SCULPTRA Aesthetic (First Treatment Session: N = 116) Cosmoplast (First Treatment Session: N = 117) Severity of Adverse Event a Moderate n.

Transcription

1 SCULPTRA AESTHETIC Rx Oly (ijectable poly-l-lactic acid) The Sculptra implat package (i.e., lyophilized vials ad syrige) are provided sterile. Cautio: Federal (USA) law restricts this device to sale by or o the order of a licesed physicia or properly licesed practitioer. Iformatio for the use of SCULPTRA is provided i this Labelig for Physicias ad the Istructios for Use, as well as i Labelig for Patiets. BEFORE USING SCULPTRA PLEASE READ THE FOLLOWING INFORMATION THOR- OUGHLY. Please direct ay questios to saofi-avetis U.S. LLC Bridgewater, NJ 08807; DEVICE DESCRIPTION SCULPTRA is a ijectable implat cotaiig microparticles of poly-l-lactic acid (PLLA), carboxymethylcellulose (USP), o-pyrogeic maitol (USP) ad sterile water for ijectio (USP). SCULPTRA is available i mg dose vials ad is to be recostituted prior to use by the additio of 5 ml of Sterile Water for Ijectio, USP (SWFI) to form a sterile o-pyrogeic suspesio. INTENDED USE / INDICATIONS SCULPTRA is idicated for use i immue-competet people as a sigle regime for correctio of shallow to deep asolabial fold cotour deficiecies ad other facial wrikles i which deep dermal grid patter (cross-hatch) ijectio techique is appropriate. (This correspods to Wrikle Assessmet Scores (WAS) of 2 to i Figure 2 ad the cross-hatch ijectio techique preseted i Figures 3 7 i the Istructios for Use Sectio). CONTRAINDICATIONS SCULPTRA should ot be used i ay perso who has hypersesitivity to ay of the compoets of SCULPTRA (see DEVICE DESCRIPTION). SCULPTRA should ot be used i patiets with kow history of or susceptibility to keloid formatio or hypertrophic scarrig. WARNINGS SCULPTRA has uique ijectio requiremets, which iclude ijectio with tuelig techique i a grid patter that is medial to the asolabial fold cotour defect that is to be corrected. (see Figures 3 7 i the INSTRUCTIONS FOR USE). The safety of other methods of ijectio has ot bee evaluated i cliical studies. Do ot overcorrect (overfill) the cotour deficiecy of the asolabial fold cotour defect because the depressio is expected to gradually improve durig several weeks after ijectio as the treatmet effect of SCULPTRA occurs (see INSTRUCTION FOR USE - Patiet Treatmet). SCULPTRA must ot be implated ito blood vessels. Implatatio of SCULPTRA ito dermal vessels may cause vascular occlusio, ifarctio or embolic pheomea. SCULPTRA use at specific sites i which a active iflammatory process (ski eruptios such as cysts, pimples, rashes or hives) or ifectio is preset should be deferred util the iflammatory process has resolved ad is cotrolled. Ijectio site reactios to SCULPTRA have icluded delayed occurrece of subcutaeous papules ad odules, hematoma, bruisig-ecchymosis, bleedig, edema, discomfort, iflammatio, ad erythema. The subcutaeous papules ad odules were ofte cofied to the ijectio site, typically palpable, asymptomatic ad o-visible, occurrig to moths after ijectio ad had a prologed time course to resolutio. See ADVERSE EVENTS sectio for details. The kietics of SCULPTRA resorptio i humas has ot bee determied. I a itradermal implatatio study i rabbits all aimals had several relatively large remats of ijectable PLLA visible at 6 weeks after implatatio. The tissue respose to ijectable PLLA was geerally greater tha the vehicle or egative plastic cotrols ad was described as a chroic, graulomatous reactio characterized by foreig body giat cells ad macrophages. The tissue reactio was cofied to the area betwee particles, did ot ivolve the surroudig tissue ad was ot uexpected, because it was cosistet with the persistet ad particle ature of ijectable PLLA. PRECAUTIONS SCULPTRA should oly be used by a physicia traied to correct shallow to deep asolabial fold cotour deficiecies ad other facial wrikles, i which deep dermal grid patter (cross-hatch) ijectio techique is appropriate, after the physicia is fully familiar with the product, WAS, product educatioal materials, ad the etire package isert ad patiet labelig. The safety ad effectiveess of ijectig Sculptra : 1) i larger amouts, 2) at differet frequecies, 3) at aatomic sites differet tha the deep dermis of the asolabial folds, ) with differet techiques, or 5) at aatomic sites that have had previous dermal filler ijectios, (icludig previous SCULPTRA