DISCUSSION

Treatment goals for PD are curvature reduction,

improved sexual function and a decrease in other

reported PD specific symptoms.

Results from this

phase 2b study revealed significant improvements

in penile curvature and PD symptom bother scores

with CCh treatment compared with placebo. The

safety results of this study indicate that CCh is well

tolerated with TEAEs or treatment related AEs that

were at most mild or moderate in severity and usu-

ally resolved without intervention.

There has been significant variability in study

design and lack of consistency in measuring and

interpreting outcomes in many PD series.

Clinical

objective measurements such as penile curvature

and length, etc, are difficult to make consistently

and there is operator dependent variation. To help

decrease variability penile curvature measurements

were standardized by cavernous injection of prosta-

glandin E1 to pharmacologically induce erection be-

fore measurement. However, since a fixed dose of

prostaglandin E1 was used, all subjects may not

have responded optimally, which could have been a

limiting factor. Also, investigators may have experi-

enced a brief learning curve with the injection tech-

nique, which may have affected the consistency of

results.

Physical and psychological symptoms associated

with PD should be considered when selecting a ther-

apeutic regimen. However, the lack of a standard

survey to assess PD specific symptoms was noted by

many experts, resulting in subsequent development

of the PD-PRO.

Data on the psychological impact of

PD shows that a significant number of patients pres-

ent with clinically meaningful depression, sometimes

severe emotional distress and low self-esteem.

Questions in the PD symptom bother domain of the

PD-PRO were designed to measure how bothered the

subject is by PD symptoms. Significant positive results

were observed after CCh treatment.

The goal of surgical correction of PD is to focally

improve the expansion of scarred tunica albuginea.

Intralesional injections of CCh enzymatically weaken

the plaque, which in conjunction with penile model-

ing may accomplish the same goal. In this study the

investigator modeled the flaccid penis in select pa-

tients. There was greater mean percent improve-

ment in penile curvature in those who underwent

physician modeling compared to the improvement in

penile curvature in those without modeling (32.4%

vs 27.1%) with no apparent increased risk to the

patient. Although the difference was not statisti-

cally significant, greater mean improvement was ob-

served with physician modeling.

Since spontaneous improvement in PD symptoms

is rare,

an unexpected study result was the high

placebo response in the group without modeling.

There was an imbalance among the groups in dis-

ease duration. The placebo group without modeling

had a higher percent of patients with a shorter dis-

ease history than any of the other groups. Possibly

some of these patients had not attained a steady state

of disease, resulting in spontaneous reduction of defor-

mity, which may have confounded the results. Due to

this imbalance and the few patients in the placebo

groups due to 3:1 randomization it is difficult to

determine the relevance of the higher than expected

placebo response.

CONCLUSIONS

CCh treatment provides significant improvement in

penile curvature and in the PD symptom bother

domain. CCh was well tolerated with no treatment

related SAEs. Results suggest that CCh should be

considered a viable treatment option for patients

with PD. Placebo controlled, phase 3 studies of PD

(NCT01221623 and NCT01221597) are currently

ongoing to provide additional safety and efficacy in-

formation.

ACKNOWLEDGMENTS

Dr. Jennifer Kent, MedVal Scientific Information

Services, assisted with the manuscript.

APPENDIX 1

Study Population Inclusion and Exclusion Criteria

Inclusion Criteria

Healthy, heterosexual males over age 18 in a stable relationship with a partner/spouse (for at least 3 months)

Diagnosis of PD for at least 6 months

Penile curvature of at least 30 degrees in the dorsal, lateral or dorsal/lateral plane (must have been possible to delineate the single plane of maximal curvature for

evaluation)

Functional difficulty related to PD (eg ED or difficulty with intromission)

Signed informed institutional review board approved consent agreement

Exclusion Criteria

Penile curvature of less than 30 or greater than 90 degrees

Calcified plaque as evident by appropriate radiographic evaluation, penile X-ray or penile ultrasound (noncontiguous stippling was allowed)

Isolated hourglass malformation of the penis without curvature

Plaque causing curvature of the penis located proximal to the base of the penis (injection of the local anesthesia would have interfered with the injection of CCH into

the plaque)

PHASE 2B STUDY OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM

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