We’re sorry. JavaScript is currently disabled in your browser, so you may not be able to fully experience the website. Please enable JavaScript to proceed.

The only treatment evaluated in 2 large multicenter studies of patients with Peyronie’s disease1

Studies 1 and 2* were randomized, double-blind, placebo-controlled, multicenter studies1,2

  • Studies 1 and 2 were published in The Journal of Urology as IMPRESS I and II (The Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies).
  • 551 received XIAFLEX®, 281 received placebo.1
  • All Intent-to-treat (ITT)=randomized men who received at least 1 dose of study drug.3,4
  • Modified intent-to-treat (mITT) population=patients with erectile curvature deformity measurement and Peyronie's Disease Questionnaire (PDQ) assessment at baseline, and at 1 or more subsequent time points, and who had engaged in vaginal intercourse within 3 months prior to each PDQ assessment.1

Study design

The efficacy of XIAFLEX® was evaluated in 2 randomized, double-blind, placebo-controlled, multicenter trials in 832 adult males with Peyronie’s disease (Studies 1 and 2). In these trials, patients were given up to 4 treatment cycles of XIAFLEX® or placebo (Weeks 0, 6, 12, 18), and were followed in a nontreatment follow-up period (Weeks 24–52). In each treatment cycle, 2 injections of XIAFLEX® or 2 injections of placebo were administered 1 to 3 days apart. A penile modeling procedure was performed 1 to 3 days after the second injection. The treatment cycle was repeated at ~6 week intervals for a maximum of 8 total injection procedures and 4 total modeling procedures. Patients also performed at-home penile modeling for 6 weeks.1

Before the first dose of study drug was administered, eligible patients were stratified by the degree of curvature deformity (30°–60°, and 61°–90°) and then randomized into 2 treatment groups to receive either XIAFLEX® or placebo in a 2:1 ratio.1

Study entry

  • In Studies 1 and 2, the co-primary endpoints were1:
    • The percentage change from baseline to Week 52 in erectile curvature deformity (erectile curvature)
    • The change from baseline to Week 52 in the Bother domain score of the PDQ
  • Patients must have had erectile curvature deformity of ≥30 degrees in the stable phase of Peyronie’s disease1
  • Patients were excluded if they had a ventral curvature deformity, an isolated hourglass deformity, or a calcified plaque that could have interfered with the injection technique1
    • A total of 156 patients presented with plaques that showed some calcification that did not interfere with the injection of XIAFLEX®, as identified using ultrasound or X-ray5
  • At baseline, penile pain was either not present or was mild in most (98%) patients1
  • At baseline, approximately 50% of patients in the XIAFLEX® clinical trials had a history of erectile dysfunction1

After up to 4 cycles of XIAFLEX®, improvement in erectile curvature from
baseline to Week 521

In Studies 1 and 2, mean percentage change in erectile curvature deformity from baseline to Week 521

STUDIES 1 & 2

A graph of clinical data results for Studies 1 and 2

Mean percentage change, treatment difference, 95% CI, and P value were based on an analysis of variance (ANOVA) model with factors for treatment, stratum of baseline erectile curvature, and their interaction and using last observation carried forward (LOCF) in the mITT population. The mITT population was defined as all randomized subjects who had both an erectile curvature deformity measurement and a PDQ assessment at baseline and at one or more subsequent time points.1

Study 1 Treatment Difference (95% CI): –17.2% (–26.7%, –7.6%).
Study 2 Treatment Difference (95% CI): –11.4% (–19.5%, –3.3%).1


Example of improvement in curvature deformity

If the curvature deformity is <15 degrees after the first, second, or third treatment cycle, or if the urologist determines that further treatment is not clinically indicated, then subsequent treatment cycles should not be administered.1

Significant reduction in Patient-Reported Bother1

What is Patient-Reported Bother domain score?

