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

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

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

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

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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

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

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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

IMPRESS Treatment Schedule

Induction of ErectionPenile Curvature MeasurementPrimary 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

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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)

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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)

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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)

CCH Placebo 0%

10%

20%

30%

40%

50%

60%

48.8

26.5

46.6

28.0

Week 24Week 52

Per

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esp

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s

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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

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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

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)

CCH Placebo 0%

10%

20%

30%

40%

50% 44.1

23.8

41.8

24.2

Week 24Week 52

Per

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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

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