JUVÉDERM® Family of Hyaluronic Acid

Fillers

The only HA filler FDA approved† to last up to1 year with initial treatment1,2,‡

The first and only smooth-consistency gel formulated with lidocaine

Provides a more comfortable patient experience1-3,*

2

JUVÉDERM® XC Sets the Standard

FDA = US Food and Drug Administration; HA = hyaluronic acid.*When compared to the nonlidocaine JUVÉDERM® formulations.†In the United States, JUVÉDERM® injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds). ‡This includes all JUVÉDERM® injectable gel formulations. 1. JUVÉDERM® Ultra XC Directions for Use; 2. JUVÉDERM® Ultra Plus Directions for Use; 3. Weinkle et al. J Cosmet Dermatol. 2009.

JUVÉDERM® XC Possesses Unique Physical and Chemical Properties¹

• HYLACROSS™ technology: robust and smooth consistency1

– Proprietary cross-linking and homogenization– Uniform extrusion force and smooth flow– Random sizes and shapes that result in a smooth-consistency gel– Results in a unique 3D matrix that is strong and robust, yet

still soft and smooth

3

Less cross-linked Granular consistency

Competitive HA fillers

Smooth consistency

JUVÉDERM®

More cross-linked

The significance of the difference has not been established in controlled clinical studies.1. Data on file, Allergan, Inc.; JUVÉDERM® Technical File.

Adding Lidocaine as a Dry Substance Ensures the Same Chemical and Physical Characteristics asJUVÉDERM® Injectable Gel Without Lidocaine

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• Addition of lidocaine has no effect on1,2:– HA concentration or volume – Product viscosity or extrusion force– HA degradation – pH level

1. Weinkle et al. J Cosmet Dermatol. 2009; 2. Data on file, Allergan, Inc.

Chemical/PhysicalChemical/Physical TestTestJUVÉDERMJUVÉDERM®® Injectable Gel Injectable Gel With and Without LidocaineWith and Without Lidocaine

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Functional Equivalence Between JUVÉDERM® and JUVÉDERM® XC

• Lidocaine, when added as dry substance, does not increase the volume of the gel, dilute the HA content, or interfere with HAcross-linking1,2

• Lidocaine is rapidly released from the gel and metabolized after the dermal filler is injected1,2

Susceptibility to degradation• Enzymatic• Free radical

Equivalent

Rheologic properties Equivalent

pH Equivalent

Extrusion force Equivalent

1. Weinkle et al. J Cosmet Dermatol. 2009; 2. Data on file, Allergan, Inc.

JUVÉDERMJUVÉDERM

®® Ultra Ultra

JUVÉDERMJUVÉDERM

®® Ultra XCUltra XC

JUVÉDERMJUVÉDERM

®® Ultra PlusUltra Plus

JUVÉDERMJUVÉDERM

®® Ultra Ultra

Plus XCPlus XC

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Summary of JUVÉDERM® Physicaland Chemical Properties¹

Lidocaine concentration NA 0.3% NA 0.3%

Total HA concentration 24 mg/mL 24 mg/mL 24 mg/mL 24 mg/mL

Percentageuncross-linked HAa ~10% ~10% ~10% ~10%

Degree of cross-linking ~6% ~6% ~8% ~8%

FormulationSmooth

cohesive gelSmooth

cohesive gelSmooth

cohesive gelSmooth

cohesive gel

Needle 30 G 30 G 27 G 27 G

aUncrosslinked HA is defined as the portion of the product including lightly cross-linked chains and fragments that will aid extrusion/flow.1. Data on file. Allergan, Inc; JUVÉDERM® Technical File.

JUVÉDERM® XC Pivotal Study:Comparison of Effectiveness and SafetyWith JUVÉDERM®¹

7

NLF = nasolabial fold.1. Weinkle et al. J Cosmet Dermatol. 2009.

