Allergan's BOTOX® (Botulinum Toxin Type A) Receives UK Authorisation for Urinary Leakage in Patients With Multiple Sclerosis or Spinal Cord Injury

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Allergan

27 Sep, 2012, 07:30 GMT

MARLOW, England, September 27, 2012 /PRNewswire/ --

Allergan, Inc. is pleased to announce that BOTOX® has been licensed by the Medicines and Healthcare Products Regulatory Agency (MHRA) for the management of urinary incontinence in adult patients with neurogenic detrusor overactivity (NDO) due to subcervical spinal cord injury (SCI) (traumatic or non-traumatic) or multiple sclerosis (MS), who are not adequately managed with anticholinergics[1],[2]. The marketing authorisation is specific for Allergan's botulinum toxin type A product and is a key milestone in bringing this innovative treatment to people living with MS or SCI who have urinary leakage, providing them with a long-term solution for bladder control. Indeed, recently published NICE Guidelines recommend the use of botulinum toxin type A to treat patients with MS or SCI who have symptoms of an overactive bladder and in whom oral treatments have been ineffective or poorly tolerated[3].

Approximately 140,000 people in the UK are living with MS or SCI[4],[5]. Between 75-80% of people with MS and 60-80% of people with SCI will suffer from some degree of bladder dysfunction including urinary leakage which can be extremely distressing[6]-[8]. Urinary leakage in patients with MS or SCI is frequently caused by a condition called neurogenic detrusor overactivity, which results in involuntary contractions of the bladder during the filling stage when the bladder should be relaxed. This overactivity can lead to urinary incontinence (uncontrolled urinary leakage). Current treatment options include oral medications that need to be taken daily. However, less than 30% of patients manage to stay on oral medication for longer than a period of 12 months[9]. If oral medications fail to control the leakage, then patients may require surgical intervention. Targeted injections with Allergan's botulinum toxin type A product into the bladder muscle have been shown to reduce the involuntary contractions and increase bladder capacity[10],[11]. In turn, this reduces the number of urinary leakage episodes and may even stop leakage altogether in some patients[1].

"Historically, the management of urinary incontinence due to NDO has relied on daily medications. However, many patients find that daily medications are difficult to adhere to and sometimes these medications have limited effect," said Professor Christopher Chapple, Urology Department, Royal Hallamshire Hospital, Sheffield NHS Trust and a key investigator in the neurogenic detrusor overactivity registration trials. "Now, BOTOX® injections, given every 8-10 months into the bladder means that I have a new and potentially life changing treatment solution to help my patients get this distressing condition under control. Being able to better control and manage bladder function can be life-changing for patients."

Many people living with MS and SCI face long-term mobility issues, yet remain professionally and socially active. Urinary leakage can be a disabling and socially isolating condition[12]. The condition is associated with significant quality of life and emotional well-being implications such as embarrassment, low self-esteem, depression and loss of independence[3],[12]. Other health implications of urinary incontinence include skin irritation and ulcers, kidney failure[8],[13]and recurrent urinary tract infections[3], which may lead to serious health consequences if the overactivity of the detrusor muscle is not treated.

Many people who have neurological diseases and are suffering from urinary incontinence remain undiagnosed and untreated. Amy Bowen, Director of Service Development at the MS Trust, explained, "For many people with MS, urinary leakage is frequently seen as a taboo subject with patients often reluctant or too embarrassed to talk about the symptoms to anyone. As a result, many people with MS can feel distressed, socially isolated and that they lack of control over their condition. It is a really positive development that there is now an additional, effective treatment option to help manage this difficult problem. Hopefully, more people with MS who are struggling with urinary leakage will feel confident to discuss these symptoms with their MS specialists and find the treatment option that is right for them."

Alex Rankin, Director of Services for ASPIRE also welcomed the announcement "Many people who have been paralysed by spinal cord injury have to learn new techniques to manage their bladder. BOTOX® injections could now help a person with Spinal Cord Injury have better control over when and where they empty their bladder. This independence will lead to a greatly improved quality of life."

DIGNITY: The largest clinical trial programme in neurogenic detrusor overactivity

The DIGNITY programme was Allergan's phase III clinical programme evaluating the safety and efficacy of BOTOX® as a treatment in patients suffering from urinary incontinence due to neurogenic detrusor overactivity[1]. The programme consisted of two pivotal trials involving nearly 700 patients with either spinal cord injury or multiple sclerosis who were not adequately managed with at least one anticholinergic therapy. Eligible patients needed to be willing to perform clean intermittent catheterisation (CIC) to remove urine from the body, if required.

