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1659 INTRATUNICAL INJECTION OF ADIPOSE TISSUE-DERIVED STEM CELLS IN COMBINATION WITH HUMAN INTERFERON α-2B GENE THERAPY FOR PREVENTION AND TREATMENT OF ERECTILE DYSFUNCTION IN A RAT MODEL OF PEYRONIE'S DISEASE
Vol. 189, No. 4S, Supplement, Tuesday, May 7, 2013
THE JOURNAL OF UROLOGY姞
e683
1660 INTEGRATED SAFETY PROFILE OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN CLINICAL STUDIES EVALUATING THE TREATMENT OF PEYRONIE’S DISEASE Culley Carson, III*, Chapel Hill, NC; Hossein Sadeghi-Nejad, Hackensack, NJ; Ted Smith, Gregory Kaufman, Kimberly Gilbert, Malvern, PA; Stanton Honig, New Haven, CT
Source of Funding: Auxilium
1659 INTRATUNICAL INJECTION OF ADIPOSE TISSUE-DERIVED STEM CELLS IN COMBINATION WITH HUMAN INTERFERON ␣-2B GENE THERAPY FOR PREVENTION AND TREATMENT OF ERECTILE DYSFUNCTION IN A RAT MODEL OF PEYRONIE’S DISEASE Ahmet Gokce*, Zakaria Abd Elmageed, George Lasker, Sree Harsha Mandava, Landon Trost, Philip Kadowitz, Asim Abdel-Mageed, Suresh Sikka, Wayne Hellstrom, New Orleans, LA INTRODUCTION AND OBJECTIVES: Peyronie’s disease (PD) is a localized connective tissue disorder that affects the tunica albuginea of the penis. Characteristic inelastic scar tissue formation may dramatically diminish erectile function in PD. Intralesional treatments are growing in popularity as a minimally invasive approach in the initial treatment of PD. The aim of this study was to compare the efficacy of intratunical injection of adipose tissue-derived stem cells (ADSCs) vs. ADSCs in combination with human interferon ␣-2b gene therapy (ADSCs-IFN) for the treatment of ED in a rat model of PD. METHODS: A total of 36 male Sprague-Dawley rats (300-350 g) were randomly divided into six groups: sham (saline-injected into the TA); PD (transforming growth factor (TGF)-1 (50 g) injected into the TA); prevention groups (5x105 ADSCs or ADSCs-IFN injected into TA on the same day as TGF-1 injection); and treatment groups (5x105 ADSCs or ADSCs-IFN injected into TA 30 days after TGF-1 injection). Forty-five days following TGF-1 injection, rats underwent erectile function assessment by measuring the total intracavernous-to-mean arterial pressure ratio (ICP/MAP) and total ICP during cavernous nerve stimulation. RESULTS: The sham and PD groups had an ICP/MAP ratio of 48⫾9 compared to 18⫾2% (p⫽0.004) at 2.5 V, 64⫾7 compared to 45⫾6% at 5.0 V (p⫽0.04), and 79⫾3 compared to 72⫾3% at 7.5 V (p ⫽ 0.05). In the prevention groups significant improvement of erectile function were recorded at all stimulation parameters with ICP/MAP ratios of 72⫾5/72⫾4%, 78⫾3/77⫾1%, 85⫾2/82⫾2% at stimulation voltages of 2.5, 5.0 and 7.5 V for control ADSCs and ADSCs-IFN respectively (p ⬍ 0.05). In the treatment groups ICP/MAP ratios of 44⫾8/58⫾7%, 67⫾5/70⫾4%, 81⫾4/77⫾4% at stimulation voltages of 2.5, 5.0, and 7.5 V for ADSCs and ADSCs-IFN respectively (p ⬍ 0.05). Although the changes in ICP and AUC were higher in ADSCs-IFN vs. ADSCs in the treatment group, this difference was not statistically significant. CONCLUSIONS: Local injection of ADSCs in combination with human interferon ␣-2b gene therapy prevents and treats ED caused by PD. Regenerative medicine with combination of gene therapy in the field of PD is expected to evolve rapidly but further validation and study is required to assess their potential role in treatment of PD. Source of Funding: None