Multicenter, double-blind, randomized, within subject comparison

• 72 subjects total (18 subjects at each center)• 4 study centers

Randomization

• JUVÉDERM® XC in 1 NLF• JUVÉDERM® (without lidocaine) in the opposite NLF

Protocol

• Use of dental block was not permitted in the study• Investigators determined appropriate formulation (JUVÉDERM® Ultra or

JUVÉDERM® Ultra Plus) and filler volume up to a maximum total volume of 2 syringes (1.6 mL) per NLF

Subject Diary for CTRsSubject Diary for CTRs

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JUVÉDERM® XC Study Flowand Assessments¹

Day 2(Phone/e-mail)

Day 14(Office visit)

JUVÉDERM®® treatmenttreatment

Treatment:Treatment:Randomization,

injection volume, technique

Subject Assessment:Subject Assessment:Procedural pain score

Comparative procedural pain scoreNLF Severity Scale (NLFSS)

Investigator Assessment:Investigator Assessment:CTRs

Day 0

Investigator Day 14 Investigator Day 14 Assessment:Assessment:

NLF Severity Scale (NLFSS)

Investigator Baseline Investigator Baseline Assessment:Assessment:

NLF Severity Scale (NLFSS)

Investigator Assessment:Investigator Assessment:Common treatment-site

responses (CTRs)

1. Weinkle et al. J Cosmet Dermatol. 2009.

Subject Assessment:Subject Assessment:NLF Severity Scale (NLFSS)

Secondary: Comparative Procedural Pain Scale (CPPS)Secondary: Comparative Procedural Pain Scale (CPPS)Subjects compared procedural pain between the right and left NLF;5-point scale immediately and within 30 minutes after both sides were treated

Secondary: NLF Severity Scale (NLFSS)Secondary: NLF Severity Scale (NLFSS)Investigators and subjects rated NLF severity;5-point scale at pretreatment and day 14

Primary: Procedural PainPrimary: Procedural PainSubjects rated pain during injection;0–10 scale within 30 minutes after both sides were treated

9JUVÉDERM® XC Subject and Investigator Effectiveness Assessments¹

0No pain

1 2 3 4 5 6 7 8 910

Worst pain imaginable

0 None

1 Mild

2Moderate

3Severe

4 Extreme

-2 Right more painful

-1 Right slightly more

painful

0 No difference

1 Left slightly more

painful

2 Left more painful

1.Weinkle et al. J Cosmet Dermatol. 2009.

JUVÉDERM® XC Subject and Investigator Safety Assessments¹

• Subjects maintained diary records using a validated interactive voice response system (IVRS) for 2 weeks to track CTRs

• Subjects reported absence or presence, severity, and location (right or left NLF) of the most common CTRs

• Subjects also reported and investigators solicited additional CTRs

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CTR = common treatment-site response1.Weinkle et al. J Cosmet Dermatol. 2009; 2. Data on file, Allergan, Inc.

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JUVÉDERM® XC Provides a MoreComfortable Patient Experience1-3

*When compared to the nonlidocaine JUVÉDERM® formulations.†For the primary measure, the absolute mean difference in pain score (3.4) exceeds the minimum clinically significant difference of 1.4 established a priori,which demonstrates a clinically meaningful difference in pain for JUVÉDERM® with lidocaine1. JUVÉDERM® Ultra XC Directions for Use; 2. JUVÉDERM® Ultra Plus Directions for Use; 3. Weinkle et al. J Cosmet Dermatol. 2009.

More Than 90% of the SubjectsReported Less Treatment Pain

With JUVÉDERM® XC1-3,*

More painful 3%Slightly more painful

64%64%

29%29%Slightlyless painful

4%4%With Lidocaine Without Lidocaine

JUVÉDERM® XC Provides SignificantReduction in Pain Compared WithJUVÉDERM® Without Lidocaine1-3,*

P < .001 (N=72)

63%reduction

(N = 72)Less painful

With the Exception of Pain and Tenderness, CTRs Were Similar for All JUVÉDERM® Formulations1-3

• Most CTRs were mild to moderate in severity and were consistent with those typical of HA fillers

– Pain and tenderness were significantly reduced for JUVÉDERM® XC

– No subject reported severe pain for JUVÉDERM® XC

• There were no adverse events other than CTRs related to treatment

• The potential for allergic reactions to lidocaine is reduced due to the use of preservative-free powder4

12

1.JUVÉDERM® Ultra XC Directions for Use; 2. JUVÉDERM® Ultra Plus Directions for Use; 3. Weinkle et al. J Cosmet Dermatol. 2009;4. Jackson et al. J Am Dent Assoc. 1994 .  

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Summary of JUVÉDERM® XCRegistration Trial

*When compared to the nonlidocaine formulations.1. Weinkle SM et al. J Cosmet Dermatol. 2009.