Patients were randomised to receive a physician-administered single treatment of placebo, or 200 or 300 Units of BOTOX® injected as one procedure into the detrusor muscle using a rigid or flexible cystoscope. Treatment was shown to be effective within 2 weeks and lasted for approximately 42 weeks (or 9 months)[1].

The results from the DIGNITY programme showed there was a highly statistically significant and clinically relevant reduction in frequency of the most bothersome symptom, urinary incontinence (leakage), reported in BOTOX® treated patients compared to placebo[1].

  • 76% of patients treated with Allergan's botulinum toxin type A product had a statistically significant reduction in urinary wetting episodes (defined as ≥ 50% reduction) by week 6[1]
  • Patients treated with 200 Units of Allergan's botulinum toxin type A product experienced a statistically significant reduction in the number of wetting episodes from 32.4 episodes/week at baseline to only 12.4 episodes during week 6 (a reduction of 21.3 episodes). In contrast, patients treated with placebo had an average of 31.5 episodes/week at baseline which was reduced to 21.0 episodes during week 6 (a reduction of only 10.5 episodes) (p<0.001)[1]
  • Nearly 40% of patients treated with 200 Units of Allergan's botulinum toxin type A product were completely dry during week 6 compared to just 9% of patients treated with placebo[1]
  • Patients treated with Allergan's botulinum toxin type A product experienced statistically significant improvements in quality of life including less avoidance behaviour, less psychosocial impact and less embarrassment compared to those on the placebo treatment arm[1]

"Allergan is pleased that BOTOX® has received the marketing authorisation in the UK for the treatment of urinary incontinence in people living with multiple sclerosis or spinal cord injury," said Douglas Ingram, President of Allergan in Europe, Africa and the Middle East. "For people with spinal cord injury or multiple sclerosis, gaining effective control over their bladder and staying dry can be a significant step towards improving overall quality of life."

Like all medicines, Allergan's botulinum toxin type A product can cause side effects, although not everybody gets them. In general, side effects occur within the first few days following injection. They usually last only for a short time, but they may last for several months and in rare cases, longer. Overall, Allergan's botulinum toxin type A product treatment was generally well-tolerated in the majority of patients in the phase III clinical trial programme. The most common adverse reactions were mainly associated with the urinary tract and included urinary tract infections and the inability to empty the bladder (urinary retention) in patients who were not using a catheter to remove urine[1]. Other side effects included difficulty in sleeping (insomnia), tiredness, constipation, muscle weakness or spasm, blood in the urine after the injection, bulge in the bladder wall (bladder diverticulum), problems with walking (gait disturbance), possible uncontrolled reflex reaction of the body (e.g. profuse sweating, throbbing headache or increase in pulse rate) around the time of the injection (autonomic dysreflexia) or falls[1].

Notes to Editors

About Detrusor (Bladder) Overactivity

The detrusor muscle is the most important muscle of the bladder and contracts when urinating to squeeze out urine. Otherwise, it remains relaxed to allow the bladder to fill. Other muscles involved in urination include the urethral sphincter muscles which control the flow of urine. Detrusor overactivity is characterised by involuntary bladder contractions which can lead to urinary incontinence (wetting or leaking) as well as urgency to urinate or an increased need to urinate. It is commonly divided into two categories: idiopathic detrusor overactivity (IDO) where the cause is unknown and neurogenic detrusor overactivity (NDO) resulting from neurogenic bladder. Neurogenic bladderoccurs when the nerves controlling the detrusor muscle, predominantly in the spinal cord, are damaged - for example by lesions in the spine (such as plaques caused by MS) or an injury to the spinal cord (SCI). Given the nature of their underlying conditions, the nerve damage for most patients with neurogenic bladder cannot be repaired. Reducing the number of involuntary detrusor muscle contractions with BOTOX® is one way to treat bladder issues in patients with NDO. As well as the NICE recommendation[3], botulinum toxin type A is currently recommended in the 2011 European Association of Urology guidelines, with a grade A recommendation as an effective, minimally invasive treatment to reduce neurogenic detrusor overactivity[14].  

About BOTOX®

BOTOX® (botulinum toxin type A) from Allergan is a prescription-only medicine that contains tiny amounts of highly purified botulinum toxin protein refined refined from the bacterium, Clostridium botulinum.

