development efforts on an indication that addresses such an important unmet medical need."
Based on this top-line analysis of its two Phase III clinical trials, Allergan hopes to file a supplemental biologics license application (sBLA) with the U.S. Food and Drug Administration (FDA) for the use of BOTOX(R) in chronic migraine by mid 2009. Full data results are expected to be published or presented by mid 2009.
Phase III Clinical Trials Design & Top-Line Findings
In the two Phase III clinical trials, patients were randomly assigned to treatment with BOTOX(R) or placebo injections every 12 weeks. The primary analysis was performed at week 24 following 2 treatment cycles. The two major efficacy measures evaluated in the trials were change from baseline in the number of headache episodes and number of headache days occurring in the 28 day-period preceding the week 24 time point. In Allergan's discussions with the FDA concerning the design of the Phase III clinical trials, the Agency considered number of headache days the preferred efficacy measure for the potential indication.
In the first Phase III clinical trial, Allergan prospectively selected number of headache episodes as the primary endpoint for evaluation. Number of headache days was selected as the major secondary endpoint. Results from the first Phase III clinical trial indicated that although both the BOTOX(R) and placebo treatment groups showed a statistically significant improvement from baseline, there was no significant difference in the reduction of number of headache episodes between patients receiving BOTOX(R) and placebo. However, the study showed a decrease in number of headache days, the FDA's preferred efficacy measure, that was significantly greater in patients receiving BOTOX(R) vs. patients receiving placebo (p=0.006). The decrease in number of migraine/probable migraine days was also found to be significantly greater in patients treated with BOTOX(R) vs. patients receiving placebo (p=0.002).
Based on the data from the first Phase III clinical trial, the primary endpoint for the second Phase III study was prospectively changed to number of headache days, with number of headache episodes changed to a secondary endpoint, before the data were unmasked. In the second Phase III study, the primary endpoint and key secondary endpoints showed statistically significant benefit of BOTOX(R) treatment over placebo injections. Specifically, patients treated with BOTOX(R) demonstrated a significantly greater decrease in both number of headache days (p<0.001) and number of headache episodes (p=0.003). Similar to the first Phase III trial, the second study also showed a decrease in number of migraine/probable migraine days that was significantly greater in patients treated with BOTOX(R) vs. placebo (p<0.001).
In both Phase III clinical trials, BOTOX(R) treatments were well tolerated in patients suffering from chronic migraine. Also, in both studies, quality of life was evaluated using the validated Headache Impact Test (HIT6). Importantly, patients receiving BOTOX(R) treatments scored statistically significantly higher improvement in quality of life vs. patients receiving placebo injections (p<0.001 in both studies).
About BOTOX(R)
BOTOX(R) is approved for the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia.
BOTOX(R) is approved 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(R) 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(R) is ineffective in chronic paralytic strabismus except when used in conjunction with surgical repair to reduce antagonist contracture.
And BOTOX(R) is approved for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents.
Who should not be treated with BOTOX(R)
BOTOX(R) injections should not be given to people who have an infection where the physician proposes to inject. They should not be given to people who are known to be sensitive to any ingredient in the BOTOX(R) product.
Warnings
Serious heart problems and serious allergic reactions have been reported rarely. If you think you're having an allergic reaction or other reaction, such as difficulty swallowing, speaking, or breathing, call your doctor immediately.
Patients with certain neuromuscular disorders such as ALS, myasthenia gravis, or Lambert-Eaton syndrome may be at increased risk of serious side effects.
Patients with neuromuscular disorders may be at increased risk of clinically significant systemic effects including severe dysphagia (difficulty swallowing) and respiratory compromise from typical doses of BOTOX(R).
Dysphagia (difficulty swallowing) is a commonly reported adverse event following treatment of cervical dystonia patients with all botulinum toxins. In these patients, there are reports of rare cases of dysphagia severe enough to warrant the insertion of a gastric feeding tube.
Precautions
Patients or caregivers should be advised to seek immediate medical attention if swallowing, speech, or respiratory disorders arise.
Side Effects
Localized pain, tenderness, and/or bruising may be associated with the injection.
In cervical dystonia, the most common side effects following injection include difficulty swallowing (19%), upper respiratory infection (12%), neck pain (11%), and headache (11%).
In blepharospasm, the most common side effects following injection include ptosis (20.8%), inflammation of the cornea (6.3%), and eye dryness (6.3%).
In strabismus, the most common side effects following injection include ptosis (15.7%) and vertical deviation (16.9%).
In severe primary axillary hyperhidrosis, the most common side effects (3-10% of patients) include injection-site pain and bleeding, non-underarm sweating, infection, sore throat, flu, headache, fever, neck or back pain, itching and anxiety.
Please see full product information at www.botox.com.
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.
Forward-Looking Statements
This press release contains "forward-looking statements," including the statements by Dr. Scott Whitcup and other statements regarding the safety, effectiveness, market potential and adverse events associated with BOTOX(R). 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 2007 Form 10-K and Allergan's Form 10-Q for the quarter ended June 30, 2008. Copies of Allergan's press releases and additional information about Allergan are 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.