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Allergan's BOTOX® Receives A Positive Opinion in Fourteen European Countries for Urinary Incontinence in Patients with MS or Spinal Cord Injury

BOTOX® injections can provide long-lasting bladder control for patients with neurogenic bladder

MARLOW, United Kingdom--(BUSINESS WIRE)-- Allergan is pleased to announce that BOTOX® (botulinum toxin type A) has received a positive opinion from the Irish Medicines Board for the management of urinary incontinence in adults with neurogenic detrusor overactivity (NDO) resulting from neurogenic bladder due to stable sub-cervical spinal cord injury, or multiple sclerosis.1 This is an important step towards securing national licences in the 14 European countries involved in the Mutual Recognition Procedure and marks a key milestone in bringing this innovative treatment to patients suffering from urinary incontinence due to neurogenic detrusor overactivity. The positive opinion is specific for BOTOX® and is based on Allergan's successful global phase III programme.

Between 60-80% of people with multiple sclerosis (MS)2,3 and 75-80% of people with spinal cord injury (SCI) will suffer from some degree of bladder dysfunction including urinary incontinence which can be distressing2-4. Urinary incontinence in patients with MS or SCI is frequently caused by a condition called neurogenic detrusor overactivity (NDO), 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 leaking). Targeted injections of BOTOX® into the bladder muscle have been shown to reduce the involuntary contractions and increase bladder capacity5,6. In turn, this reduces the number of urinary leaking episodes and may even stop leaking altogether in some patients1.

In Europe, approximately 656,000 people live with MS7 and, on average, nearly 11,000 people are diagnosed with SCI per year8,9. Many of these people face long-term mobility issues, yet remain professionally and socially active. Urinary incontinence can be a disabling and socially isolating condition10. It is also associated with significant quality of life and emotional well-being implications such as embarrassment, low self esteem, depression and loss of independence10. Other health implications of urinary incontinence in people living with MS or spinal cord injury include skin irritation and ulcers, kidney failure4,11 and recurrent urinary tract infections, which may lead to serious health consequences, if the overactivity of the detrusor muscle is not treated.

"We are pleased that BOTOX® has received a positive opinion following the Mutual Recognition Procedure 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 many people with spinal cord injury or multiple sclerosis, gaining effective control over their bladder and staying dry can be a significant step towards improving daily functioning and overall quality of life. Our task now is to work closely with the national health authorities to secure the relevant national licences so that we can bring this valuable treatment option to patients, as quickly as possible."

DIGNITY: The largest clinical trial programme in neurogenic detrusor overactivity

The DIGNITY programme (Double-blind InvestiGation of purified Neurotoxin complex In neurogenic deTrusor overactivitY) 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. 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, 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 8-10 months.

The results from the DIGNITY programme showed there was a significant reduction in frequency of urinary incontinence (leakage) reported in BOTOX® treated patients compared to placebo.1

  • Patients treated with 200 Units of BOTOX® experienced a highly statistically significant and clinically relevant reduction in the episodes of the most bothersome symptom, urinary incontinence (leakage), at week 6 compared to placebo. In fact, patients treated with 200 Units of BOTOX® experienced a reduction in the number of wetting episodes from 32.4 episodes/week at baseline to only 11.1 episodes / week by 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/week by week 6 (a reduction of only 10.5 episodes) (p<0.001)1
  • Nearly 40% of patients (37%) treated with 200 Units of BOTOX® were completely dry throughout week 6 compared to just 9% of patients treated with placebo1
  • Patients in the BOTOX® treatment groups experienced significant improvements in quality of life including less avoidance behaviour, less psychosocial impact and less embarrassment compared to those on the placebo treatment arm1

Like all medicines, BOTOX® 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, BOTOX® 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 urine1. Other side effects included difficulty in sleeping (insomnia), constipation, muscle weakness, muscle spasm, blood in the urine after the injection, painful urination after the injection, bulge in the bladder wall (bladder diverticulum), tiredness, 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 falls1.