In the UK, BOTOX® is licensed in adults for the treatment of[1]:

  • blepharospasm (uncontrolled blinking of the eyelids)
  • hemifacial spasm (a neuromuscular disorder characterised by unpredictable and involuntary twitching of facial muscles on one side of the face)
  • cervical dystonia (a muscle condition affecting the neck making it difficult to hold the head up straight)
  • severe axillary hyperhidrosis (excessive sweating of the armpits) which does not respond to topical treatment with antiperspirants or antihidrotics
  • treatment of post stroke spasticity of the hand and wrist
  • prophylaxis of headaches in adults who have chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine)
  • temporary improvement in the appearance of moderate to severe vertical lines between the eyebrows seen at frown (glabellar lines), in adults <65 years old
  • leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis, not adequately controlled with anticholinergic medicines

In addition, BOTOX® is also indicated to treat dynamic equinus foot deformity in children aged two years and older who have cerebral palsy.

About Allergan

Allergan, Inc. is a multi-specialty health care company established more than 60 years ago with a commitment to uncover the best of science and develop and deliver innovative and meaningful treatments to help people reach their life's potential. Today, we have more than 10,000 highly dedicated and talented employees, global marketing and sales capabilities with a presence in more than 100 countries, a rich and ever-evolving portfolio of pharmaceuticals, biologics, over-the-counter medicines and medical devices, and state-of-the-art resources in R&D, manufacturing and safety surveillance that help millions of patients see more clearly, move more freely and express themselves more fully. From our beginnings as an eye care company to our focus today on several medical specialties, including ophthalmology, neurosciences, obesity, urologics, medical aesthetics and dermatology, Allergan is proud to celebrate more than 60 years of medical advances and proud to support the patients and physicians who rely on our products and the employees and communities in which we live and work.

Forward-Looking Statement

This press release contains "forward-looking statements", including but not limited to the statements by Mr Douglas Ingram, Professor Christopher Chapple, Ms Amy Bowen, Mr Alex Rankin and other statements regarding the DIGNITY programme, the NICE recommendation, likelihood of marketing authorisation for BOTOX®, research and development outcomes, efficacy, adverse reactions, market and product potential, product availability and other statements regarding BOTOX® and Allergan. 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 and pharmaceutical market conditions; technological advances and patents attained by competitors; challenges inherent in the research and development and regulatory processes; challenges related to new product marketing, such as the unpredictability of market acceptance for new pharmaceutical products and/or the acceptance of new indications for such products; inconsistency of treatment results among patients; potential difficulties in manufacturing a new product; 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 U.S. Securities and Exchange Commission, including the discussion under the heading "Risk Factors" in Allergan's 2011 Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q.

® Marks owned by Allergan, Inc.

References

  1. BOTOX® Summary of Product Characteristics (http://www.medicines.org.uk)
  2. BOTOX® Patient Information Leaflet (http://www.medicines.org.uk)
  3. Urinary Incontinence in neurological disease: management of lower urinary tract dysfunction in neurological disease. Commissioned by the National Institute for Health and Clinical Excellence. (http://www.nice.org.uk/nicemedia/live/13855/60375/60375.pdf; accessed August 2012)
  4. Thomas SL, et al. Estimating the prevalence of multiple sclerosis in the United Kingdom. MS Society 2009:1-3
  5. Nichols K, Brown A, Sett P. Spinal cord injury - the condition and it's acute management. Hosp Pharm. 2005; 12: 91-4
  6. Kalsi V, et al. Therapy Insight: bladder dysfunction associated with multiple sclerosis.Nat Clin Pract Urol. 2005;2(10):492-501
  7. Giannantoni A, et al. Urological dysfunctions and upper urinary tract involvement in multiple sclerosis patients. Neurourol Urodynamics. 1998;17:89-98
  8. Erol B, et al. The relationship between level of injury and bladder behavior in patients with post-traumatic spinal cord injury. Ulus Travma Acil Cerrahi Derg. 2009;15:377-382
  9. Manack A, et al. Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database. Neurourol Urodyn. 2010;30(3):395-401
  10. Cruz F, et al. Efficacy and Safety of OnabotulinumtoxinA in Patients with Urinary Incontinence Due to Neurogenic Detrusor Overactivity: A Randomised, Double-Blind, Placebo-Controlled Trial. Eur Urol. 2011;60:742-50
  11. Karsenty G, et al. Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol. 2008;53(2):275-87
  12. Tubaro A. Defining overactive bladder: epidemiology and burden of disease. Urology. 2004;64(6 Suppl 1):2-6.
  13. Calabresi P, et al. Impaired renal function in progressive multiple sclerosis. Neurology 2002;59;1799
  14. Pannek J, et al. Guidelines on neurogenic lower urinary tract dysfunction. European Association of Urology. 2011 (http://www.uroweb.org/gls/pdf/17_Neurogenic%20LUTS.pdf; accessed August 2012)