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`Meeting of the
`General and Plastic Surgery Devices Panel
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`FDA Advisory Committee Briefing Document
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`May 2, 2013
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`JUVÉDERM VOLUMA™ XC
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`PMA P110033
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`Briefing Book
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`Page 1 of 111
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`Exhibit 1103
`Prollenium v. Allergan
`IPR2019-01505 et al.
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`1. TABLE OF CONTENTS
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`JUVÉDERM VOLUMA™ XC
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`1.
`2.
`3.
`4.
`5.
`6.
`7.
`8.
`9.
`10.
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`TABLE OF CONTENTS ............................................................................................ 3 
`LIST OF FIGURES .................................................................................................... 5 
`LIST OF TABLES ....................................................................................................... 7 
`TERMS AND ABBREVIATIONS ............................................................................. 9 
`EXECUTIVE SUMMARY ........................................................................................ 11 
`CLINICAL NEED FOR MID-FACIAL VOLUMIZING ...................................... 15 
`DERMAL FILLER REGULATORY HISTORY ................................................... 19 
`DEVICE DESCRIPTION ........................................................................................ 23 
`PRE-CLINICAL TESTING ..................................................................................... 27 
`VOLUMA-002 CLINICAL STUDY DESIGN ....................................................... 31 
`10.1  Overview of Pivotal Study Design ................................................................... 32 
`10.1.1  Enrollment .......................................................................................... 32 
`10.1.2  Treatment ............................................................................................ 33 
`10.1.3  Follow-up ............................................................................................ 34 
`10.1.4  Discussion of Study Design ................................................................ 36 
`10.1.5  Selection of Study Population ............................................................ 38 
`10.2  Effectiveness Measures and Analyses .............................................................. 39 
`10.2.1  Primary Effectiveness Measure and Analysis ..................................... 39 
`10.2.2  Secondary Effectiveness Measurements and Analyses ...................... 41 
`10.2.3  Additional Effectiveness Measurements and Analyses ...................... 42 
`10.3  Safety Measurements ....................................................................................... 45 
`10.4  Analysis Population .......................................................................................... 46 
`10.4.1  Main Analyses .................................................................................... 46 
`10.4.2  Subgroup Analyses ............................................................................. 47 
`10.5  Appropriateness of Measurements ................................................................... 49 
`10.5.1  MFVDS ............................................................................................... 49 
`10.5.2  GAIS, NLFS, and OAFM ................................................................... 51 
`10.5.3  Patient Reported Outcomes ................................................................ 51 
`10.5.4  3D Imagery Volume Calculations ....................................................... 52 
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`VOLUMA-002 CLINICAL STUDY RESULTS ..................................................... 53 
`11.1  Subject Disposition ........................................................................................... 53 
`11.1.1  Primary Safety and Effectiveness Period ............................................ 53 
`11.1.2  Extended Follow-up Period ................................................................ 55 
`11.1.3  Repeat Treatment and Follow-up ........................................................ 55 
`11.2  Subject and Treatment Characteristics ............................................................. 55 
`11.2.1  Subject Demographics ........................................................................ 55 
`11.2.2  Treatment Administration ................................................................... 57 
`11.3  Protocol Deviations .......................................................................................... 60 
`11.4  Effectiveness Results ........................................................................................ 61 
`11.4.1  Primary Effectiveness Results ............................................................ 61 
`11.4.2  Secondary Effectiveness Results ........................................................ 65 
`11.4.3  Effectiveness Beyond Month 6 using MFVDS and GAIS ................. 66 
`11.4.4  Additional Effectiveness ..................................................................... 68 
`11.4.5  Subject Self-Assessments ................................................................... 69 
`11.4.6  Subgroup Analysis .............................................................................. 71 
`11.5  Duration of Effect ............................................................................................. 74 
`11.6  Safety Results ................................................................................................... 76 
`11.6.1  Common Treatment Responses .......................................................... 76 
`11.6.2  Adverse Events ................................................................................... 79 
`11.6.3  Subgroup Analyses of Device-Related Adverse Events ..................... 84 
`11.6.4  Common Treatment Site Responses and Adverse Events After Repeat
`Treatment .................................................................................................. 85 
`11.7  Histopathology Results ..................................................................................... 86 
`POST-APPROVAL PLANS...................................................................................... 89 
`PRODUCT EXPERIENCE WITH VOLUMA™ .................................................... 91 
`13.1  Post-Approval Studies World-Wide ................................................................. 91 
`13.2  Summary of Relevant Literature ...................................................................... 91 
`13.3  Post-Market Surveillance Data on VOLUMA™ XC ........................................ 94 
`BENEFIT AND RISK ASSESSMENT .................................................................... 97 
`CONCLUSION ....................................................................................................... 103 
`REFERENCES ........................................................................................................ 105 
`APPENDICES .......................................................................................................... 111 
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`11.