Many patients with neurogenic bladder do not actively talk to their doctors or other healthcare professionals about their urinary leakage, hence may remain undiagnosed and under treated12. Current treatments are focussed primarily on oral anticholinergics as first line treatment and, if the condition cannot be managed with the anticholinergics, the last step for many patients is surgery. However, over 70% of patients with urinary incontinence stop taking oral anticholinergic treatments after just one year because of side effects or lack of efficacy and many are reluctant to have surgery, demonstrating the need for alternative minimally invasive treatments13.

In addition to the Mutual Recognition Procedure in Europe, Allergan is working with other health regulatory agencies around the world to bring this valuable minimally invasive treatment option to people living with multiple sclerosis or spinal cord injury who have urinary incontinence due to neurogenic detrusor overactivity.

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 bladder occurs 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. Botulinum toxin 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 overactivity14.

Countries involved in the Mutual Recognition Procedure (MRP)

For BOTOX®, Ireland serves as the Reference Member State in the Mutual Recognition Procedure. The other countries involved are Austria, Belgium, Denmark, Finland, Germany, Greece, Iceland, Italy, Luxemburg, Norway, Portugal, Spain, and Sweden.

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 from the bacterium, Clostridium botulinum.

In the UK, BOTOX® is licensed in adults for the treatment of15:

  • 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
  • treatment of post stroke spasticity in 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)

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

Allergan's botulinum toxin type A is licensed under the brand name of VISTABEL® for the treatment of glabellar lines (frown lines).

About Allergan, Inc.

Allergan 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 approximately 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, medical devices and over-the-counter consumer products, 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 eye care, neurosciences, medical aesthetics, medical dermatology, breast aesthetics, obesity intervention and urologics, Allergan is proud to celebrate 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. Ingram and other statements regarding research and development outcomes, efficacy, adverse reactions, market and product potential, product availability and other statements regarding neurogenic bladder and BOTOX®. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialise, 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 2010 Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q.

© Allergan Ltd. BOTOX® and VISTABEL® are registered trademarks owned by Allergan, Inc.

References

1. Mutual Recognition Procedure BOTOX® Summary of Product Characteristics

2. Kalsi V et al. Therapy Insight: bladder dysfunction associated with multiple sclerosis. Nat Clin Pract Urol. 2005;2(10):492-501.

3. Giannontoni A et al. Urological dysfunctions and upper urinary tract involvement in multiple sclerosis patients. Neurourol Urodynamics. 1998;17:89-98

4. 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

5. 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), doi:10.1016/ j.eururo.2011.07.002

6. 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

7. Multiple Sclerosis International Federation. Atlas of MS Database. http://www.atlasofms.org/index.aspx. Accessed Dec 2010

8. International Campaign for Cures of Spinal Cord Injury Paralysis. Web site: http://www.campaignforcure.org/iccp/index.php?option=com_content&task=view&id=13&Itemid=28

9. Eurostat Population of EU http://epp.eurostat.ec.europa.eu/tgm/table.do?tab=table&language=en&pcode=tps00001&tableSelection=1&footnotes=yes&labeling=labels&plugin=1. Accessed August 2011

10. Tubaro A. Defining overactive bladder: epidemiology and burden of disease. Urology. 2004;64(6 Suppl 1):2-6.

11. Calabresi P et al. Impaired renal function in progressive multiple sclerosis. Neurology 2002;59;1799

12. Mahajan S et al. Under treatment of overactive bladder symptoms in patients with multiple sclerosis: An ancillary analysis of the NARCOMS patient registry. J Urol. 2010;183:1432-1437

13. Manack A et al. Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database. Neurourol Urodyn. 2010;30(3):395-401

14. Pannack J et al. Guidelines on neurogenic lower urinary tract dysfunction. European Association of Urology. 2011 www.uroweb.org/gls/pdf/17_Neurogenic%20LUTS.pdf Accessed August 2011

15. BOTOX® Summary of Product Characteristics www.medicines.org.uk/emc/

Media contacts
Allergan
Janet Kettels, kettels_janet@allergan.com or +44 7738 506 476
or
CCA London
Kate Perry, k.perry@cca-uk.com or +44 207 632 1896

Source: Allergan, Inc.

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