BOTOX Wins FDA Approval for Treatment of Overactive Bladder for Adults

Allergan, Inc. AGN announced today that the U.S. Food and Drug Administration (FDA) has approved BOTOX^® (onabotulinumtoxinA) for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency and frequency in adults who have had an inadequate response to or are intolerant of an anticholinergic medication. In two double-blind, randomized, multi-center, placebo-controlled 24-week clinical trials among adults with overactive bladder who had not been adequately managed with anticholinergic treatments, BOTOX^® reduced daily urinary incontinence (leakage) episodes as compared to placebo by 50 percent or more by week 12 (reduction of 2.5 episodes from baseline of 5.5 episodes in one study and reduction of 3 episodes from baseline of 5.5 episodes in the second study for those treated with BOTOX® vs. a reduction of 0.9 episodes from a baseline of 5.1 episodes in one study and a reduction of 1.1 episodes from a baseline of 5.7 episodes in the second study for those treated with placebo).^1 “Allergan has a long-standing commitment to study the potential of BOTOX® to treat a number of different medical conditions,” said Scott Whitcup, M.D., Allergan's Executive Vice President, Research and Development, Chief Scientific Officer. “With today's approval, BOTOX® is now approved for 26 different indications in more than 85 countries. Most importantly, today's FDA approval is a milestone in the treatment of this burdensome condition and will provide a novel option for urologists and their OAB patients.” While the exact cause is often unknown, OAB is a medical condition that results in an uncontrolled urge to urinate, frequent urination and, in many patients, uncontrollable leakage of urine. In the United States, an estimated 14.7 million adults experience symptoms of OAB with urinary incontinence (unexpected leakage of urine).^2 Anticholinergics, which are often prescribed as pills, are used by approximately 3.3 million Americans with OAB, with or without urinary incontinence, to manage their condition.^3 It is estimated, however, that greater than 50 percent of these patients stop taking at least one oral medication within 12 months, likely due to an inadequate response to, or intolerance of, the medication.^4 “Overactive bladder can be a difficult condition to treat as there have been limited options for patients when currently available medications have failed to provide them with adequate relief,” said Dr. Victor Nitti*, Vice Chairman, Department of Urology and Director of Female Pelvic Medicine and Reconstructive Surgery at NYU Langone Medical Center. “With the approval of BOTOX®, we have a new treatment option to offer these patients that has demonstrated efficacy in reducing urinary leakage and other symptoms of OAB with the effect lasting up to six months.” The median duration for efficacy with BOTOX® at reducing urinary leakage and other symptoms of OAB in the two clinical studies was 135-168 days compared to 88-92 days with placebo based on qualification for retreatment. To qualify for retreatment, at least 12 weeks must have passed since the prior treatment, post-void residual urine volume must have been less than 200 mL and patients must have reported at least two urinary incontinence episodes over three days. BOTOX® treatment relieves OAB symptoms by temporarily calming muscle contractions by blocking the transmission of nerve impulses to the bladder muscle. OAB Clinical Development Program The FDA approval of BOTOX® was based on safety and efficacy data from two double-blind, randomized, multi-center, placebo-controlled 24-week clinical studies of 1,105 adult patients whose OAB symptoms had not been adequately managed with anticholinergic therapy, either due to lack of efficacy or intolerance of the medication. To qualify for the study, patients had to have symptoms of OAB with symptoms of urge urinary incontinence, urgency and frequency, and experience a minimum of three urinary urgency leakage (incontinence) episodes and at least 24 urination episodes (micturitions) over a three-day timeframe. Patients in the studies were randomized to receive physician-administered treatment with 100 units of BOTOX® neurotoxin (n=557) or placebo (n=548) injected directly into the detrusor (bladder) muscle. Patients were treated in the physician's office and received a local anesthetic, with or without sedation, to numb the bladder prior to treatment with BOTOX® or placebo. In both clinical trials, patients treated with BOTOX® experienced a reduction of 50% or more in the frequency of daily urinary incontinence episodes from baseline compared to placebo at week 12 (reduction of 2.5 episodes from baseline of 5.5 episodes in one study and reduction of 3 episodes from baseline of 5.5 episodes in the second study for those treated with BOTOX® vs. a reduction of 0.9 episodes from a baseline of 5.1 episodes in one study and a reduction of 1.1 episodes from a baseline of 5.7 episodes in the second study for those treated with placebo).^1 In addition, approximately three times as many patients treated with BOTOX® in the clinical studies achieved a complete elimination of their leakage episodes as compared to placebo (22.9% and 31.4% achieved complete continence with BOTOX® vs. 6.5% and 10.3% with placebo at week 12 in the two clinical trials).^5 Improvements in other symptoms of overactive bladder, including urge to urinate, frequency of urination and the amount of urine voided also occurred with BOTOX® treatment compared to placebo at week 12. In the clinical studies, the most frequently reported adverse reactions within 12 weeks of receiving BOTOX® injections included urinary tract infection (18% vs. 6% with placebo), dysuria (9% vs. 7% with placebo), which means painful or difficult urination; and urinary retention (6.5% vs. 0.4% with placebo), which is a temporary inability to fully empty the bladder requiring the use of a disposable self-catheter.