Posted Wednesday, August 24, 2011
News from Allergan: BOTOX® (onabotulinumtoxinA) Receives U.S. FDA Approval for the Treatment of Urinary Incontinence in Adults with Neurological Conditions Including Multiple Sclerosis and Spinal Cord Injury - Clinical Trials Showed Approximately 20 Fewer Urinary Leaking Episodes Per Week At Week Six; BOTOX® Proven Effective Up To 10 Months In Patients Who Have An Inadequate Response To Or Are Intolerant
IRVINE, Calif.--(BUSINESS WIRE)-- Allergan, Inc. (NYSE:AGN) today announced the United States Food and Drug Administration (FDA) has approved BOTOX® (onabotulinumtoxinA) for injection for the treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (e.g. spinal cord injury (SCI), multiple sclerosis (MS)) in adults who have an inadequate response to or are intolerant of an anticholinergic medication.1 Urinary incontinence (bladder leakage) due to detrusor (bladder muscle) overactivity in patients living with MS or SCI is a chronic condition affecting approximately 340,000 people in the United States.2 Current standard of care includes oral medications that are taken regularly, known as anticholinergics; however, it is estimated that 71 percent of people stop taking at least one oral medication within 12 months.3 If oral medications fail, then surgery may be considered (e.g. implanting a neuromodulation device or bladder augmentation surgery). BOTOX® neurotoxin was studied in people living with MS and SCI with urinary incontinence due to detrusor overactivity who had an inadequate response to or who were intolerant of an anticholinergic medication. In Allergan's two Phase III clinical trials, injecting 200 units of BOTOX® directly into the bladder muscle reduced urinary incontinence episodes by approximately 20 episodes per week at week six (19.9 and 19.6 episodes/week vs. 10.6 and 10.8 for the placebo group)).4 Patients in the clinical trials were considered for retreatment with BOTOX® when the clinical effect of their previous treatment wore off, which in the trials was up to 10 months (42-48 weeks for the 200U BOTOX® group vs. 13-18 weeks for the placebo group). "Urinary incontinence due to detrusor overactivity in patients with a neurologic condition is a serious medical problem, and for people who do not respond to or cannot tolerate the side effects of an oral anticholinergic medication, BOTOX® is a new long-lasting treatment option to reduce urinary incontinence episodes and address a particularly burdensome issue," said Scott Whitcup, M.D., Allergan's Executive Vice President, Research and Development and Chief Scientific Officer. "We are proud to bring the seventh medical use of BOTOX® in the United States to market. BOTOX® is the first neurotoxin to undergo formal clinical evaluation and receive FDA approval for a urological indication. This approval of BOTOX® is an important milestone in Allergan's commitment to develop and make available novel treatment options for urologists and their patients." People living with MS develop lesions on the spinal cord, while people who sustain a spinal cord injury have irreversible nerve damage, resulting in the inability of the spinal cord and bladder to communicate effectively. As a result, the bladder muscle involuntarily contracts, increasing the pressure in the bladder and decreasing the volume of urine the bladder can hold, which causes the individual to leak urine frequently and unexpectedly.5,6 BOTOX® neurotoxin temporarily prevents muscle contractions by blocking the transmission of nerve impulses to the muscle, in this case, the bladder muscle, by selectively preventing the release of the neurotransmitter acetylcholine (ACh) at the neuromuscular junction.7 "Urinary incontinence or leakage is often considered a taboo subject. Studies have shown that many patients are undiagnosed and undertreated because they are too embarrassed to talk to their doctor about their symptoms. This is particularly true for patients with neurological conditions that are associated with urinary incontinence due to detrusor overactivity. Many of these patients don't get referred to a urologist who can diagnose and manage their bladder condition,"8 said Dr. Victor Nitti*, Vice-Chairman, Department of Urology, NYU Langone Medical Center, who was involved in the BOTOX® Phase III clinical trial program. "When not adequately managed, urinary incontinence due to detrusor overactivity in patients living with MS or SCI can lead to skin irritation, ulcers, pressure increases in the bladder that can cause kidney failure, as well as recurrent urinary tract infections."