  • Co-primary endpoint in clinical trials was Patient-Reported Bother domain score change from baseline to Week 521
  • The Bother domain score is a composite of the following patient-reported items6-7:
    • Intercourse
    • Erection appearance
    • Erection pain
    • Intercourse frequency

Mean change in Patient-Reported Bother from baseline to Week 521

STUDY 1*

37.3%

reduction in Bother
from baseline or –2.8 points
with XIAFLEX®
N=199

21.6% reduction in
Bother from baseline or
–1.6 points with placebo
N=104

STUDY 2*

35.1%

reduction in Bother
from baseline or –2.6 points
with XIAFLEX®
N=202

18.3% reduction in
Bother from baseline or
–1.5 points with placebo
N=107

A reduction of ≥1 point in the Bother domain score was considered a response (with a ≥20% reduction in erectile curvature)8

Mean baseline Patient-Reported Bother scores1†

  • Study 1: XIAFLEX® 7.5; placebo 7.4
  • Study 2: XIAFLEX® 7.4; placebo 8.2

Study 1 Treatment Difference (95% CI): –1.2 (–2.4, –0.03); P<0.05. Study 2 Treatment Difference (95% CI): –1.1 (–2.1, –0.002); P<0.05.1

Mean change, treatment difference, 95% CI, and P value all based on an ANOVA model with factors for treatment, stratum of baseline erectile curvature, and their interaction and using LOCF in the mITT population.

The mITT population was defined as all randomized patients who had both an erectile curvature deformity measurement and a PDQ assessment at baseline and at one or more subsequent time points.1

Adverse reactions

Adverse reactions in Study 1 and Study 2 combined occurring in ≥1% treated with XIAFLEX® and also at a frequency greater
than placebo-treated patients after up to 4 treatment cycles1

  • Includes: injection-site hematoma and penile hematoma were reported with the verbatim term of penile bruising or injection-site bruising in 87% of patients.
  • Includes: injection-site swelling, penile edema, penile swelling, local swelling, scrotal swelling, and injection-site edema.
  • Includes: injection-site pain, penile pain, and injection-site discomfort.
  • Includes: contusion, ecchymoses, penile hemorrhage, and injection-site hemorrhage.
  • The majority of patients with Peyronie's disease experienced at least 1 adverse reaction (92% XIAFLEX®-treated patients, 61% placebo-treated patients)1
  • Most adverse reactions were local events of the penis and groin and the majority of these events were of mild or moderate severity, and most (79%) resolved within 14 days of the injection1
  • Severe penile hematoma or severe injection-site hematoma were reported in 33/551 (6.0%) of patients treated with XIAFLEX® and 0/281 (0%) of placebo-treated patients, in Studies 1 and 2 combined1
  • A popping noise or popping sensation in the penis, sometimes described as "snapping" or "cracking," and sometimes accompanied by detumescence, hematoma, and/or pain, was reported in 73/551 (13.2%) of patients treated with XIAFLEX® and 1/281 (0.3%) of placebo-treated patients1
View All
Collapse

Important Safety
Information for XIAFLEX®

WARNING: CORPORAL RUPTURE (PENILE FRACTURE) OR OTHER SERIOUS PENILE INJURY IN THE TREATMENT OF PEYRONIE'S DISEASE

Corporal rupture (penile fracture) was reported as an adverse reaction in 5 of 1044 (0.5%) XIAFLEX®‑treated patients in clinical studies. In other XIAFLEX®‑treated patients (9 of 1044; 0.9%), a combination of penile ecchymoses or hematoma, sudden penile detumescence, and/or a penile "popping" sound or sensation was reported, and in these cases, a diagnosis of corporal rupture cannot be excluded. Severe penile hematoma was also reported as an adverse reaction in 39 of 1044 (3.7%) XIAFLEX®‑treated patients.

Signs or symptoms that may reflect serious penile injury should be promptly evaluated to assess for corporal rupture or severe penile hematoma which may require surgical intervention.