Effectiveness

• 9 out of 10 patients reported less pain with JUVÉDERM® XC1,*

• Patient assessment of procedural pain with JUVÉDERM® XC averaged 2.0(compared with an average of 5.4 without lidocaine) on an 11-point scale (0 = no pain and 10 = worst pain imaginable)1

• NLF severity was significantly improved with both JUVÉDERM® XC and nonlidocaine JUVÉDERM®

Safety

• With the exception of less pain and tenderness with JUVÉDERM® XC, CTRs were similar for all JUVÉDERM® formulations1

• There were no adverse events other than CTRs related to treatment1

Pivotal Study: Design1,2

• Multicenter, double-blind, randomized,within-subject study

• Assess the effectiveness and safety of JUVÉDERM®* compared with ZYPLAST® in the correction of moderate to severe NLFs

– JUVÉDERM® Ultra (24 HV), n = 146

– JUVÉDERM® Ultra Plus (30 HV), n = 146

• Each site had– Treating investigator (not masked)

– Independent expert reviewer (IER) (masked)

• All subjects masked

*Although 3 formulations of JUVÉDERM® were evaluated in the pivotal study, only 2 are currently available in the United States.1. Pinksy et al. Aesthetic Surg J. 2008; 2. Data on file, Allergan, Inc.

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Pivotal Study: Treatmentand Assessment1,2

• Treatment– Subjects randomly assigned to receive either JUVÉDERM® Ultra or

JUVÉDERM® Ultra Plus in 1 NLF

– All subjects received ZYPLAST® in opposite NLF

– Injections were provided to achieve optimal correction (1 or 2 touch-ups allowed within the first 4 weeks if necessary)

– Subjects followed for up to 24 weeks after last treatment

– At the conclusion of the randomized trial, an open-label, extendedfollow-up study included observations out to ~ 1.5 years after last treatment

• Assessment– Effectiveness: NLF severity rated by IER and subject on the

5-point NLF Severity Scale (NLFSS) (ie, none, mild, moderate, severe,or extreme)

– Safety/tolerability: Subjects recorded treatment-site reactions daily for14 days after initial treatment and each touch-up

IER = IER = Independent expert reviewer

15

1. Pinksy et al. Aesthetic Surg J. 2008; 2. Data on file, Allergan, Inc.

JUVÉDERM® Open-Label ExtendedFollow-up Study: Methods

• After completing 24 weeks of follow-up during the pivotal trial, subjects could return at their convenience for a complimentary repeat treatment with their preferred product1

• Subjects were assessed by the treating investigator when they returned forre-treatment (up to approximately 1.5 years after last treatment)2

• The number of subjects evaluated during the extended trial were1:– 116 of the 146 (79%) subjects in the JUVÉDERM® Ultra

injectable gel cohort

– 111 of the 146 (76%) subjects in the JUVÉDERM® Ultra Plusinjectable gel cohort

• Subjects returning for the follow-up study were representative of the pivotal trial subjects in terms of1:

– Baseline nasolabial fold (NLF) severity

– NLF severity at week 24

– Initial injection volume

16

1. Pinksy et al. Aesthetic Surg J. 2008; 2. Data on file, Allergan, Inc., Pinsky Final Report.

*Improvement of ≥ 1 in wrinkle assessment score (WAS) as assessed by treating investigator is defined as clinically significant.1. Pinksy et al. Aesthetic Surg J. 2008.

JUVÉDERM® Ultra PlusJUVÉDERM® Ultra

Majority of JUVÉDERM® Subjects Maintained a Clinically Significant* ImprovementLonger Than 9 Months¹

17

Sub

ject

s W

ith ≥

1-P

oin

t Im

pro

vem

ent

in W

AS

, %

JUVÉDERM® Ultra Plus in Severe NLFs: Physician Assessment¹

• Improvement of ≥ 1 point achieved by

– 96% of subjects at 24 weeks

– 81% of subjects at12 months or beyond

• Improvement of ≥ 2 points achieved by

– 67% of subjects at 24 weeks

– 38% of subjects at12 months or beyond

18

1. Adapted from Lupo et al. Plast Reconstr Surg. 2008.

Sub

ject

s W

ith C

linic

ally

Sig

nific

ant

Imp

rove

me

nt,

%

19

NLF Correction Over 17 Months: JUVÉDERM® Ultra Plus¹

1. Baumann et al. Dermatol Surg. 2007.

Baseline 2 weeks 8 weeks 24 weeks 17 months

JUVÉDERM® Is the Only HA Filler FDA Approved* to Last up to 1 YearWith Initial Treatment¹,2,†