The BOTOX® Phase III Clinical Trial Program in MS and SCI Patients with Urinary Incontinence Due to Detrusor Overactivity
Allergan's Phase III clinical trial program evaluated the safety and efficacy of BOTOX® injections as a treatment for adults with urinary incontinence due to detrusor overactivity associated with a neurologic condition such as MS or SCI. The program consisted of two pivotal Phase III trials, involving 691 patients (n=381 Multiple Sclerosis, 310 Spinal Cord Injury; T1 injury or below), who had an inadequate response to or were intolerant of an anticholinergic medication. Eligible patients needed to either be performing or willing and able to learn how to perform clean intermittent catheterization (CIC), a method used to empty their bladder. Patients were randomized to receive a physician-administered treatment of 200U BOTOX® neurotoxin or placebo injected across the bladder muscle using a rigid or flexible cystoscope, a specialized tube with an optical lens at the end that is used to see inside the bladder. A cystoscope is placed into the bladder via the urethra under local anesthesia if requested by the patient.5,11 Results from the two Phase III clinical trials showed significant reductions in the frequency of urinary incontinence episodes in patients treated with 200U of BOTOX® neurotoxin compared to placebo within two weeks (15.3 and 18 episodes/week vs. 10 and 7.9, respectively) and approximately 20 fewer urinary incontinence episodes at week six versus placebo (19.9 and 19.6 episodes/week vs. 10.6 and 10.8, respectively). The results were similar between placebo- and BOTOX® treated patients in the Phase III clinical trials in patients that received 200U of BOTOX® neurotoxin irrespective of concomitant anticholinergic use. BOTOX® is approved as a 200U dose for patients with urinary incontinence due to detrusor overactivity associated with a neurologic condition. Patients should be considered for retreatment with BOTOX® when the clinical effect of the previous treatment wears off. In the Phase III clinical trials, this was up to 10 months (42-48 weeks for the 200U BOTOX® group vs. 13-18 weeks for the placebo group). The most frequently reported adverse reactions within 12 weeks of receiving BOTOX® injections for detrusor overactivity associated with a neurologic condition include urinary tract infection (24%), urinary retention (17%), hematuria (4%), fatigue (4%), and insomnia (2%). The following adverse event rates were reported following initial injection (median duration of 44 weeks of exposure): urinary tract infections (49%), urinary retention (17%), fatigue (6%), constipation (4%), muscular weakness (4%), dysuria (4%), fall (3%), gait disturbance (3%), insomnia (3%), and muscle spasm (2%).
About BOTOX® (onabotulinumtoxinA)
BOTOX® is a prescription-only medical product that contains tiny amounts of highly purified botulinum toxin protein refined from the bacterium, Clostridium botulinum. BOTOX® has a unique, protected molecular structure that stabilizes the core toxin in BOTOX® from degradation. When injected at FDA-approved and labeled doses into a specific muscle or gland, BOTOX® neurotoxin is expected to diffuse locally and produce a safe and effective result by producing a localized and temporary reduction in the overacting muscle or gland, usually lasting up to approximately three months depending on the individual patient. BOTOX® was first approved by the FDA 21 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® neurotoxin is also approved to treat the abnormal head position and neck pain that happens with cervical dystonia (CD) in adults, symptoms of severe underarm sweating (severe primary axillary hyperhidrosis) when medicines used on the skin (topical) do not work well enough, as well as for the treatment of increased muscle stiffness in elbow, wrist, and finger muscles in adult patients with upper limb spasticity. Most recently, in 2010, BOTOX® was approved by the FDA for the prophylactic treatment of headaches in adults with Chronic Migraine, a distinct and severe neurological disorder characterized by patients who have a history of migraine and suffer from headaches on 15 or more days per month with headaches lasting four hours a day or longer. In addition to its therapeutic uses, the same formulation of BOTOX® with dosing specific to moderate to severe glabellar lines was approved by the FDA in 2002 under the trade name BOTOX® Cosmetic (onabotulinumtoxinA). BOTOX® Cosmetic is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines (frown lines between the eyebrows) associated with corrugator and/or procerus muscle activity in adult patients up to 65 years of age. In addition to 21 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 trials.9 Worldwide, approximately 26 million vials of BOTOX® and BOTOX® Cosmetic have been distributed and approximately 29 million treatment sessions have been performed over the past 20 years (1989-2009).10 With approximately 2,300 articles on BOTOX® and BOTOX® Cosmetic in scientific and medical journals,11 BOTOX® neurotoxin is one of the most widely researched medicines in the world.