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`17.
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`2. LIST OF FIGURES
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`Figure 1. VOLUMA-002 Clinical Study Design ................................................................... 13 
`Figure 2. Zygomaticomalar Complex .................................................................................... 15 
`Figure 3. Hyaluronic Acid...................................................................................................... 23 
`Figure 4. Chemical Structure of BDDE ................................................................................. 24 
`Figure 5. VOLUMA-002 Clinical Study Design ................................................................... 31 
`Figure 6. Mid-Face Regions Treated ..................................................................................... 34 
`Figure 7. Mid-Face Volume Deficit Scale Example Photos .................................................. 40 
`Figure 8. Subject Diary .......................................................................................................... 46 
`Figure 9. Subject Disposition, mITT, and Month 6 Evaluable Populations .......................... 54 
`Figure 10. Primary Endpoint Analysis .................................................................................. 62 
`Figure 11. GAIS Responder Rate at Month 6 ........................................................................ 65 
`Figure 12. MFVDS Responder Rates by Mid-Face Region at Month 6 ................................ 66 
`Figure 13. 3D Imaging Calculation of Mid-Face ................................................................... 68 
`Figure 14. Subject GAIS Assessment .................................................................................... 69 
`Figure 15. Subject Satisfaction with Mid-Face Regions ....................................................... 70 
`Figure 16. Satisfaction with Facial Appearance Since Baseline ............................................ 70 
`Figure 17. Duration of Volumizing Effect ............................................................................. 75 
`Figure 18. Duration of Volumizing Effect by Volume Injection ............................................ 76 
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`3. LIST OF TABLES
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`JUVÉDERM VOLUMA™ XC
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`Table 1. Comparison of VOLUMA™ XC to the FDA-approved family of JUVÉDERM®
`formulations .............................................................................................. 26 
`Table 2. Summary of Biocompatibility Testing ..................................................................... 28 
`Table 3. Follow-Up Schedule ................................................................................................ 35 
`Table 4. Fitzpatrick Skin Phototype Scale ............................................................................. 37 
`Table 5. Mid-Face Volume Deficit Scale Wording ................................................................ 40 
`Table 6. 5-Point Global Aesthetic Improvement Scale .......................................................... 41 
`Table 7. 5-Point NLF Severity Scale ..................................................................................... 42 
`Table 8. Endpoints Evaluated ................................................................................................ 44 
`Table 9. MFVDS Scale Validation: Inter-Rater Agreement .................................................. 50 
`Table 10. Subject Demographics: mITT ................................................................................ 56 
`Table 11. Subject MFVDS Baseline Characteristics .............................................................. 57 
`Table 12. Types of Anesthesia Used During Initial Treatment .............................................. 57 
`Table 13. Treatment Sites ....................................................................................................... 58 
`Table 14. Volume Injected for Treated mITT Subjects .......................................................... 58 
`Table 15. Major Protocol Deviations (Treatment and Control Subjects) ............................... 60 
`Table 16. Primary Effectiveness Analysis (mITT Population) .............................................. 62 
`Table 17. Month 6 MFVDS Responder Rates (PP Population) ............................................. 63 
`Table 18. Difference in Treatment and Control Group MFVDS Responder Rates at Month 6
`with Data Imputation Scenarios ................................................................ 65 
`Table 19. MFVDS Responder Rates through Month 24 ........................................................ 66 
`Table 20. GAIS Responder Rates through Month 24 ............................................................ 67 
`Table 21. Subgroup Effectiveness Analyses for Treatment Group ........................................ 72 
`Table 22. Month 6 Multivariate Subgroup Effectiveness Analyses for Treatment Group ..... 74 
`Table 23. Common Treatment Site Responses by Maximum Severity ................................. 77 
`Table 24. Common Treatment Site Responses by Maximum Duration ................................. 78 
`Table 25. Common Treatment Site Responses with JUVÉDERM® Ultra Plus vs.
