Juvederm Family of Hyaluronic Acid Fillers
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Juvederm Family of Hyaluronic Acid Fillers

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Juvederm study/trial for wrinkle reduction in patients.

Juvederm study/trial for wrinkle reduction in patients.

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  • This presentation will cover an overview of the JUVÉDERM ® Family of Hyaluronic Acid Fillers We’ll review the unique manufacturing process including the impact of the new lidocaine formulation Then we’ll review the registration trial for the lidocaine product, JUVÉDERM ® XC, and briefly cover the pivotal extension trial that earned JUVÉDERM ® injectable gel the US Food and Drug Administration (FDA) approval for 1-year duration on the approved labeling, and following that we’ll review the severe folds study Finally, we’ll discuss which formulation is best to use in which areas of the face
  • JUVÉDERM ® XC sets the standard for hyaluronic acid (HA) fillers. Product characteristics include: Smooth flow—smooth-consistency gel with even and consistent extrusion force formulated with lidocaine Smooth comfort—provides a more comfortable patient experience vs the nonlidocaine JUVÉDERM ® formulation 1-3* Smooth outcomes—the only HA filler FDA approved † to last up to 1 year with initial treatment 1,2, ‡
  • This section of the presentation will highlight the physical and chemical properties of JUVÉDERM ® that contribute to its performance when used as a dermal filler Allergan’s proprietary HYLACROSS ™ technology differs from other techniques for the preparation of HA gels, by using a high degree of cross-linking and homogenization to achieve a robust yet smooth-consistency gel with even flow characteristics This combination of characteristics alleviates the need to include large amounts of free HA in the formulation, and delivers a smooth-consistency gel that allows the application of uniform extrusion force throughout the procedure to achieve smooth outcomes Homogenization creates random HA sizes and shapes that permit more effective filling of voids when the gel is blended resulting in a smoother consistency. Homogenization also helps maintain the gel’s cross-linking during the formulation process, preserving its cohesive qualities Ultimately, a unique 3D matrix is created that is strong and robust, yet still soft and smooth This slide has representations of the cross-linking for JUVÉDERM ® and a competitor. JUVÉDERM ® is cross-linked to a greater extent, thereby decreasing the likelihood of degradation
  • The slide is a conceptual illustration for explanation purposes only on how lidocaine is added as a dry substance to JUVÉDERM ® Compared with the formulation of JUVÉDERM ® , the formulation of JUVÉDERM ® XC injectable gel differs only in the addition of dry lidocaine The product incorporates the same HA, cross-linker, and HYLACROSS™ technology as JUVÉDERM ® There is no dilution of the final product or additional volume due to the addition of lidocaine Since lidocaine does not interfere with the cross-linking process, the final product has the same degree of cross-linking and retains all the favorable characteristics of JUVÉDERM ® And, because the lidocaine is preservative-free, the likelihood of an allergic reaction is low
  • Comparisons of JUVÉDERM ® XC formulations to their nonlidocaine-containing counterparts reveal no changes in pH, rheologic properties, or extrusion force, thus establishing their functional equivalence
  • This slide summarizes the key properties of the JUVÉDERM ® Family of Hyaluronic Acid Fillers JUVÉDERM ® Ultra and JUVÉDERM ® Ultra Plus differ from each other in their chemical and physical properties for versatility in clinical use You can see that the lidocaine formulation of each product is identical to its counterpart except for the presence of lidocaine
  • We will now discuss the JUVÉDERM ® Family of Hyaluronic Acid Fillers and its clinical evidence. Its value in clinical practice will also be discussed The purpose of this pivotal trial was to demonstrate the reduction in procedural pain and evaluate the safety of JUVÉDERM ® XC compared with JUVÉDERM ® formulations that do not contain lidocaine In this split-face study, 72 subjects at 4 study centers received JUVÉDERM ® Ultra XC (n = 36) or JUVÉDERM ® Ultra Plus XC (n = 36) in 1 NLF, and JUVÉDERM ® Ultra or JUVÉDERM ® Ultra Plus without lidocaine in the opposite NLF No dental block was used; ice and/or EMLA ® were permitted The investigator selected the filler and volume that were appropriate for each subject Subjects were treated with up to 1.6 mL (or 2 syringes) per NLF
