For men with Peyronie’s disease, there’s good news. XIAFLEX.drurydesignaux.weebly.com/uploads/2/6/4/3/26438379/... · 2020. 1. 26. · Important Safety Information Corporal rupture

Important Safety InformationCorporal rupture was reported as a serious adverse event after XIAFLEX injection in 4 patients (0.4%) in the controlled and uncontrolled clinical trials in Peyronie’s disease. Injection of XIAFLEX into collagen-containing structures of the penis may result in damage to those structures and possible injury such as corporal rupture (penile fracture)

Please see Important Safety Information on page 8, and full Prescribing Information and Medication Guide in back pocket.

For men with Peyronie’s disease, there’s good news. XIAFLEX.

XIAFLEX® is indicated for Peyronie’s disease in men with curvature deformity of ≥30° at the start of therapy

FPO



For men with Peyronie’s disease, there’s good news: an FDA-approved treatment option.

XIAFLEX.


FPO



For men with Peyronie’s disease, there’s good news.


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• In vitro studies suggest XIAFLEX selectively disrupts 2 predominant types of collagen found in Peyronie’s plaque without causing changes to the noncollagenous structures

• Following enzymatic disruption of Peyronie’s plaque collagen, penile curvature deformity and Patient Bother caused by Peyronie’s disease are reduced

Studies 1 and 2 (submitted for publication as IMPRESS I and II*) evaluated 832 men with Peyronie’s disease over the course 52 weeks • Eligible subjects were randomized (in 2:1 ratio) into 2 treatment groups – 551 treated with XIAFLEX – 281 treated with placebo

The modified ITT (mITT) population was defined as all ITT subjects who were both in the PDQ and PM populations. The PDQ population was defined as all ITT subjects who had a non-missing Peyronie’s Patient-Reported Bother score at screening and who also had a nonmissing Peyronie’s Patient-Reported Bother score post the first injection of the study drug. The PM population was defined as all ITT subjects who had a curvature deformity measurement at screening and who also had at least one curvature deformity measurement post the first injection of the study drug.

• Percent improvement in penile curvature deformity

• Change in the Patient-Reported Bother domain of the Peyronie’s Disease Questionnaire (PDQ) – Patient-Reported Bother included measures of concern about:

Impact of Peyronie’s disease during vaginal intercourse

Erection pain or discomfort

Important Safety Information • In the double-blind, placebo-controlled portions of the clinical trials in Peyronie’s disease

(Studies 1 and 2), 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

Formation of Peyronie’splaque collagen

Peyronie’s plaque

Injection with XIAFLEX may enzymatically disrupt Peyronie’s plaque collagen

Study entry

• Patients must have had penile curvature deformity in the stable phase of Peyronie’s disease

• 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 technique

Treatment protocol†

• Patients were given up to 4 treatment cycles of XIAFLEX or placebo at weeks 0, 6, 12, and 18

• 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 on patients

at the study site 1 to 3 days after the second injection of the cycle

• Patients were instructed to perform penile modeling at home for 5-6 weeks after each treatment cycle

• Patients were followed in a nontreatment follow-up period from weeks 24 through 52

XIAFLEX® (collagenase clostridium histolyticum) helps disrupt Peyronie’s plaque collagen

Efficacy of XIAFLEX® proven in 2 randomized, double- blind, placebo-controlled, multicenter studies

Erection appearance

Intercourse frequency

XIAFLEX is the first and only FDA-approved treatment proven effective for Peyronie’s disease in men with curvature deformity of ≥30° at the start of therapy


IndicationXIAFLEX is indicated for Peyronie’s disease in men with curvature deformity of ≥30° at the start of therapy

Important Safety Information • In the XIAFLEX trials in Peyronie’s disease (Studies

1 and 2), 80% of XIAFLEX-treated patients developed penile ecchymosis

• 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

• Therefore, use with caution in patients with coagulation disorders including patients receiving concomitant anticoagulants (except for low-dose aspirin)

Peyronie’s plaque electron micrograph of collagen fibers

X = Disruption

*IMPRESS = The Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies.†See full treatment protocol on page 10.