ijectio), have ot bee evaluated. Log term safety ad effectiveess of SCULPTRA beyod 25 moths after last ijectio have ot bee ivestigated i cliical trials. The safety ad effectiveess of SCULPTRA for use i the lips has ot bee evaluated. Do ot iject ito the red area (vermillio) of the lip. SCULPTRA should be ijected ito the deep dermis. Superficial ijectios may be associated with icreased local adverse evets such as odules ad papules. Take special care whe usig SCULPTRA i patiets with thi ski. Please refer to PATIENT TREATMENT for ijectio techique istructio. SCULPTRA ijectio i the peri-orbital area has ot bee studied. A icreased risk of papules ad odules has bee reported i published literature after ijectios i the periorbital area. Safety ad effectiveess of SCULPTRA has ot bee evaluated i who are pregat, lactatig, breast feedig, or uder 18 years of age. Safety ad effectiveess of SCULPTRA has ot bee evaluated i with the followig: history of keloid formatio, hypertrophic scarrig, coective tissue disease, active iflammatory coditios, bleedig disorders, active hepatitis, serious abormalities i laboratory fidigs, disease such as cacer, stroke ad or myocardial ifarctio, o ay immuosuppressive therapy, ad/or with ay other prior or cocomitat treatmet at the SCULPTRA treatmet site. Safety ad effectiveess of SCULPTRA has ot bee systematically evaluated with local aesthetics, other drugs or devices used durig the same treatmet sessio. The safety ad effectiveess of the volume ratio of SCULPTRA mixed with local aesthetic or ay drug or device has also ot bee assessed. Other filler products should ot be directly mixed with SCULPTRA. No studies of iteractios of SCULPTRA with drugs or other substaces or implats have bee made. The volume of SCULPTRA ijectio per surface area of a tuelig or threadig ijectio grid has ot bee assessed for ay WAS. It is ot kow whether SCULPTRA is radiopaque. The microparticles of SCULPTRA may be visible o computer tomography (CT) scas, magetic resoace imagig (MRI), ultrasoud or stadard, plai radiography. Patiets should be iformed that the device may be radiopaque, so that they ca iform their health care professioals, icludig radiologists. Safety ad effectiveess data cliical trials of SCULPTRA i o- Caucasias are limited. As with all trascutaeous procedures, SCULPTRA ijectio carries a risk of ifectio. Stadard precautios to miimize ifectios associated with itradermal ijectable materials should be followed. As with all ijectios, patiets with coagulatio defects or o cocurret ati-coagulat therapy are at icreased risk for hematoma formatio, bruisig ad/or bleedig at the ijectio site. As with all ivasive procedures, SCULPTRA sessios should be coducted with aseptic techique. Observe uiversal precautios to miimize risks of potetial cotact with patiet body fluids such as blood at the ijectio site. After use, treatmet syriges ad eedles are cosidered cotamiated biohazards. Hadle ad dispose cotamiated syriges ad eedles i accordace with accepted medical practice ad applicable local, state ad federal requiremets. The patiet should be iformed that he or she should miimize exposure of the treatmet area to su ad avoid UV lamp exposure util ay iitial swellig ad redess has resolved. If laser treatmet, chemical peelig or ay other procedure based o active dermal respose is cosidered after treatmet with SCULPTRA, there is a possible risk of elicitig a iflammatory reactio at the implat site. This also applies if SCULPTRA is admiistered before the ski has healed completely after such a procedure. SCULPTRA vials are for sigle patiet use oly. Do ot reuse or resterilize the vial. Do ot use if the package or vial is opeed or damaged. ADVERSE EVENTS Cliical trial Cotrolled phase study (0 13 moths) A prospective, radomized cliical study was coducted at 10 ceters i the US. Two hudred ad thirty three (233), immue-competet ad o-pregat ad o-breast feedig with previously utreated asolabial fold wrikles ad WAS of 2 through received bilateral ijectios of either SCULPTRA or i both asolabial fold wrikles durig a maximum of sessios over 9 weeks. Study treatmet was plaed to be stopped whe the right ad left asolabial fold wrikle reached WAS of 1 or 0, or the maximum of treatmet sessios were completed. Adverse evets reported i subject diaries after iitial treatmet are summarized i Tables 1 (itesity) ad 2 (duratio) below. Adverse evets described i the physicia case reports are summarized i Table 3 below. Ijectio Procedure Related Evet Swellig TABLE 1 INTENSITY OF ADVERSE EVENTS AFTER THE INITIAL TREATMENT SESSION, RECORDED IN THE 1 DAY SUBJECT DIARY (Cotrolled Phase, 0 13 moths) All-Treated Populatio: Per subject reportig (%) SCULPTRA (First Treatmet Sessio: N = 116) Mild Severity of Adverse Evet a Moderate Severe Missig reportig (%) (First Treatmet Sessio: N = 117) Mild Severity of Adverse Evet a Moderate Severe 9 (81.0) (65.0) Missig 1