`VOLUMA™ XC ........................................................................................ 79 
`Table 26. Serious Adverse Events Unrelated to the Device or Treatment ............................. 80 
`Table 27. Device-Related Adverse Events ............................................................................. 82 
`Table 28. Device-related Adverse Events Reported as Moderate and Requiring Treatment . 83 
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`Table 29. Serious Adverse Events Related to the Device or Treatment ................................. 84 
`Table 30. Multivariate Analysis of Device-Related Adverse Events ..................................... 85 
`Table 31. Common Treatment Site Responses after Repeat Treatment by Maximum Severity
`................................................................................................................... 85 
`Table 32. Common Treatment Site Responses after Repeat Treatment by Duration ............. 86 
`Table 33. Summary of Juvéderm VOLUMA™ Use in Published Literature ........................ 93 
`Table 34. Worldwide Reported Medical Events for VOLUMA™ and VOLUMA™ XC ..... 95 
`Table 35. Worldwide Reported Technical Events for VOLUMA™ and VOLUMA™ XC .. 95 
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`4. TERMS AND ABBREVIATIONS
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`Term/Abbreviation
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`Definition
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`JUVÉDERM VOLUMA™ XC
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`AE
`BDDE
`CFR
`COC
`CRF
`CTR
`DCF
`EI
`FAE
`FLO
`GAIS
`GCP
`HA
`IDE
`Initial Treatment
`Initial Treatment Period
`IRB
`LAF
`LAFM
`MFVDS
`mITT
`NLF
`NLFS
`OAFM
`PP
`PRO
`Repeat Treatment
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`SAE
`SPA
`TI
`Touch-up Treatment
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`Adverse event
`1,4-butanediol diglycidyl ether
`Code of Federal Regulations
`Cyclicolefin co-polymer
`Case report form
`Common treatment site response
`Data clarification form
`Evaluating Investigator
`Facial Appearance Evaluation
`Facial Lines Outcome
`Global Aesthetic Improvement Scale
`Good Clinical Practice
`Hyaluronic acid
`Investigational Device Exemption
`First treatment session
`Initial Treatment + Touch-up Treatment, separated by approximately 30 days
`Institutional Review Board
`Look and Feel
`Look and Feel of Mid-Face
`Mid-Face Volume Deficit Scale
`Modified intent-to-treat
`Nasolabial fold
`NLF Severity Scale
`Other Aesthetic Features of the Mid-Face
`Per protocol
`Patient reported outcomes
`Optional, complimentary treatment offered 12-24 months after initial treatment
`period
`Serious adverse event
`Self-Perception of Age
`Treating Investigator
`Treatment to reach optimal correction, if necessary, performed within the
`initial treatment period
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`5. EXECUTIVE SUMMARY
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`JUVÉDERM VOLUMA™ XC
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`This briefing document summarizes the data from the Allergan Premarket Approval (PMA)
`application for JUVÉDERM VOLUMA™ XC injectable gel, hereafter referred to as
`VOLUMA™ XC, for deep (subcutaneous and/or supraperiosteal) injection for cheek
`augmentation to correct age-related volume deficit in the mid-face. This PMA is currently
`under review by the Office of Device Evaluation (ODE) within the Center for Devices and
`Radiological Health (CDRH) of the US Food and Drug Administration (FDA).