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Illustration is intended to demonstrate 20,000x magnification

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• In vitro studies suggest XIAFLEX selectively disrupts 2 predominant types of collagen found in Peyronie’s plaque without causing changes to the noncollagenous structures

• Following enzymatic disruption of Peyronie’s plaque collagen, penile curvature deformity and Patient Bother caused by Peyronie’s disease are reduced

Studies 1 and 2 (submitted for publication as IMPRESS I and II*) evaluated 832 men with Peyronie’s disease over the course 52 weeks • Eligible subjects were randomized (in 2:1 ratio) into 2 treatment groups – 551 treated with XIAFLEX – 281 treated with placebo

The modified ITT (mITT) population was defined as all ITT subjects who were both in the PDQ and PM populations. The PDQ population was defined as all ITT subjects who had a non-missing Peyronie’s Patient-Reported Bother score at screening and who also had a nonmissing Peyronie’s Patient-Reported Bother score post the first injection of the study drug. The PM population was defined as all ITT subjects who had a curvature deformity measurement at screening and who also had at least one curvature deformity measurement post the first injection of the study drug.

• Percent improvement in penile curvature deformity

• Change in the Patient-Reported Bother domain of the Peyronie’s Disease Questionnaire (PDQ) – Patient-Reported Bother included measures of concern about:

Impact of Peyronie’s disease during vaginal intercourse

Erection pain or discomfort

Important Safety Information • In the double-blind, placebo-controlled portions of the clinical trials in Peyronie’s disease

(Studies 1 and 2), 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)


Formation of Peyronie’splaque collagen

Peyronie’s plaque

Injection with XIAFLEX may enzymatically disrupt Peyronie’s plaque collagen

Study entry

• Patients must have had penile curvature deformity in the stable phase of Peyronie’s disease

• 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 technique

Treatment protocol†

• Patients were given up to 4 treatment cycles of XIAFLEX or placebo at weeks 0, 6, 12, and 18

• 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 on patients

at the study site 1 to 3 days after the second injection of the cycle

• Patients were instructed to perform penile modeling at home for 5-6 weeks after each treatment cycle

• Patients were followed in a nontreatment follow-up period from weeks 24 through 52

XIAFLEX® (collagenase clostridium histolyticum) helps disrupt Peyronie’s plaque collagen

Efficacy of XIAFLEX® proven in 2 randomized, double- blind, placebo-controlled, multicenter studies

Erection appearance

Intercourse frequency



Important Safety Information • In the XIAFLEX trials in Peyronie’s disease (Studies

1 and 2), 80% of XIAFLEX-treated patients developed penile ecchymosis

• 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

• Therefore, use with caution in patients with coagulation disorders including patients receiving concomitant anticoagulants (except for low-dose aspirin)

Peyronie’s plaque electron micrograph of collagen fibers

X = Disruption

*IMPRESS = The Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies.†See full treatment protocol on page 10.

FPO

FPO

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Illustration is intended to demonstrate 20,000x magnification

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• Continuous improvement in penile curvature deformity was demonstrated during the 24-week treatment period

• Improvement was maintained during the nontreatment follow-up period, weeks 24 through 52Before the first dose of XIAFLEX® (collagenase clostridium histolyticum) was administered: • Mean baseline measurements of penile curvature deformity were – Study 1: 48.8° for XIAFLEX (N=199); 49.0° for placebo (N=104) – Study 2: 51.3° for XIAFLEX (N=202); 49.6° for placebo (N=107)

• Subjects were randomized into 2 treatment groups to receive either XIAFLEX or placebo in a 2:1 ratio

• Eligible subjects were stratified by degree of baseline curvature deformity (30° to 60° or 61° to 90°)

– The improvement in penile curvature deformity between these groups was similar

Important Safety Information • In the double-blind, placebo-controlled portions of the clinical trials in Peyronie’s disease (Studies 1 and 2),

a greater proportion of patients treated with XIAFLEX (4%) compared to placebo-treated patients (1%) had localized pruritus after up to 4 treatment cycles (involving up to 8 XIAFLEX injection procedures)




Important Safety Information • Healthcare providers should be prepared to address severe allergic reactions following XIAFLEX injections

• Although there were no severe allergic reactions observed in the XIAFLEX studies (eg., those associated with respiratory compromise, hypotension, or end-organ dysfunction), severe reactions including anaphylaxis could occur following XIAFLEX injections

Significant improvement in penile curvature deformity Sustained improvements in penile curvature deformity at Week 52

Data are from the 2 IMPRESS trials. Following treatment with XIAFLEX compared to a placebo, P values are based on an last observation carried forward (LOCF) analysis at week 52.

Images represent a 33% change from baseline

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*Last observation carried forward (LOCF).†Patients were given up to 4 treatment cycles of XIAFLEX or placebo at weeks 0, 6, 12, 18.‡p-values based on an ANOVA with factors for drug, stratum of baseline curvature deformity, and their interaction.