  • After informed consent, baseline NLF severity was assessed using the 5-point NLF Severity Scale (NLFSS) After both sides were treated, subjects reported their pain level, comparative procedural pain between the right and left NLF, and assessed NFL severity A telephone or e-mail follow-up visit was conducted by the investigator on the second day following treatment to assess common treatment-site responses (CTRs) Subjects entered CTRs through an interactive voice response system (IVRS). If there was no corresponding selection in the IVRS for a given treatment response, the subjects reported those occurrences directly to the investigator At the final study visit, the investigators assessed NLF severity
  • The primary measure was procedural pain that was graded on a 10-point categorical scale Secondary measures included a comparison of the right and left side treatment-related pain obtained immediately after both sides were treated NLF severity was measured prior to treatment using a 5-point scale (NLF Severity Scale [NLFSS]) and again at the final study visit. The improvement in NLF severity was calculated from these measures
  • Subjects accessed an IVRS system to record the absence, presence, severity, and location of treatment-site responses If a specific CTR was not available as a selection on the IVRS, subjects were instructed to report those occurrences directly to the investigator
  • For both formulations of JUVÉDERM ® XC, more than 90% of subjects reported less pain than on the side treated with JUVÉDERM ® without lidocaine 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 lidocaine Procedural pain scores were significantly lower for both JUVÉDERM ® Ultra XC and JUVÉDERM ® Ultra Plus XC Reduction in procedural pain scores between JUVEDERM ® with and without lidocaine was significant regardless of needle type, injection volume, use of topical anesthesia, and across investigators.
  • The treatment responses for all JUVÉDERM ® formulations were mild to moderate in severity, were typical of those observed with the use of HA fillers, and were mostly procedure-related Pain and tenderness were significantly reduced for JUVÉDERM ® XC formulations; no subject reported severe pain for JUVÉDERM ® XC Common treatment-site responses that extended beyond 14 days were classified as adverse events (AEs). There were few responses classified as AEs and there were no significant differences in AEs between formulations The incidence of AEs for JUVÉDERM ® XC and JUVÉDERM ® formulations were similar Most patients who have allergic reactions to lidocaine are sensitive to the preservatives rather than the lidocaine itself
  • The key top-line results to take from this trial are that: Treatment with JUVÉDERM ® XC formulations elicited fewer reports of pain than the corresponding nonlidocaine formulations in more than 90% of subjects Regardless of the treatment-related factors, physician- and subject-reported pain and tenderness were significantly lower for the lidocaine-based formulations of JUVÉDERM ® NLF severity was significantly improved with all JUVÉDERM ® injectable gel formulations There were few CTRs for any JUVÉDERM ® formulation Those that did occur were mild to moderate in severity and mostly procedure-related There were no significant differences in CTRs among the JUVÉDERM ® formulations other than pain
  • A large multicenter, double-blind, randomized pivotal trial included 3 formulations of JUVÉDERM ® ; only 2 are currently available in the United States. This study formed the basis for the June 2006 FDA approval of the JUVÉDERM ® Family of Hyaluronic Acid Fillers In the pivotal trial, JUVÉDERM ® dermal filler was compared with ZYPLAST ® bovine collagen in the treatment of NLFs. Collagens have been the standard comparators Each study site had 2 investigators who were considered experienced physician specialists in cosmetic dermatology or plastic surgery—one served as the treating investigator and performed the injections. The other, an independent expert reviewer (IER), served as a masked investigator and evaluated the effects of treatment. The subjects also were masked