• JUVÉDERM® Ultra and JUVÉDERM® Ultra Plus offer long-lasting clinical improvement for up to 1 year in NLFs

– Majority of subjects maintained a clinically significant improvement(≥ 1 point) over an extended period of time1,2

• JUVÉDERM® Ultra: 75% (> 9 months)

• JUVÉDERM® Ultra Plus: 78% (> 12 months)

• JUVÉDERM® Ultra Plus for severe NLFs: 81% ( 12 months)

• Repeat treatment required less than half of the original injection volume

• No treatment-related adverse events other than at the injection site

20

*In the United States, JUVÉDERM® injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds).†This includes all JUVEDERM injectable gel formulations. 1. Pinksy et al. Aesthetic Surg J. 2008; 2. Lupo et al. Plast Reconstr Surg. 2008.  

HA Resistance to Ovine Testicular Hyaluronidase (OTH) Methods¹

• Study purpose– To determine a dose-response relationship between commercially

available OTH and degradation of variousHA-based dermal filler products

•  Dose response – Test products incubated for 30 minutes with OTH concentrations

of 0, 5, 10, 20, and 40 U

• Time response (fixed 20-U enzyme concentration)– JUVÉDERM®: 30, 60, 120 minutes; 24 hours

• Outcome measure– Amount of soluble HA and molecular weight as determined by

SEC-MALS detector 

– An increase in total soluble HA indicates degradation of theHA network

21

SEC-MALS = size-exclusion chromatography coupled with a multiangle light scattering; soluble HA = uncross-linked HA or lightly cross-linked HA chains or fragments that are in soluble form.1. Jones et al. Dermatol Surg. In press.

JUVÉDERM® Has Greater Resistance to Degradation Than Restylane®, Yet Is Still MostlyDissolved by OTH Within 24 Hours¹,*,†

22

Units of Ovine Testicular Hyaluronidase (OTH)

% F

ree

HA

Afte

r 30

-Min

ute

Incu

batio

n

Free HA = uncross-linked HA and lightly cross-linked chains or fragments that are in soluble form.*In vitro.†Based on JUVÉDERM® Ultra Plus.1. Jones et al. Dermatol Surg. In press.

JUVÉDERM® Restylane®

**In the United States, JUVÉDERMn the United States, JUVÉDERM®® injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds). severe facial wrinkles and folds (such as nasolabial folds).

JUVÉDERM® Ultra XC

JUVÉDERM® Ultra Plus XC

23

Practical Uses for JUVÉDERM® XC

Product descriptionProduct description Syringe sizeSyringe size

24

JUVÉDERM® Product Availability

JUVÉDERM® Ultra XC 0.8 cc

JUVÉDERM® Ultra Plus XC 0.8 cc

JUVÉDERM® Ultra 0.8 cc

JUVÉDERM® Ultra Plus 0.8 cc

JUVÉDERM® Ultra Plus 0.4 cc

JUVÉDERM® Ultra 0.4 cc

The only HA filler FDA approved† to last up to1 year with initial treatment1,2,‡

The first and only smooth-consistency gel formulated with lidocaine

Provides a more comfortable patient experience1-3,*

25

JUVÉDERM® XC Sets the Standard

FDA = US Food and Drug Administration; HA = hyaluronic acid.*When compared to the nonlidocaine JUVÉDERM® formulations.†In the United States, JUVÉDERM® injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds). ‡This includes all JUVÉDERM® injectable gel formulations. 1. JUVÉDERM® Ultra XC Directions for Use; 2. JUVÉDERM® Ultra Plus Directions for Use; 3. Weinkle et al. J Cosmet Dermatol. 2009.

A Brief Description of Indications for Use, Contraindications, Warnings, Precautions, and Adverse Events for JUVÉDERM® Injectable Gel

26

Indication: In the United States, JUVÉDERM® injectable gel (including JUVÉDERM® Ultra, JUVÉDERM® Ultra Plus, JUVÉDERM® Ultra XC, and JUVÉDERM® Ultra Plus XC) is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds). Contraindications: JUVÉDERM® injectable gel should not be used in patients who have severe allergies marked by a history of anaphylaxis or history or presence of multiple severe allergies. JUVÉDERM® should not be used in patients with a history of allergies to Gram-positive bacterial proteins. JUVÉDERM® Ultra XC and JUVÉDERM® Ultra XC should not be used in patients with a history of allergies to lidocaine.