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XIAFLEX® (collagenase clostridium histolyticum) also reduced Patient-Reported Bother

In a secondary endpoint compared with placebo– Overall improvement in Global Assessment scores

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Men may experience bother, even with a minimal penile curvature deformity.*

Patient-Reported Bother was assessed using the Peyronie’s Disease Questionnaire (PDQ), a validated 6-question tool that measures bother associated with

• Impact of Peyronie’s disease during vaginal intercourse

• Erection pain or discomfort

• Erection appearance

• Intercourse frequency

Important Safety Information • The most frequently reported adverse drug reactions (≥5%) in the XIAFLEX clinical trials at an incidence greater

than placebo in patients with Peyronie’s disease included: penile ecchymosis, penile swelling, and penile pain

All data for penile curvature deformity and bother are from a modified intent-to-treat (mITT) last observation carried forward (LOCF) analysis at Week 52. Patient-Reported Bother is one of 2 primary endpoints of the 2 pivotal clinical studies for XIAFLEX. P values are based on an LOCF analysis at Week 52 and an analysis of variance (ANOVA) with factors for drug, stratum of baseline penile curvature deformity, and their interaction.

Significantly more men reported an overall improvement in Global Assessment scores

• Global Assessment scores measured the “symptoms and effects of Peyronie’s disease in their life”

• Subjects who reported improvement from their symptoms and effects, rated themselves as “much improved,” “moderately improved,” or “improved in a small but important way”, and had

– A mean improvement of at least 20% from baseline in curvature deformity and – A mean reduction from baseline of at least one point in their Peyronie’s disease Bother domain score


Important Safety Information • Penile hematoma was reported as a serious local adverse reaction

associated with XIAFLEX treatment in 5 patients (0.5%) in the controlled and uncontrolled clinical studies in Peyronie’s disease


N=401

N=211

29.5% of patientsreported improvement

P<.0001

60.8% of patients reported improvementXIAFLEX

Placebo

Percentage of men reporting overall improvement in Global Assessment scores at Week 52

•Baseline Patient-Reported Bother scores - Study 1: Xiaflex - 7.5; Placebo - 7.4 - Study 2: Xiaflex - 7.4; Placebo - 8.2

•Patient-Reported Bother score range: 0-16 (higher numbers represent greater bother)

* In Studies 1 and 2, subjects with a curvature deformity of 30° to 60º at baseline had as much bother as those with curvature deformity of 61º to 90° at baseline.

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XIAFLEX is indicated for Peyronie’s disease in men with curvature deformity of ≥30° at the start of therapy

Important Safety Information • Corporal rupture was reported as a serious adverse event after XIAFLEX injection in 4 patients (0.4%) in the controlled and uncontrolled clinical trials in Peyronie’s disease.

• Injection of XIAFLEX into collagen-containing structures 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

• Penile hematoma was also reported as a serious local adverse reaction associated with XIAFLEX treatment in 5 patients (0.5%) in the controlled and uncontrolled clinical studies in Peyronie’s disease

• In the double-blind, placebo-controlled portions of the clinical trials in Peyronie’s disease (Studies 1 and 2), 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

• Although there were no severe allergic reactions observed in the XIAFLEX studies (eg., those associated with respiratory compromise, hypotension, or end-organ dysfunction), severe reactions including anaphylaxis could occur following XIAFLEX injections. Healthcare providers should be prepared to address severe allergic reactions following XIAFLEX injections

• In the XIAFLEX trials in Peyronie’s disease (Studies 1 and 2), 80% of XIAFLEX-treated patients developed penile ecchymosis

• 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. Therefore, use with caution in patients with coagulation disorders, including patients receiving concomitant anticoagulants (except for low-dose aspirin)

• The most frequently reported adverse drug reactions (≥5%) in the XIAFLEX clinical trials at an incidence greater than placebo in patients with Peyronie’s disease included: penile ecchymosis, penile swelling, and penile pain

Most adverse reactions were local events of the penis and groin and included penile ecchymosis, penile swelling, and penile pain.

Adverse reactions occurring in ≥1% of patients treated with XIAFLEX*

Important Safety Information about XIAFLEX® (collagenase clostridium histolyticum)

Please see full Prescribing Information and Medication Guide in back pocket.

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XIAFLEX should be administered by a healthcare provider (HCP) experienced in the treatment of male urological diseases.