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`One of the effects of aging is the gradual formation of wrinkles, folds, and lines, and loss of
`volume loss, resulting in dramatic changes to the overall contour of the face. Mid-face
`volume deficit is one of the changes that takes place in varying degrees as people age, with
`lost soft tissue revealing the bony structural elements of the face. The appearance and
`condition of facial skin may communicate not only age, but also vitality.1 A youthful
`appearance has been associated with increased self-esteem and improved social relations.2
`Thus, patients and physicians seek safe and effective treatment options which are specific for
`the facial region being addressed to help them fulfill their individual treatment goals.
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`The clinical need to replace lost facial volume is reflected in FDA approval of the first
`dermal filler device over 30 years ago. Since that time, multiple dermal fillers have been
`approved for injection into the mid to deep dermis for the correction of moderate to severe
`facial wrinkles and folds (such as nasolabial folds). Due to its highly favorable safety and
`effectiveness profile, the majority of these approvals have been for hyaluronic acid fillers.
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`Recently, a more comprehensive understanding of the effects of the aging process on tissue
`volumes has led to increased focus on volume restoration to correct tissue sagging and
`address fat loss in the face. Addressing overall volume loss has begun to take the place of
`merely filling winkles and folds. This paradigm shift in the approach to facial rejuvenation
`prompted the development and evaluation of VOLUMA™ XC for the correction of age-
`related mid-face volume deficit. The proposed indication statement for VOLUMA™ XC is as
`follows:
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`JUVÉDERM VOLUMA™ XC is indicated for deep (subcutaneous and/or
`supraperiosteal) injection for cheek augmentation to correct age-related volume
`deficit in the mid-face.
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`VOLUMA™ XC is a transparent, biodegradable, sterile, crosslinked, hyaluronic acid
`hydrogel formulated to neutral pH in a physiological buffer. Similar to members of the
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`JUVÉDERM VOLUMA™ XC
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`JUVÉDERM® family, approved and marketed in the US and worldwide for correction of
`moderate to severe wrinkles, VOLUMA™ XC is composed of hyaluronic acid biosynthesized
`by Streptococcus equi, chemically crosslinked with 1,4 butanediol diglycidyl ether, includes
`0.3% lidocaine to reduce pain upon injection, and is provided in a 1 mL plastic syringe.
`However, VOLUMA™ XC differs from the members of the JUVÉDERM® family in strategic
`physical and chemical characteristics that make it better suited for the prospective indication:
`restoration of age-related mid-face volume deficit.
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`In preclinical testing, the biocompatibility of VOLUMA™ XC was evaluated in accordance
`with the International Standards Organization (ISO) 10993. The results demonstrated that
`VOLUMA™ XC is non-cytotoxic, a non-irritant, non-toxic, non-sensitizing, non-genotoxic,
`non-pyrogenic, and well tolerated.
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`Based on these positive biocompatibility results and an extensive data package presented to
`countries outside the US, the VOLUMA™ formulation without lidocaine was first approved
`for use in Europe starting in 2005. World-wide approval of VOLUMA™ XC (identical in
`formulation, but with lidocaine incorporated) began in 2009. As of December 31, 2012,
`VOLUMA™ and VOLUMA™ XC have been approved in over 60 countries including
`Canada and countries in the EU, and more than 520,000 syringes of VOLUMA™ and
`VOLUMA™ XC have been sold. Post-market surveillance data has revealed a similar safety
`profile to other marketed hyaluronic acid based dermal fillers.
