Phase 2b Study of the Clinical Efﬁcacy and Safety of Collagenase
Clostridium Histolyticum in Patients With Peyronie Disease
Martin Gelbard,*,† Larry I. Lipshultz,‡ James Tursi,§ Ted Smith,§ Greg Kaufman§
and Laurence A. Levine
From the Urology Associates Medical Group (MG), Burbank, California, Baylor College of Medicine (LIL), Houston, Texas, Auxilium
Pharmaceuticals, Inc. (JT, TS, GK), Malvern, Pennsylvania, and Rush University (LAL), Chicago, Illinois
Collagenase Clostridium histolyticum is an investigational nonsurgical
treatment for Peyronie disease. In this phase 2b, double-blind, randomized,
placebo controlled study we determined the safety and efﬁcacy of collagenase
C. histolyticum and assessed a patient reported outcome questionnaire.
Materials and Methods:
A total of 147 subjects were randomized into 4 groups to
receive collagenase C. histolyticum or placebo (3:1) with or without penile plaque
modeling (1:1). Per treatment cycle 2 injections of collagenase C. histolyticum
(0.58 mg) were given 24 to 72 hours apart. Subjects received up to 3 cycles at
6-week intervals. When designated, investigator modeling was done 24 to 72
hours after the second injection of each cycle. We evaluated penile curvature by
goniometer measurement, patient reported outcomes and adverse event proﬁles.
After collagenase C. histolyticum treatment signiﬁcant improvements
in penile curvature (29.7% vs 11.0%, p
0.001) and patient reported outcome
symptom bother scores (p
0.05) were observed compared to placebo. In
modeled subjects 32.4% improvement in penile curvature was observed in
those on collagenase C. histolyticum compared to 2.5% worsening of curvature
in those on placebo (p
0.001). Those treated with collagenase C. histolyticum
who underwent modeling also showed improved Peyronie disease symptom
bother scores (p
0.004). In subjects without modeling there were minimal
differences between the active and placebo cohorts. Most adverse events in the
collagenase C. histolyticum group occurred at the injection site and were mild
or moderate in severity. No treatment related serious adverse events were
Collagenase C. histolyticum treatment was well tolerated. We
noted signiﬁcant improvement in penile curvature and patient reported outcome
symptom bother scores, suggesting that this may be a safe, nonsurgical alterna-
tive for Peyronie disease.
penis; penile induration; collagenase VII-S, Clostridium
histolyticum; drug toxicity; questionnaires
based plaque in the tunica
albuginea associated with PD leads to
various penile malformations, includ-
ing curvature, indentation, narrow-
ing, shortening, hourglass-like shape
and buckling erection.
to physical symptoms, the psycholog-
ical impact of PD should be consid-
ered since studies show that many pa-
tients experience clinical depression,
emotional and relationship difﬁcul-
ties, and poor self-esteem.
gree of ED is also common in men with
Causes of ED may be physical due
International Index of
intent to treat
PD patient reported
treatment emergent AE
Submitted for publication August 22, 2011
Study received institutional review board ap-
proval at all sites.
Supported by Auxilium Pharmaceuticals.
* Correspondence: Urology Associates Medical
Group, 2601 West Alameda Ave., Suite 416, Bur-
bank, California 91505 (telephone: 818-843-1702;
FAX: 818-843-0380; e-mail:
† Financial interest and/or other relationship
with Auxilium and Biospeciﬁcs.
‡ Financial interest and/or other relationship
with Allergan, Auxilium, American Medical Sys-
tems and Repros Therapeutics.
§ Financial interest and/or other relationship
Financial interest and/or other relationship
with Auxilium, Coloplast, Lilly, Astellas, Pﬁzer
and American Medical Systems.
Vol. 187, 2268-2274, June 2012
THE JOURNAL OF UROLOGY
Printed in U.S.A.
© 2012 by A