1. OnabotulinumtoxinA for Urinary Incontinence from Neurogenic Detrusor Overactivity

2. Study Design 416 patients (227 MS; 189 spinal cord injury) with neurogenic detrusor overactivity and urinary incontinence (UI) Randomized 1:1:1 to placebo, 200 U onabotulinumtoxinA, or 300 U onabotulinumtoxinA Primary endpoints (assessed at 6 weeks) –Change from baseline in the number of weekly episodes of UI –Decrease in weekly UI episodes from baseline, categorized as ≥50%, ≥75%, and 100%, or dry Secondary endpoints (assessed at 6 weeks) –Maximum cystometric capacity –Maximum detrusor pressure during the first involuntary detrusor pressure –Incontinence quality of life total summary score 416 patients (227 MS; 189 spinal cord injury) with neurogenic detrusor overactivity and urinary incontinence (UI) Randomized 1:1:1 to placebo, 200 U onabotulinumtoxinA, or 300 U onabotulinumtoxinA Primary endpoints (assessed at 6 weeks) –Change from baseline in the number of weekly episodes of UI –Decrease in weekly UI episodes from baseline, categorized as ≥50%, ≥75%, and 100%, or dry Secondary endpoints (assessed at 6 weeks) –Maximum cystometric capacity –Maximum detrusor pressure during the first involuntary detrusor pressure –Incontinence quality of life total summary score Ginsberg D, et al. J Urol. 2012;187:2131-2139.

3. Urinary Incontinence Change from Baseline at Week 6* *MS and spinal cord injury patients combined; similar results seen in both subpopulations. † P <.001 vs placebo. Abbreviation: UI, urinary incontinence. Ginsberg D, et al. J Urol. 2012;187:2131-2139. Change from baseline in UI episodes Patients attaining ≥50% reduction in weekly UI Patients achieving dry status -30% 38% 10% OnabotulinumtoxinA 200 U (n = 135) Placebo (n = 149) OnabotulinumtoxinA 300 U (n = 132) -67% 75% † 36% † -74% 77% † 41% †

4. Urologic and Quality of Life Parameters Change from Baseline at Week 6* *MS and SCI patients combined; similar results seen in both subpopulations. † P <.05 vs placebo. ‡ Higher scores indicate improvement. Abbreviation: IDC, involuntary detrusor contraction. Ginsberg D, et al. J Urol. 2012;187:2131-2139. Urinary incontinence (no. per wk.) Maximum cystometric capacity (mL) Maximum detrusor pressure at first IDC (H 2 O) Incontinence quality of life total summary score ‡ -8.8 16 -2.4 10.8 OnabotulinumtoxinA 200 U (n = 135) Placebo (n = 149) OnabotulinumtoxinA 300 U (n = 132) -21.0 † 151 † -35.1 † 26.9 † -22.7 † 168 † -33.3 † 32.9 †

5. Urologic and Quality of Life Parameters in MS Patients Change from Baseline at Week 6 *P <.05 vs placebo. † Higher scores indicate improvement. Abbreviation: IDC, involuntary detrusor contraction. Ginsberg D, et al. J Urol. 2012;187:2131-2139. Urinary incontinence (no. per wk.) Maximum cystometric capacity (mL) Maximum detrusor pressure at first IDC (cm H 2 O) Incontinence quality of life total summary score † -11.5 -7.5 12.1 12.4 OnabotulinumtoxinA 200 U (n = 77) Placebo (n = 81) OnabotulinumtoxinA 300 U (n = 69) -20.4 142* -28.4* 28.0* -23.8* 162* -29.0* 38.3*

6. Patients with Urinary Retention and Urinary Tract Infections Abbreviations: MS, multiple sclerosis; SCI, spinal cord injury. Ginsberg D, et al. J Urol. 2012;187:2131-2139. Urinary retention MS patients SCI patients Urinary tract infection MS patients SCI patients 4 (5%) 1 (2%) 22 (28%) 27 (42%) OnabotulinumtoxinA 200 U Placebo OnabotulinumtoxinA 300 U 22 (29%) 5 (9%) 38 (50%) 28 (48%) 19 (28%) 4 (5%) 34 (51%) 30 (50%)

7. *MS and spinal cord injury patients combined. † P =.004. Ginsberg D, et al. J Urol. 2012;187:2131-2139. Mean change (mL) % patients with postvoid residual ≥200 mL 7 ± 55 4 OnabotulinumtoxinA 200 U (n = 60) Placebo (n = 58) OnabotulinumtoxinA 300 U (n = 55) 106 ± 165 † 32 169 ± 300 † 36 Postvoid Residual at Week 2*

8. Patients Initiating Intermittent Catheterization During Treatment Cycle 1* *Patients with no intermittent catheterization at baseline; MS and spinal cord injury patients combined. Ginsberg D, et al. J Urol. 2012;187:2131-2139. Any reason Urinary retention 13 (22%) 6 (10%) OnabotulinumtoxinA 200 U (n = 60) Placebo (n = 58) OnabotulinumtoxinA 300 U (n = 55) 28 (47%) 21 (35%) 27 (49%) 23 (42%)

9. Take-Home Messages Neurogenic detrusor overactivity (NDO) and related incontinence symptoms seriously impact the quality of life of many MS patients, but may not always be recognized by clinicians; therefore, all patients should be screened for these issues Anticholinergics are the initial treatment for NDO-related urinary incontinence, but if they fail, other very effective options are available, including onabotulinumtoxinA Depending on the individual, treatment with onabotulinumtoxinA may require intermittent self-catheterization Neurogenic detrusor overactivity (NDO) and related incontinence symptoms seriously impact the quality of life of many MS patients, but may not always be recognized by clinicians; therefore, all patients should be screened for these issues Anticholinergics are the initial treatment for NDO-related urinary incontinence, but if they fail, other very effective options are available, including onabotulinumtoxinA Depending on the individual, treatment with onabotulinumtoxinA may require intermittent self-catheterization

10. Results with onabotulinumtoxinA last 10 months, which compares very favorably with use in other indications. Although onabotulinumtoxinA is indicated only for those who have failed or cannot tolerate anticholinergics, it is more effective than anticholinergics and is without the problematic side effects, such as dry mouth (and associated tooth decay), constipation, and cognitive effects, that can accompany anticholinergics Results with onabotulinumtoxinA last 10 months, which compares very favorably with use in other indications. Although onabotulinumtoxinA is indicated only for those who have failed or cannot tolerate anticholinergics, it is more effective than anticholinergics and is without the problematic side effects, such as dry mouth (and associated tooth decay), constipation, and cognitive effects, that can accompany anticholinergics Take-Home Messages