`
` A
`
` clinical trial of VOLUMA™ XC (protocol VOLUMA-002) has been conducted in the US
`and Canada to support US FDA approval. The primary objective of VOLUMA-002 was to
`evaluate the safety and effectiveness of VOLUMA™ XC for age-related cheek augmentation
`in the mid-face. Subjects with moderate to severe age-related mid-face volume deficit were
`followed for up to 24 months following treatment with VOLUMA™ XC. Under the study
`design, subjects were assigned to either receive treatment with VOLUMA™ XC, or to
`participate in a “no-treatment” control group, where treatment would be delayed until after
`the primary 6-month follow-up period. At the end of the 12-24 month follow-up period, an
`optional repeat treatment with an additional 12 months scheduled follow-up was offered to
`all subjects (Figure 1).
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`Figure 1. VOLUMA-002 Clinical Study Design
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`JUVÉDERM VOLUMA™ XC
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`In this study, a responder was defined as a subject with a ≥1 grade improvement on the
`validated photometric Mid-Face Volume Deficit Scale (MFVDS) compared to baseline.
`VOLUMA™ XC was determined to be clinically effective if the treatment group’s Month 6
`responder rate was:
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`1. at least 70% and
`2. statistically superior to the responder rate for the “no-treatment” control
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`The primary endpoint was based upon the average of 2 blinded Evaluating Investigators’
`assessments of overall mid-face volume deficit. The MFVDS is a 6-point photometric scale
`that has been independently validated for use in assessing the degree of mid-face volume
`deficit in males and females, where a 1-point change was shown to be clinically different.
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`Both criteria for the primary endpoint were met:
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`• 85.6% of subjects in the Treatment Group were responders (p < 0.0001) and
`•
`the responder rate for the Treatment Group was significantly greater
`(p < 0.0001) than the responder rate for the Control Group (a difference of
`46.7 percentage points) at Month 6
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`Subjects used daily diaries to report any treatment site responses experienced during the first
`30 days after any study treatment. These treatment responses were as expected with
`implantation of an HA filler. The most frequently reported responses were tenderness
`(92.1% of subjects), swelling (85.7% of subjects), and firmness (82.3% of subjects). These
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`treatment responses were typically rated as mild to moderate in severity (80.7% of subjects)
`and lasted 2 weeks or less for the majority (55.4%) of subjects.
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`JUVÉDERM VOLUMA™ XC
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`Any treatment response that was ongoing at the end of the 30-day diary was automatically
`recorded as an adverse event (AE) by the Treating Investigator. AEs could also be reported at
`any time by subjects or Treating Investigators. The most frequent device-related AEs
`following treatment were injection site mass (i.e., lumps and bumps, 18.9% of subjects) and
`injection site induration (i.e., firmness, 14.1% of subjects). Device-related AEs were
`typically mild to moderate in severity (87.7% of events).
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`There were no unexpected histological results or unanticipated adverse device effects. One
`subject died due to a stroke one year after treatment, and the death was considered to be
`unrelated to the device or procedure. Eleven treated subjects experienced 16 serious adverse
`events (SAEs); 3 of the 16 were related to the device. The 3 device-related SAEs were
`reported in 2 subjects, and included: 1) lumps at injection sites that were treated with
`medication (hyaluronidase) and resolved with sequelae of a scar at the biopsy site, 2) an
`inflammatory reaction under the eye that was treated with medication and resolved, and
`3) nodularity in the cheek that was treated with medication and resolved.
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`Based on preclinical data, extensive clinical experience outside the US, and clinical data
`generated from the VOLUMA-002 trial proving to be consistent with what has been
`observed with global clinical experience, the effectiveness and safety of VOLUMA™ XC
`have been demonstrated, with the product meeting the pre-specified effectiveness criteria
`while maintaining an acceptable safety profile. This briefing book describes the
`appropriateness of VOLUMA™ XC for correction of mid-face volume deficit and details the
`results of the VOLUMA-002 clinical study.
