1. Composite Responders Showed Improvement in Both
Penile Curvature Deformity and Symptom Bother
in Two Large Double-Blind, Randomized,
Placebo-Controlled Phase 3 Studies of Collagenase
Clostridium Histolyticum in the Treatment
of Peyronie’s Disease
Wayne JG Hellstrom1, Robert Feldman2, Ted Smith3,
Sue Hobson3, James Tursi3, Guy Bernstein4
1Tulane University Health Sciences Center, New Orleans, LA, USA;
2Connecticut Clinical Research Center and Urology Specialists, Middlebury,
CT, USA; 3Auxilium Pharmaceuticals, Chesterbrook, PA, USA;
4Urology Health Specialists, Bryn Mawr, PA, USA

2. Background
• In addition to the physical symptoms associated with PD, the
psychological impact of PD should also be considered during
the evaluation and treatment process
• Some studies have looked at the psychosocial impact of PD
on patients and found that many patients experience poor
self-image, emotional and relationship difficulties, and clinical
depression2-4
1Ralph D, et al. J Sex Med 2010;7:2359-74; 2Smith JF, et al. J Sex Med 2008;5:2179-84;
3Nelson CJ, et al. J Sex Med 2008;5:1985-90; 4Rosen R, et al. J Sex Med 2008;5:1977-84. 2
• Peyronie’s disease (PD) is a progressive
disease resulting in penile curvature
deformity that may be accompanied by
other symptoms, such as erectile
dysfunction and penile pain in the acute
phase of the disease1

3. Background (cont.)
• Placebo-controlled studies showing treatment efficacy are
limited for the majority of historically available minimally
invasive PD treatments1,2
• Collagenase clostridium histolyticum (CCH) is an investigational,
intralesional, minimally invasive treatment for PD
• In the largest studies conducted in subjects with PD to date, the
Investigation for Maximal Peyronie’s Reduction Efficacy and
Safety Studies (IMPRESS) I and II examined the clinical efficacy
of CCH compared with placebo in subjects with PD3
– Significant CCH treatment effects at Week 52 were found for the
co-primary outcomes:
» Improved penile curvature deformity
» Improved PD symptom bother domain score as measured using the
Peyronie's Disease Questionnaire (PDQ)
1Ralph D, et al. J Sex Med 2010;7:2359-74; 2Muller A, Mulhall JP. J Sex Med 2009;6:848-61;
3Gelbard M, et al. J Urol 2013 Jan 30. [Epub ahead of print] 3

4. Current Study Objective
• To examine the effect of CCH treatment compared
with placebo on the percentage of subjects with PD
in IMPRESS I and II who were composite responders
4
Composite Responder Definition:
Improvement in penile
curvature deformity
≥20%
Improvement in the
PDQ PD symptom
bother domain score of
≥1, or a change from
reporting no sexual
activity at screening to
reporting sexual activity
AND

5. Study Measures
• Objective measures of penile
curvature during chemically-induced
erection using a goniometer
– The point of maximal penile
curvature deformity was recorded
as the distance from the corona to
the maximum point of curvature
1Auxilium Pharmaceuticals. http://www.auxilium.com/PDQ. Accessed April 30, 2013;
2Hellstrom WJ, et al. J Urol 2013 Jan 31. [Epub ahead of print]
• The Peyronie’s Disease Questionnaire (PDQ)1
– A validated, disease-specific, self-administered, patient-
reported outcome instrument designed to measure the
symptoms and psychosexual impact of PD2
– The PDQ contains 3 domains that are scored individually
– Higher scores indicate a greater negative impact of PD
5

