Allergan, Inc. has received the US Food and Drug Administration (FDA) approval for 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 anti-cholinergic medication.
In two double-blind, randomized, multi-centre, 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 three 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).
"Allergan has a long-standing commitment to study the potential of Botox to treat a number of different medical conditions," said Scott Whitcup, MD, executive vice president, Research and Development, chief scientific officer of Allergan. "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). 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. It is estimated, however, that greater than 50 per cent 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.
"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 Centre. "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 re-treatment. To qualify for re-treatment, 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.
The US FDA approval of Botox was based on safety and efficacy data from two double-blind, randomized, multi-centre, 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 anaesthetic, 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 per cent 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). 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). 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.
Botox is a prescription-only medical product that contains tiny amounts of a highly purified botulinum toxin protein refined from the bacterium, Clostridium botulinum. The Botox formula contains auxiliary proteins that stabilize the core toxin in Botox from degradation. When injected at doses approved by the FDA into a specific muscle or gland, Botox neurotoxin is expected to act locally to produce a safe and effective result, usually lasting between three to ten months depending on the approved indication and on the individual patient.
BOTOX was first approved by the FDA more than 22 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. Today, BOTOX neurotoxin is approved to treat a total of eight medical conditions in the United States, including 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; for the treatment of increased muscle stiffness in elbow, wrist, and finger muscles in adult patients with upper limb spasticity; 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; 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; and 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 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 corrugators and/or procerus muscle activity in adult patients up to 65 years of age.
Since its first approval in 1989, Botox has been recognised by regulatory authorities worldwide as an effective treatment for 26 different indications in approximately 85 countries, benefiting millions of patients worldwide.
Allergan is a multi-specialty health care company and committed to uncover the best of science and develop and deliver innovative and meaningful treatments to help people reach their life's potential.