Warnings: JUVÉDERM® injectable gel should not be injected into blood vessels. If there is an active inflammatory process or infection at specific injection sites, treatment should be deferred until the underlying processis controlled.

A Brief Description of Indications for Use,Contraindications, Warnings, Precautions, and Adverse Events for JUVÉDERM® Injectable Gel (continued)

27

Precautions: The safety of JUVÉDERM® for use during pregnancy, in breastfeeding females, or in patients under 18 years has not been established. The safety and effectiveness of JUVÉDERM® injectable gel for the treatment of areas other than facial wrinkles and folds (such as lips) have not been established in controlled clinical studies. Patients who are using substances that can prolong bleeding, such as aspirin or ibuprofen, as with any injection, may experience increased bruising or bleeding at injection site. Patients should inform their physician before treatment if they are using these types of substances. As with all skin-injection procedures, there is a risk of infection. JUVÉDERM® should be used with caution in patients on immunosuppressive therapy, or therapy used to decrease the body’s immune response, as there may be an increased risk of infection. The safety of JUVÉDERM® in patients with a history of excessive scarring (eg, hypertrophic scarring and keloid formations) and pigmentation disorders has not been studied. If laser treatment, chemical peel, or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® injectable gel, or if JUVÉDERM® is administered before the skin has healed completely after such a procedure, there is a possible risk of an inflammatory reaction at the treatment site.

A Brief Description of Indications for Use,Contraindications, Warnings, Precautions, and Adverse Events for JUVÉDERM® Injectable Gel (continued)

28

Adverse events: The most commonly reported side effects are temporary injection-site redness, swelling, pain/tenderness, firmness, lumps/bumps, and bruising. MMost side effects are mild or moderate in nature, and their duration is short lasting (7 days).

Important: For full safety information, please visit www.juvederm.com or call Allergan Product Support at 1-877-345-5372.

CAUTION: Rx only.

For directions for use (DFU), please visit www.juvederm.com/dfu.

Bibliography

29

Baumann LS, Shamban AT, Lupo MP, et al; JUVÉDERM® vs. ZYPLAST® Nasolabial Fold Study Group. Comparison of smooth-gel hyaluronic acid dermal fillers with cross-linked bovine collagen: a multicenter, double-masked, randomized, within-subject study. Dermatol Surg. 2007;33(suppl 2):128S-135S.

Data on file, Allergan, Inc.

Data on file, Allergan, Inc.; JUVÉDERM® Technical File.

Data on file, Allergan, Inc., Pinsky Final Report.

Jackson D, Chen AH, Bennett CR. Identifying true lidocaine allergy. J Am Dent Assoc. 1994;125(10):1362-1366.

Jones B, Borrell M, Tezel A. Degradation by ovine testicular hyaluronidase (OTH): a comparison between a 24-mg/mL hyaluronic acid (HA) gel filler and 20- and 5.5-mg/mL HA gel fillers. Dermatol Surg. In press.

JUVÉDERM® Ultra XC Directions for Use.

JUVÉDERM® Ultra Plus XC Directions for Use.

Lupo MP, Smith SR, Thomas JA, Murphy DK, Beddingfield FC 3rd. Effectiveness of JUVÉDERM® Ultra Plus dermal filler in the treatment of severe nasolabial folds. Plast Reconstr Surg. 2008;121(1):289-297.

Pinsky MA, Thomas JA, Murphy DK, Walker PS; for JUVÉDERM® vs ZYPLAST® Nasolabial Fold Study Group. JUVÉDERM® injectable gel: A multicenter, double-blind, randomized study of safety and effectiveness. Aesthetic Surg J. 2008;28(1):17-23.

Weinkle SH, Bank DE, Boyd CM, Gold MH, Thomas JA, Murphy DK. A multi-center, double-blind, randomized controlled study of the safety and effectiveness of JUVÉDERM® injectable gel with and without lidocaine. J Cosmet Dermatol. 2009;8(3):205-210.

©2010 Allergan, Inc. ® and ™ marks owned by Allergan, Inc.

JUVÉDERM® mark owned by Allergan Industrie, SAS.EMLA is a registered trademark of Deutsche Bank AG, London Branch. Restylane is a registered trademarkof HA North American Sales AB.

www.juvederm.com/professional

APC25QE10 104622