Treating with XIAFLEX® (collagenase clostridium histolyticum)


• Injection of XIAFLEX into collagen-containing structures 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


XIAFLEX can be administered in the office: • A treatment cycle consists of 3 office visits over

the course of 3 to 7 days

• During the first and second office visits, XIAFLEX is injected into the Peyronie’s plaque collagen

• During the third office visit, the HCP performs modeling that stretches and elongates the plaque

– This procedure helps relieve penile curvature deformity and straighten the penile shaft XIAFLEX has an established

HCPCS code-J0775.

CPT* code 54200 is available for the injection procedure.


Important Safety Information • Penile hematoma was also reported as a serious local adverse reaction associated with XIAFLEX treatment in 5 patients

(0.5%) in the controlled and uncontrolled clinical studies in Peyronie’s disease

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Getting started with XIAFLEX®

*CPT is a registered trademark of the American Medical Association.

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For patients

- Provides financial assistance for XIAFLEX prescriptions (through Patient Assistance or Co-payment Program) for qualified patients

- Notifies patients of financial obligations

For HCPs and their practice

- Focuses on coverage, acquisition, reimbursement, and patient co-payment assistance

- Assists with insurance coverage/benefits research and verification

- Coordinates with HCP to schedule drug shipment

- Offers educational resources on Proper administration of XIAFLEX Acquisition of XIAFLEX through Specialty

Pharmacies

Auxilium Advantage is committed to your patient’s access to XIAFLEX

- Provides a single point of contact for HCPs and patients, to support patient access from start to finish

After the third office visit of each treatment cycle, the patient performs 5 to 6 weeks of at-home daily penile modeling exercises that involve both stretching and straightening the penis.

Four treatment cycles may be administered per plaque.

For complete details on the Dosing and Administration of XIAFLEX, please see the full Prescribing Information.

Significant improvement in penile curvature deformity compared with placebo, with improvement sustained at Week 52.

Significant results reported by patients in pivotal studies

• Significant reduction in Patient-Reported Bother compared with placebo

• Significantly greater percentage of patients reported overall improvement in Global Assessment scores measuring the symptoms and effects of Peyronie’s disease compared with placebo

J0775 is the dedicated HCPCS code for XIAFLEX

Once the decision to prescribe XIAFLEX is made, Auxilium AdvantageTM can assist your patient with • Insurance benefit investigation • Prior authorization • Specialty pharmacy services • Patient financial assistance for those who qualify


Important Safety Information

• In the XIAFLEX trials in Peyronie’s disease (Studies 1 and 2), 80% of XIAFLEX-treated patients developed penile ecchymosis

• 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. Therefore, use with caution in patients with coagulation disorders, including patients receiving concomitant anticoagulants (except for low-dose aspirin)

© 2013 Auxilium Pharmaceuticals, Inc. XPD-00225

Please see Important Safety Information on page 8, and full Prescribing Information and Medication Guide in back pocket.12


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– This procedure helps relieve penile curvature deformity and straighten the penile shaft

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XIAFLEX has an established HCPCS code-J0775.


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For patients








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Up to 4 treatment cycles may be administered per plaque

• For the 5- to 6-week period between each treatment cycle

- The patient performs at-home daily penile modeling exercises that involve both stretching and straightening the penis

- For complete details on the Dosing and Administration of XIAFLEX, please see the full Prescribing Information






XIAFLEX can be administered in the office: • A treatment cycle consists of 3 office visits over the course of 3 to 7 days




ALT 4 10-11



FPO


Important Safety Information • Penile hematoma was also reported as a serious local adverse reaction associated with XIAFLEX treatment in 5 patients (0.5%)

in the controlled and uncontrolled clinical studies in Peyronie’s disease

XIAFLEX TREATMENT CYCLE

Patient at-home

daily, penile modeling

5 to

6 w

eeks

In-officepenile modeling

procedure

1ST

In-officeinjection

1 to 3 days

2ND

In-officeinjection

UP TO 4 TREATMENT

CYCLES

1 to

3 da

ys



TM

TM

For patients








Pharmacies

Auxilium Advantage is committed to your patient’s access to XIAFLEX - Provides a single point of contact for HCPs and patients, to

support patient access from start to finish

Documents

For men with Peyronie’s disease, there’s good news. XIAFLEX.drurydesignaux.weebly.com/uploads/2/6/4/3/26438379/... · 2020. 1. 26. · Important Safety Information Corporal rupture