  • All patients were randomized to receive JUVÉDERM ® Ultra or JUVÉDERM ® Ultra Plus formulations in 1 NLF. They received ZYPLAST ® in the other NLF Each NLF was treated to achieve full (100%) correction, without overcorrection. To make sure all treated subjects reached optimal correction, up to 2 touch-ups were allowed within 4 weeks after the initial treatment. The patients were then followed for 24 weeks after the last treatment, including any touch-ups At the conclusion of the randomized trial, an open-label, extended follow-up study included observations out to approximately 1.5 years after the last treatment to determine long-term safety and effectiveness Effectiveness of treatment was assessed at least once per month for the 6-month period of the randomized trial by the blinded evaluating investigator as well as by patients, using the 5-point NFL Severity Scale (NLFSS) with ratings ranging from 0 for none to 4 for extreme To evaluate safety and tolerability, subjects were instructed to keep a diary and record any treatment-site reactions for 2 weeks after each treatment
  • We will now discuss the JUVÉDERM ® open-label extended follow-up study After completing 24 weeks of the pivotal trial, subjects were offered a complimentary treatment with their preferred product at their convenience 1 Upon their return, they were first assessed by the treating investigator. They were then re-treated, up to approximately 1.5 years after their last treatment 2 More than three-quarters of JUVÉDERM ® subjects were evaluated during the extended trial 1 These subjects were representative of the pivotal trial subjects in terms of baseline NLF severity, NLF severity at week 24, and initial injection volume 1
  • The 2 graphs on this slide show the percentage of subjects with clinically significant improvement following optimal correction with JUVÉDERM ® Ultra and JUVÉDERM ® Ultra Plus 1 Note that those beyond 12 months are a subset of the beyond-9-month group 1 A total of 75% of the subjects treated with JUVÉDERM ® Ultra maintained improvement beyond 9 months; 68% still had clinically significant improvement beyond 1 year 1 Beyond 12 months, 78% of JUVÉDERM ® Ultra Plus injectable gel subjects still demonstrated at least a 1-point improvement in NLF severity 1 Through the extended study, both JUVÉDERM ® formulations have proven to be highly effective, with visible improvement over an extended period of time (more than 9 months) 1
  • This analysis evaluated the performance of JUVÉDERM ® Ultra Plus in sustaining correction in the subset of 87 pivotal trial subjects with severe NLFs. (This corresponds with a grade 3 on the NLFSS) 1 This graph compares the proportion of subjects with clinically significant improvement in NLF severity at 6 months and 1 year or more 1 Clinical significance was previously defined as a 1-point or greater reduction in NLF severity. The first 2 bars indicate that a substantial proportion of subjects, more than 80%, still experienced clinical benefit even after 1 year. These values were observed before the subjects had any repeat treatments 1 Let’s take a look at the second set of bars. Although it was not required by the study, we calculated the proportion of subjects exhibiting a 2-point or greater improvement in NLF severity. The proportion still experiencing improvement beyond 12 months was a little over one-third 1
  • This JUVÉDERM ® Ultra Plus subject presented approximately 17 months after last treatment¹ The duration of JUVÉDERM ® results, 17 months after initial treatment, speaks for itself¹ The results may not be typical
  • In summary, the JUVÉDERM ® Family of Hyaluronic Acid Fillers offers long-lasting clinical improvement of 1 point or more for up to 1 year 1 The majority of subjects in both arms maintained a clinically significant improvement JUVÉDERM ® Ultra for > 9 months, 75%¹ JUVÉDERM ® Ultra Plus for > 12 months, 78%¹ JUVÉDERM ® Ultra Plus for severe NLFs, (> 12 months) 81% 2 Repeat treatment required only about half the volume used for the initial treatment¹ There were no treatment-related adverse events other than injection-site reactions¹ All these findings confirm that the scientists at Allergan, Inc., achieved the clinical profile they targeted when designing these new-generation HA fillers