Because of the risks of corporal rupture or other serious penile injury, XIAFLEX® is available for the treatment of Peyronie's disease only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XIAFLEX® REMS Program.

  • XIAFLEX® is contraindicated in the treatment of Peyronie's plaques that involve the penile urethra due to potential risk to this structure and in patients with a history of hypersensitivity to XIAFLEX® or to collagenase used in any other therapeutic application or application method
  • Injection of XIAFLEX® into collagen‑containing structures such as the corpora cavernosa of the penis may result in damage to those structures and possible injury such as corporal rupture (penile fracture). Therefore, XIAFLEX® should be injected only into the Peyronie's plaque and care should be taken to avoid injecting into the urethra, nerves, blood vessels, corpora cavernosa or other collagen‑containing structures of the penis
  • In the double‑blind, placebo‑controlled portions of the clinical trials in Peyronie's disease, a greater proportion of XIAFLEX®‑treated patients (4%) compared to placebo‑treated patients (1%) had localized pruritus after up to 4 treatment cycles (involving up to 8 XIAFLEX® injection procedures). The incidence of XIAFLEX®‑associated pruritus was similar after each injection regardless of the number of injections administered
  • Because XIAFLEX® contains foreign proteins, severe allergic reactions to XIAFLEX® can occur. Anaphylaxis was reported in a post‑marketing clinical trial in one patient who had previous exposure to XIAFLEX® for the treatment of Dupuytren's contracture. Healthcare providers should be prepared to address severe allergic reactions following XIAFLEX® injections. The safety of more than one treatment course of XIAFLEX® is not known
  • In the XIAFLEX® controlled trials in Peyronie’s disease, 65.5% of XIAFLEX®‑treated patients developed penile hematoma, and 14.5% developed penile ecchymosis. Patients with abnormal coagulation (except for patients taking low‑dose aspirin, eg, up to 150 mg per day) were excluded from participating in these studies. Therefore, the efficacy and safety of XIAFLEX® in patients receiving anticoagulant medications (other than low‑dose aspirin, eg, up to 150 mg per day) within 7 days prior to XIAFLEX® administration is not known. In addition, it is recommended to avoid use of XIAFLEX® in patients with coagulation disorders, including patients receiving concomitant anticoagulants (except for low‑dose aspirin)
  • In the XIAFLEX® clinical trials for Peyronie's disease, the most frequently reported adverse drug reactions (≥25%) and at an incidence greater than placebo included: penile hematoma, penile swelling, and penile pain

INDICATION

XIAFLEX® is indicated for the treatment of adult men with Peyronie's disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.

Please see the full Prescribing Information, including Boxed Warning and Medication Guide.

References:

1.  XIAFLEX® [package insert]. Malvern, PA: Endo Pharmaceuticals Inc.
2.  Gelbard M, Goldstein I, Hellstrom WJ, et al. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of Peyronie's disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol. 2013;190(1):199-207.
3.  Data on file. DOF-XPD-03. Endo Pharmaceuticals Inc; January 7, 2016.
4.  Data on file. DOF-XPD-04. Endo Pharmaceuticals Inc; January 7, 2016.
5.  Data on file. DOF-XDC-14. Endo Pharmaceuticals Inc; January 23, 2017.
6.  Data on file. DOF-XPD-02. Endo Pharmaceuticals Inc; September 21, 2015.
7.  Hellstrom WJ, Feldman R, Rosen RC, Smith T, Kaufman G, Tursi J. Bother and distress associated with Peyronie’s disease: validation of the Peyronie’s disease questionnaire. J Urol. 2013;190(2):627-634.
8.  Hellstrom WJ, Feldman RA, Coyne KS, et al. Self-report and clinical response to Peyronie’s disease treatment: Peyronie’s Disease Questionnaire results from 2 large double-blind, randomized, placebo-controlled phase 3 studies. Urology. 2015;86(2):291-298.