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`6. CLINICAL NEED FOR MID-FACIAL VOLUMIZING
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`JUVÉDERM VOLUMA™ XC
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`Mid-face volume loss is one of the changes that takes place in varying degrees as people age.
`As the population of Americans seeking the aesthetic, psychological, and social benefits of
`cosmetic procedures has increased significantly over the last decade, treatment of age-related
`volume loss represents a growing need in the field of cosmetic medicine.
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`As is evidenced by 14.6 million cosmetic procedures performed in 2012,3 which represents a
`98% increase since 2000, cosmetic procedures have become more socially accepted, and
`facial rejuvenation is more than a trivial indulgence. For many, looking young and vibrant
`has become an important aspect of their career development, earning potential, social
`interaction, and self-esteem.4 The youthful face is characterized by a round, full mid-face
`across the cheek and malar area with prominent cheekbones.5-9 Although gender, ethnic, and
`cultural differences must also be considered,10 the zygomaticomalar complex has been
`described as the “hallmark of youth” (shown in Figure 2 below).11 Universally, the mid-
`facial striated muscles, combined with the skin and subdermal fat, create an anterior
`convexity from the lower eyelid onto the cheeks, forming a smooth S-shape when viewed
`from an oblique angle.8,12
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`Figure 2. Zygomaticomalar Complex
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`Zygomaticomalar
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`Surgical options to treat volume loss in the mid-face include mid-face lift, cheek implants,
`and lower lid blepharoplasty with fat transposition.13 However, surgery requires significant
`time for recovery and exposes the patient to the inherent risks of general anesthesia.
`Rejuvenation from a pear-shaped to a heart-shaped face should fundamentally involve the
`process of volume redistribution,12 with an emphasis on “push” filling (i.e., volumizing)
`instead of “pull” surgery (i.e., face-lifting) — the new paradigm for aesthetic medicine.5
`
`Autologous fat transfer is one filling or volumizing option.14-18 However, it requires an
`additional, invasive procedure to harvest the fat, which adds to the risks of this type of
`treatment. Additionally, patients with little fat available for harvest may not be good
`candidates for the procedure. The technique for fat transfer is meticulous,14 but the results
`are unpredictable due to variable fat cell survival, which may lead to insufficient duration of
`correction.
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`The key to minimally invasive rejuvenation of the mid-facial area is volume restoration
`through re-inflation and re-contouring with injectable dermal fillers.10 Dermal fillers act by
`taking up space under and thereby pushing against the skin, providing volume and smoothing
`the surface. Appropriate volumetric augmentation of the malar area (i.e., the malar bone and
`zygomatic arch) produces the greatest aesthetic and volumetric change in the contour of the
`cheek, maximizes the projection of the zygomaticomalar eminence, and accentuates the
`lateral cheekbone, creating a high, arched appearance.19 Injection of fillers inferiorly and
`laterally to the lateral canthus have been reported to make the malar area fuller, lifting the
`upper cheek skin and restoring the desirable shape of the face.6
`
`There are currently no FDA-approved treatments for patients with age-related mid-face
`volume deficit. As detailed in Section 7, two injectable dermal fillers are currently
`FDA-approved in the US for volumization of the mid-face, but only in patients with
`HIV-associated lipoatrophy: Radiesse® (calcium hydroxylapatite particles suspended in a gel
`carrier consisting primarily of water and glycerin) and Sculptra® (poly-L-lactic acid).
`Radiesse® achieves its volumizing effect by occupying space in the injection site. The
`mechanism of action of Sculptra® involves creating a ‘scaffold’ which promotes the
`formation of new collagen by the body, rather than by directly replacing lost volume.