  • The purpose of this study was to assess the dose response of various HA fillers to commercially available ovine testicular hyaluronidase (OTH) Based on the varied degree of enzymatic degradation of commercially available fillers to hyaluronidase that has been reported in the literature, and due to the different HA concentration of the fillers studied in this series of tests, it was anticipated that the degradation patterns of the fillers would differ. Therefore, variable methods were used 1 : Variable doses of OTH (0 U to 40 U) for a fixed period of time (30 minutes) Incubation of JUVÉDERM ® with 20 U OTH for 30, 60, and 120 minutes; and 24 hours The amount of soluble HA and molecular weight of the test products was determined by size-exclusion chromatography coupled with a multiangle light scattering detector. In this study, the definition of soluble HA includes the uncross-linked HA added during its manufacturing process, as well as lightly cross-linked chains and gel fragments generated as degradation products of the gel network. An increase in total soluble HA will therefore indicate degradation of the HA network
  • JUVÉDERM ® showed greater resistance against in vitro enzymatic degradation by OTH compared with Restylane ®1 After incubation with 20 U of OTH for 30 minutes, percentage soluble “free” HA was 18.5% and 87.9% for JUVÉDERM ® and Restylane ® , respectively The percent soluble HA after incubating with 40 U of OTH for 30 minutes was 27.6% and 90.4% for JUVÉDERM ® injectable gel and Restylane ® , respectively   After 24 hours of incubation with 40 U of OTH, the percent soluble HA of JUVÉDERM ® was 88.4%
  • Next, let’s discuss the utility and versatility of the JUVÉDERM ® Family of Hyaluronic Acid Fillers in clinical practice The JUVÉDERM ® Ultra Plus XC side of the model’s face depicts wrinkles and folds typically injected with this formulation These include NLFs, oral commissures, and marionette lines Now let’s take a look at the JUVÉDERM ® Ultra XC side of the model’s face The typical areas for JUVÉDERM ® Ultra and JUVÉDERM ® Ultra XC use include vertical lip lines, oral commissures, NLFs, marionette lines, and chin wrinkles (Physicians, please add your own experience for optimal on-label uses) We have seen that it is a combination of chemical and physical attributes that allows for JUVÉDERM ® and JUVÉDERM ® XC to each play an important role in facial aesthetics. The choice of which filler to use should be decided based on subject desire and need as well as injector’s experience and ease of use. However, together, both products provide the versatility injectors require in their filler armamentarium
  • JUVÉDERM ® is now available in both lidocaine and nonlidocaine formulations for your convenience This table highlights all of the JUVÉDERM ® products and the syringe sizes available for each product
  • JUVÉDERM ® XC sets the standard for hyaluronic acid (HA) fillers. Product characteristics include: Smooth flow—smooth-consistency gel with even and consistent extrusion force formulated with lidocaine Smooth comfort—provides a more comfortable patient experience vs the nonlidocaine JUVÉDERM ® formulation 1-3* Smooth outcomes—the only HA filler FDA approved † to last up to 1 year with initial treatment 1,2, ‡

Juvederm Family of Hyaluronic Acid Fillers Juvederm Family of Hyaluronic Acid Fillers Presentation Transcript

  • JUVÉDERM®Family of Hyaluronic Acid Fillers
  • 2 JUVÉDERM® XC Sets the Standard The first and only smooth-consistency gel formulated with lidocaine Provides a more comfortable patient experience1-3,* The only HA filler FDA approved† to last up to 1 year with initial treatment1,2,‡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 facialwrinkles 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.
  • 3 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 JUVÉDERM® Competitive HA fillers More cross-linked Smooth consistency Less cross-linked Granular consistencyThe significance of the difference has not been established in controlled clinical studies.1. Data on file, Allergan, Inc.; JUVÉDERM® Technical File.
  • 4 Adding Lidocaine as a Dry Substance Ensures the Same Chemical and Physical Characteristics as JUVÉDERM® Injectable Gel Without Lidocaine • Addition of lidocaine has no effect on1,2: – HA concentration or volume – Product viscosity or extrusion force – HA degradation – pH level1. Weinkle et al. J Cosmet Dermatol. 2009; 2. Data on file, Allergan, Inc.