INTRODUCTION AND OBJECTIVES: Peyronie’s disease (PD) is a localized connective tissue disorder of the tunica albuginea of the penis in which a fibrous collagen scar or Peyronie’s plaque develops eventually developing a penile curvature deformity in many patients. Collagenase clostridium histolyticum (CCH) is a novel nonsurgical injection being studied for the treatment of PD. The objective of this study is to summarize the integrated safety of subjects who received at least one dose of CCH in 7 clinical studies (4 phase 2; 3 phase 3). METHODS: The safety database for CCH currently includes 954 PD subjects (6 completed studies and 1 interim) treated with at least one dose of CCH (0.58 mg) administered by injection in phase 2-3 clinical trials. The phase 2 studies (n⫽166) included up to 9 injections/ patient of CCH in varying treatment cycles. The phase 3 studies (n⫽788) included up to 8 injections/patient in 4 treatment cycles, each cycle consisting of 2 injections, with each cycle separated by approximately 6 weeks. RESULTS: The 954 subjects were treated with 6701 injections of CCH (0.58 mg) and 65.4% received 4 cycles of treatment (8 injections); 832 (87.2%) subjects completed their assigned study and 122 (12.8%) subjects prematurely discontinued. Of these, 17 subjects discontinued due to an adverse event (AE), of which 9 subjects discontinued for a nonserious AE considered treatment-related (mainly penile or injection site). At least one nonserious AE was reported by 893 (93.7%) subjects. All common AEs (⬎5% incidence) were either local to the penis, or at the injection site (Table 1). Fifty-eight (6.1%) subjects experienced at least one nonfatal serious AE (50 were not considered related to treatment). Eight subjects had at least one nonfatal serious AE considered to be related to CCH treatment (4 penile hematoma and 4 corporal rupture), resulting in interruption of treatment or drug withdrawal in 7 of 8 cases. There were no events of systemic hypersensitivity. There were 3 deaths among the CCH-treated population during the course of the studies but none were considered to be treatment-related. CONCLUSIONS: Our review of the safety of CCH in the treatment of PD shows that adverse experiences were predominantly nonserious and localized, and serious AEs were localized to the penis in these clinical studies.
Source of Funding: Auxilium Pharmaceuticals, Inc.
THE JOURNAL OF UROLOGY姞
e683
1660 INTEGRATED SAFETY PROFILE OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN CLINICAL STUDIES EVALUATING THE TREATMENT OF PEYRONIE’S DISEASE Culley Carson, III*, Chapel Hill, NC; Hossein Sadeghi-Nejad, Hackensack, NJ; Ted Smith, Gregory Kaufman, Kimberly Gilbert, Malvern, PA; Stanton Honig, New Haven, CT
Source of Funding: Auxilium
1659 INTRATUNICAL INJECTION OF ADIPOSE TISSUE-DERIVED STEM CELLS IN COMBINATION WITH HUMAN INTERFERON ␣-2B GENE THERAPY FOR PREVENTION AND TREATMENT OF ERECTILE DYSFUNCTION IN A RAT MODEL OF PEYRONIE’S DISEASE Ahmet Gokce*, Zakaria Abd Elmageed, George Lasker, Sree Harsha Mandava, Landon Trost, Philip Kadowitz, Asim Abdel-Mageed, Suresh Sikka, Wayne Hellstrom, New Orleans, LA INTRODUCTION AND OBJECTIVES: Peyronie’s disease (PD) is a localized connective tissue disorder that affects the tunica albuginea of the penis. Characteristic inelastic scar tissue formation may dramatically diminish erectile function in PD. Intralesional treatments are growing in popularity as a minimally invasive approach in the initial treatment of PD. The aim of this study was to compare the efficacy of intratunical injection of adipose tissue-derived stem cells (ADSCs) vs. ADSCs in combination with human interferon ␣-2b gene therapy (ADSCs-IFN) for the treatment of ED in a rat model of PD. METHODS: A total of 36 male Sprague-Dawley rats (300-350 g) were randomly divided into six groups: sham (saline-injected into the TA); PD (transforming growth factor (TGF)-1 (50 g) injected into the TA); prevention groups (5x105 ADSCs or ADSCs-IFN injected into TA on the same day as TGF-1 injection); and treatment groups (5x105 ADSCs or ADSCs-IFN injected into TA 30 days