`
`HA has emerged as an ideal compound for cosmetic and restorative augmentation of the face,
`with a history of safe and effective use in the correction of facial wrinkles and folds in the
`United States beginning in 2003. Due to its mechanism of action (directly replacing lost
`volume), HA-based dermal fillers provide instant results, allowing the patient and physician
`to achieve the desired effect during treatment. HA-based dermal fillers are chemically
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`crosslinked to increase persistence in the body and are naturally broken down over time,
`providing temporary effects that last up to 12 months or sometimes longer, without the risks
`associated with surgery or permanent fillers.10
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`JUVÉDERM VOLUMA™ XC
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`Numerous publications have described the use of HA-based dermal fillers for mid-face
`volumizing.5,6,8,10,11,17,20-30 Literature suggests HA-based dermal fillers are the “ideal
`sculptural facial rejuvenation agents, providing a more natural and youthful countenance with
`greater safety and convenience for the aesthetic subject.”5 Despite the documented use of
`HA fillers for mid-face augmentation, there are currently no HA fillers approved in the US
`for this indication.
`
`With the paradigm of facial rejuvenation focusing on restoring the features of a youthful face
`through volumization, there is a need for safe and effective treatment options for correction
`of mid-face volume loss for patients seeking treatment of this facial region. While recent
`advancements in medicine have produced an array of non-surgical, minimally invasive
`cosmetic treatments for wrinkle correction, the current treatment options for cheek
`augmentation for the general aging population are limited to plastic surgery and autologous
`fat transfers. Based on experience with the members of the approved JUVÉDERM® family
`of HA-based dermal fillers, and with patient needs and expectations in mind, Allergan
`designed VOLUMA™ XC specifically to be a mid-face dermal filler. Patients may want to
`look younger and feel more confident but with only a subtle change in appearance that does
`not suggest a facial treatment was performed. Therefore, Allergan conducted
`VOLUMA-002, a pivotal clinical study to assess the safety and effectiveness of VOLUMA™
`XC as a minimally-invasive option for those desiring age-related mid-face volume
`restoration.
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`7. DERMAL FILLER REGULATORY HISTORY
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`JUVÉDERM VOLUMA™ XC
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`
`Various types of dermal filler materials have been approved by the FDA including
`absorbable, biodegradable biologic materials such as collagen and HA, absorbable synthetic
`materials (including poly-L-lactic acid and calcium hydroxylapatite), and a nonabsorbable
`material (polymethylmethacrylate microspheres). Below is a chronological list of the key
`FDA approvals organized by type of dermal filler material.
`
`• Collagen
`(cid:131) Zyderm® /Zyplast® (bovine collagen) were approved under PMA P800022 in
`1981/1985 (respectively) for use in the dermis for correction of contour
`deficiencies of this soft tissue
`(cid:131) Fibrel® (bovine collagen) was approved under PMA P850053 in 1988 for the
`correction of depressed cutaneous scars
`(cid:131) CosmoDerm® (recombinant human collagen) was approved under
`PMA P800022 in 2003 for injection into the superficial papillary dermis for
`correction of soft tissue contour deficiencies
`(cid:131) CosmoPlast® (recombinant human collagen) was approved under
`PMA P800022 in 2003 for injection into the mid to deep dermis for correction
`of soft tissue contour deficiencies, such as wrinkles and acne scars
`(cid:131) Evolence® (porcine collagen) was approved under PMA P070013 in 2008 for
`the correction of moderate to deep facial wrinkles and folds
`
`• HA
`(cid:131) Restylane® was approved under PMA P020023 in 2003 for injection into the
`mid to deep dermis for correction of moderate to severe facial wrinkles and
`folds
`(cid:131) Hylaform®/Captique®/Prevelle® (avian-derived HA) were approved under
`PMA P030032 in 2004/2004/2008 (respectively) for injection into the mid to
`deep dermis for correction of moderate to severe facial wrinkles and folds
`(cid:131) JUVÉDERM®, including JUVÉDERM® Ultra and JUVÉDERM® Ultra Plus,
`was approved under PMA P050047 in 2006 for use in mid to deep dermis for
`correction of moderate to severe facial wrinkles and folds
`(cid:131) Elevess™ (HA with lid