  • 5 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 HA cross-linking1,2 • Lidocaine is rapidly released from the gel and metabolized after the dermal filler is injected1,2 JUVÉDERM® Injectable Gel Chemical/Physical Test With and Without Lidocaine Susceptibility to degradation • Enzymatic Equivalent • Free radical Rheologic properties Equivalent pH Equivalent Extrusion force Equivalent1. Weinkle et al. J Cosmet Dermatol. 2009; 2. Data on file, Allergan, Inc.
  • 6 Summary of JUVÉDERM Physical ® and Chemical Properties¹ JUVÉDERM ® JUVÉDERM ® JUVÉDERM ® JUVÉDERM ® Ultra Ultra Ultra XC Ultra Plus Plus XC Lidocaine concentration NA 0.3% NA 0.3% Total HA concentration 24 mg/mL 24 mg/mL 24 mg/mL 24 mg/mL Percentage ~10% ~10% ~10% ~10% uncross-linked HAa Degree of cross-linking ~6% ~6% ~8% ~8% Smooth Smooth Smooth Smooth Formulation cohesive gel cohesive gel cohesive gel cohesive gel Needle 30 G 30 G 27 G 27 Ga Uncrosslinked 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.
  • 7 JUVÉDERM XC Pivotal Study: ® Comparison of Effectiveness and Safety With JUVÉDERM®¹ 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 NLFNLF = nasolabial fold.1. Weinkle et al. J Cosmet Dermatol. 2009.
  • 8 JUVÉDERM XC Study Flow ® and Assessments¹ Day 2 Day 14 Day 0 (Phone/e-mail) (Office visit) JUVÉDERM® treatment Investigator Baseline Investigator Assessment: Investigator Day 14 Assessment: Common treatment-site Assessment: NLF Severity Scale (NLFSS) responses (CTRs) NLF Severity Scale (NLFSS) Treatment: Investigator Assessment: Randomization, CTRs injection volume, technique Subject Assessment: Subject Assessment: Procedural pain score NLF Severity Scale (NLFSS) Comparative procedural pain score NLF Severity Scale (NLFSS) Subject Diary for CTRs1. Weinkle et al. J Cosmet Dermatol. 2009.
  • 9 JUVÉDERM XC Subject and Investigator ® Effectiveness Assessments¹ Primary: Procedural Pain Subjects rated pain during injection; 0–10 scale within 30 minutes after both sides were treated 0 10 1 2 3 4 5 6 7 8 9 Worst No pain pain imaginable 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 -2 -1 0 1 2 Right slightly more Left slightly more Right more painful painful No difference painful Left more painful Secondary: NLF Severity Scale (NLFSS) Investigators and subjects rated NLF severity; 5-point scale at pretreatment and day 14 0 1 2 3 4 None Mild Moderate Severe Extreme1.Weinkle et al. J Cosmet Dermatol. 2009.
  • 10 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 CTRsCTR = common treatment-site response1.Weinkle et al. J Cosmet Dermatol. 2009; 2. Data on file, Allergan, Inc.
  • 11 JUVÉDERM XC Provides a More ® Comfortable Patient Experience 1-3 More Than 90% of the Subjects JUVÉDERM® XC Provides Significant Reported Less Treatment Pain Reduction in Pain Compared With With JUVÉDERM® XC1-3,* JUVÉDERM® Without Lidocaine1-3,* (N = 72) Less painful 63% 64% reduction 29% Slightly less painful 4% With Lidocaine Without Lidocaine More painful 3% Slightly more painful P < .001 (N=72)*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.
  • 12 With the Exception of Pain and Tenderness, CTRs Were Similar for All JUVÉDERM® Formulations 1-3 • 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 powder41.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 .
  • 13 Summary of JUVÉDERM XC ® Registration Trial 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*When compared to the nonlidocaine formulations.1. Weinkle SM et al. J Cosmet Dermatol. 2009.
  • 14 Pivotal Study: Design 1,2 • 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.