after TGF-1 injection). Forty-five days following TGF-1 injection, rats underwent erectile function assessment by measuring the total intracavernous-to-mean arterial pressure ratio (ICP/MAP) and total ICP during cavernous nerve stimulation. RESULTS: The sham and PD groups had an ICP/MAP ratio of 48⫾9 compared to 18⫾2% (p⫽0.004) at 2.5 V, 64⫾7 compared to 45⫾6% at 5.0 V (p⫽0.04), and 79⫾3 compared to 72⫾3% at 7.5 V (p ⫽ 0.05). In the prevention groups significant improvement of erectile function were recorded at all stimulation parameters with ICP/MAP ratios of 72⫾5/72⫾4%, 78⫾3/77⫾1%, 85⫾2/82⫾2% at stimulation voltages of 2.5, 5.0 and 7.5 V for control ADSCs and ADSCs-IFN respectively (p ⬍ 0.05). In the treatment groups ICP/MAP ratios of 44⫾8/58⫾7%, 67⫾5/70⫾4%, 81⫾4/77⫾4% at stimulation voltages of 2.5, 5.0, and 7.5 V for ADSCs and ADSCs-IFN respectively (p ⬍ 0.05). Although the changes in ICP and AUC were higher in ADSCs-IFN vs. ADSCs in the treatment group, this difference was not statistically significant. CONCLUSIONS: Local injection of ADSCs in combination with human interferon ␣-2b gene therapy prevents and treats ED caused by PD. Regenerative medicine with combination of gene therapy in the field of PD is expected to evolve rapidly but further validation and study is required to assess their potential role in treatment of PD. Source of Funding: None
INTRODUCTION AND OBJECTIVES: Peyronie’s disease (PD) is a localized connective tissue disorder of the tunica albuginea of the penis in which a fibrous collagen scar or Peyronie’s plaque develops eventually developing a penile curvature deformity in many patients. Collagenase clostridium histolyticum (CCH) is a novel nonsurgical injection being studied for the treatment of PD. The objective of this study is to summarize the integrated safety of subjects who received at least one dose of CCH in 7 clinical studies (4 phase 2; 3 phase 3). METHODS: The safety database for CCH currently includes 954 PD subjects (6 completed studies and 1 interim) treated with at least one dose of CCH (0.58 mg) administered by injection in phase 2-3 clinical trials. The phase 2 studies (n⫽166) included up to 9 injections/ patient of CCH in varying treatment cycles. The phase 3 studies (n⫽788) included up to 8 injections/patient in 4 treatment cycles, each cycle consisting of 2 injections, with each cycle separated by approximately 6 weeks. RESULTS: The 954 subjects were treated with 6701 injections of CCH (0.58 mg) and 65.4% received 4 cycles of treatment (8 injections); 832 (87.2%) subjects completed their assigned study and 122 (12.8%) subjects prematurely discontinued. Of these, 17 subjects discontinued due to an adverse event (AE), of which 9 subjects discontinued for a nonserious AE considered treatment-related (mainly penile or injection site). At least one nonserious AE was reported by 893 (93.7%) subjects. All common AEs (⬎5% incidence) were either local to the penis, or at the injection site (Table 1). Fifty-eight (6.1%) subjects experienced at least one nonfatal serious AE (50 were not considered related to treatment). Eight subjects had at least one nonfatal serious AE considered to be related to CCH treatment (4 penile hematoma and 4 corporal rupture), resulting in interruption of treatment or drug withdrawal in 7 of 8 cases. There were no events of systemic hypersensitivity. There were 3 deaths among the CCH-treated population during the course of the studies but none were considered to be treatment-related. CONCLUSIONS: Our review of the safety of CCH in the treatment of PD shows that adverse experiences were predominantly nonserious and localized, and serious AEs were localized to the penis in these clinical studies.
Source of Funding: Auxilium Pharmaceuticals, Inc.