6. PDQ PD Symptom Bother Domain
PDQ PD Symptom Bother Domain Questions1*
Q10. Thinking about the last time you had an erection, how bothered were you by
any pain or discomfort you may have felt in your erect penis?
Q11. Thinking about the last time you looked at your erect penis, how bothered were
you by the way your penis looked?
Q13. Thinking of the last time you had or tried to have vaginal intercourse, how
bothered were you by your Peyronie’s disease?
Q15. How bothered are you with having vaginal intercourse less often?
*Q12 and Q14 (not shown) are “yes/no” screening questions and are not scored.
• PDQ PD symptom bother domain consists of 4 scored items and
2 “yes/no” questions that are not scored
• PD symptom bother severity is measured on a 5-point, Likert-type
response scale
– 0 (not at all bothered) to 4 (extremely bothered)
• Score for the PD symptom bother domain is calculated as the sum of all
responses and ranges from 0 to 16
1Auxilium Pharmaceuticals. http://www.auxilium.com/PDQ. Accessed April 30, 2013.
6

7. IMPRESS Treatment Schedule
Induction of Erection
Penile Curvature Measurement
Primary Plaque Identified
CCH or Placebo
Injection into
Primary Plaque
Subjects may receive up to 4 treatment cycles (up to 8 injections)
Each treatment cycle is separated by 6 weeks
CCH or Placebo
Injection into
Primary Plaque
Penile Plaque
Modeling
24-72 hours 24-72 hours
Treatment Cycle
7

8. Methods: Population and Data Used for Analysis
• Subjects had stable disease (≥12 months), penile
curvature deformity >30 to <90 , and vaginal
intercourse within the past 3 months (in order to
answer the PDQ questions)
• Data analysis:
– Baseline, Week 24, and Week 52 data from
IMPRESS I and II were combined
– Treatment groups were compared controlling for
stratum of baseline penile curvature deformity
(30 to 60 and 61 to 90 ) and study (IMPRESS I
or II)
8

9. IMPRESS Study Population
Baseline
Characteristics
CCH
(n=551)
Placebo
(n=281)
Age, years
Mean (SD) 57.6 (8.5) 57.9 (8.3)
Median 59 59
Min, Max 23, 84 30, 81
PD duration, years
Mean (SD) 4.1 (4.1) 4.1 (4.8)
Median 2.9 2.9
Min, Max 1.0, 35.9 1.0, 50.8
Penile curvature deformity, n (%)
30 to 60 425 (77.1) 218 (77.6)
60 to 90 126 (22.9) 63 (22.4)
9

10. Results: Percentage of Subjects With PD Who Were
Composite Responders at Weeks 24 and 52
• The group of men who received CCH treatment had a
significantly greater percentage of composite responders
compared with the placebo group at Week 24 and Week 52
(both P<0.0001)
48.8
26.5
46.6
28.0
0%
10%
20%
30%
40%
50%
60%
CCH Placebo
PercentageofComposite
Responders
Week 24
Week 52
10

11. Exploratory Outcome
• Using a more restrictive criterion of change in
the PDQ PD symptom bother domain score, the
percentage of composite responders was compared
in CCH-treated vs placebo-treated subjects
11
Exploratory Composite Responder Definition:
Improvement in penile
curvature deformity
≥20%
Improvement in the
PDQ PD symptom
bother domain score of
≥2, or a change from
reporting no sexual
activity at screening to
reporting sexual activity
AND

12. Results: Percentage of Subjects With PD Who Were
Composite Responders Using PD Bother Change ≥2
at Weeks 24 and 52
• Again, the group of men who received CCH treatment had a
significantly greater percentage of composite responders
compared with the placebo group at Week 24 and Week 52
(both P<0.0001)
44.1
23.8
41.8
24.2
0%
10%
20%
30%
40%
50%
CCH Placebo
PercentageofComposite
Responders
Week 24
Week 52
12

13. Conclusions
• A significantly greater percentage of CCH-treated PD subjects
compared with placebo-treated subjects met the definition of
composite responder
– Composite responders showed improvement in both penile
curvature deformity and PDQ PD symptom bother domain
score
• The significantly greater percentage of composite responders in
the CCH-treated subjects compared with placebo-treated
subjects was shown at Week 24 and remained consistent at
Week 52
• The greater percentage of composite responders in the CCH
treatment group compared with placebo remained when the
composite responder definition was made more stringent
• These findings support the clinical efficacy of CCH treatment
compared with placebo for both the physical and psychosexual
aspects of PD 13