  • 15 Pivotal Study: Treatment and Assessment 1,2 • 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, extended follow-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 for 14 days after initial treatment and each touch-upIER = Independent expert reviewer 1. Pinksy et al. Aesthetic Surg J. 2008; 2. Data on file, Allergan, Inc.
  • 16 JUVÉDERM Open-Label Extended ® Follow-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 for re-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 Plus injectable 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 volume1. Pinksy et al. Aesthetic Surg J. 2008; 2. Data on file, Allergan, Inc., Pinsky Final Report.
  • 17 Majority of JUVÉDERM Subjects Maintained a ® Clinically Significant* Improvement Longer Than 9 Months¹ JUVÉDERM® Ultra JUVÉDERM® Ultra Plus Improvement in WAS, % Subjects With ≥ 1-Point*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.
  • 18 JUVÉDERM Ultra Plus in Severe NLFs: ® Physician Assessment¹ • Improvement of ≥ 1 point achieved by Subjects With Clinically Significant – 96% of subjects at 24 weeks – 81% of subjects at Improvement, % 12 months or beyond • Improvement of ≥ 2 points achieved by – 67% of subjects at 24 weeks – 38% of subjects at 12 months or beyond1. Adapted from Lupo et al. Plast Reconstr Surg. 2008.
  • 19 NLF Correction Over 17 Months: JUVÉDERM® Ultra Plus¹ Baseline 2 weeks 8 weeks 24 weeks 17 months1. Baumann et al. Dermatol Surg. 2007.
  • 20 JUVÉDERM Is the Only HA Filler FDA ® Approved to Last up to 1 Year* With 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*In the United States, JUVÉDERM® injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinklesand 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.
  • 21 HA Resistance to Ovine Testicular Hyaluronidase (OTH) Methods¹ • Study purpose – To determine a dose-response relationship between commercially available OTH and degradation of various HA-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 the HA networkSEC-MALS = size-exclusion chromatography coupled with a multiangle light scattering; soluble HA = uncross-linked HA or lightly cross-linkedHA chains or fragments that are in soluble form.1. Jones et al. Dermatol Surg. In press.
  • 22 JUVÉDERM® Has Greater Resistance to Degradation Than Restylane®, Yet Is Still Mostly ,*,† Dissolved by OTH Within 24 Hours¹ Units of Ovine Testicular Hyaluronidase (OTH) After 30-Minute Incubation % Free HA JUVÉDERM® Restylane®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.
  • 23 Practical Uses for JUVÉDERM® XC JUVÉDERM® JUVÉDERM® Ultra XC Ultra Plus XC*In the United States, JUVÉDERM® injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to nsevere facial wrinkles and folds (such as nasolabial folds).
  • 24JUVÉDERM® Product Availability Product description Syringe size 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
  • 25 JUVÉDERM® XC Sets the Standard The first and only smooth-consistency gel formulated with lidocaine Provides a more comfortable patient experience1-3,* The only HA filler FDA approved† to last up to 1 year with initial treatment1,2,‡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 facialwrinkles 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.
  • 26A Brief Description of Indications for Use,Contraindications, Warnings, Precautions, and AdverseEvents for JUVÉDERM® Injectable Gel 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 process is controlled.
  • 27A Brief Description of Indications for Use,Contraindications, Warnings, Precautions, and Adverse Eventsfor JUVÉDERM® Injectable Gel (continued) 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.
  • 28A Brief Description of Indications for Use,Contraindications, Warnings, Precautions, and AdverseEvents for JUVÉDERM® Injectable Gel (continued) Adverse events: The most commonly reported side effects are temporary injection-site redness, swelling, pain/tenderness, firmness, lumps/bumps, and bruising. Most 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.
  • 29BibliographyBaumann LS, Shamban AT, Lupo MP, et al; JUVÉDERM® vs. ZYPLAST® Nasolabial Fold Study Group. Comparison of smooth-gelhyaluronic 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 treatmentof 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® injectablegel: 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 thesafety 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 trademark of HA North American Sales AB. www.juvederm.com/professional APC25QE10 104622