2 Ijectio Procedure Related Evet Tederess Redess Post-Ijectio Site Pai Bruisig Bleedig Site(s) Itchig Nodules / papules / lumps TABLE 1 INTENSITY OF ADVERSE EVENTS AFTER THE INITIAL TREATMENT SESSION, RECORDED IN THE 1 DAY SUBJECT DIARY (Cotrolled Phase, 0 13 moths) All-Treated Populatio: Per subject (cotiued) reportig (%) SCULPTRA (First Treatmet Sessio: N = 116) Mild Severity of Adverse Evet a Moderate Severe Missig reportig (%) (First Treatmet Sessio: N = 117) Mild Severity of Adverse Evet a Moderate Severe 9 (81.0) (70.9) (77.6) (75.2) (70.7) (55.6) (6.7) (2.7) (33.6) (36.8) (19.8) (29.1) (3.) (12.0) Other b 19 (16.) (18.8) (97.) (9.0) a Subjects experiecig multiple episodes of a give adverse evet are couted oce for that evet withi the most severe category. b Subjects who reported multiple evets i the Other category are couted oly oce withi the most severe category. Adverse Evets reported as Others are headache, dry ski, ski peelig, rash at ijectio, pimples, improvemet of allergy symptoms, eedle marks, sius pressure, bruisig, mouth sores, tederess ad twitchig of ostril. Missig Ijectio Procedure Related Evet Swellig Tederess Redess Post- Ijectio Site Pai Bruisig Bleedig Site(s) Itchig Nodules / papules / lumps TABLE 2 DURATION OF ADVERSE EVENTS AFTER THE INITIAL TREATMENT SESSION, RECORDED IN THE 1 DAY SUBJECT DIARY (Cotrolled Phase, 0 13 moths) All-Treated Populatio: Per subject reportig SCULPTRA (First Treatmet Sessio: N = 116) 1 hour 1 2 hrs Duratio of Adverse Evet a Missig reportig 1 hour (First Treatmet Sessio: N = 117) 1 2 hrs Duratio of Adverse Evet a 9 (81.0) (65.0) (81.0) (70.9) (77.6) (75.2) (70.7) (55.6) (6.7) (2.7) (33.6) (36.8) (19.8) (29.1) (3.) (12.0) Other b 19 (16.) (18.8) (97.) (9.0) a Subjects experiecig multiple episodes of a give adverse evet are couted oce for that evet withi the logest duratio category. b Subjects who reported multiple evets i Other category are couted oly oce withi the logest duratio category. For list of adverse evets categorized as other, see table Missig 2

3 TABLE 3 PHYSICIAN REPORTED* ADVERSE EVENTS AFTER ALL TREATMENTS REGARDLESS OF RELATIONSHIP TO THE DEVICE OCCURRING IN 1% OF SUBJECTS (Cotrolled Phase, 0 13 moths) All-Treated Populatio: Per subject ADVERSE EVENTS (MedDRA Preferred Term) SCULPTRA N = 116 N (%) N = 117 N (%) ijectio site pai 11 (9.5) 12 (10.3) applicatio site odule** 10 (8.6) 11 (9.) applicatio site papule*** 10 (8.6) (3.) asopharygitis 7 (6.0) 9 (7.7) headache 5 (.3) (3.) ijectio site erythema (3.) 38 (32.5) ace 3 (2.6) (3.) pai 3 (2.6) 2 (1.7) ijectio site dermatitis 3 (2.6) 1 (0.9) hypertesio 3 (2.6) 0 (0.0) ijectio site haemorrhage 2 (1.7) 6 (5.1) swellig 2 (1.7) 2 (1.7) fracture 2 (1.7) 2 (1.7) uriary tract ifectio 2 (1.7) 2 (1.7) streptococcal ifectio 2 (1.7) 0 (0.0) tooth abscess 2 (1.7) 0 (0.0) sycope vasovagal 2 (1.7) 0 (0.0) cough 2 (1.7) 0 (0.0) ijectio site pruritus 1 (0.9) 12 (10.3) siusitis 1 (0.9) 6 (5.1) applicatio site dryess 1 (0.9) 5 (.3) iflueza 1 (0.9) 5 (.3) ijectio site swellig 1 (0.9) (3.) brochitis 1 (0.9) 2 (1.7) upper respiratory tract ifectio 1 (0.9) 2 (1.7) ijectio site discoloratio 0 (0.0) 2 (1.7) TABLE 3 PHYSICIAN REPORTED* ADVERSE EVENTS AFTER ALL TREATMENTS REGARDLESS OF RELATIONSHIP TO THE DEVICE OCCURRING IN 1% OF SUBJECTS (Cotrolled Phase, 0 13 moths) All-Treated Populatio: Per subject (cotiued) ADVERSE EVENTS (MedDRA Preferred Term) SCULPTRA N = 116 N (%) N = 117 N (%) ijectio site eczema 0 (0.0) 2 (1.7) ski tightess 0 (0.0) 2 (1.7) * Icludes all with odules ad papules regardless of duratio ** Applicatio site odule is a lesio equal to or greater tha to 5 mm, typically palpable, asymptomatic ad o-visible ***Applicatio site papule is a lesios less tha 5 mm, typically palpable, asymptomatic ad o-visible Adverse evets that occurred with SCULPTRA at a icidece of <1%: Acrochordo, axiety, colitis, cotusio, coreal abrasio, cyst, depressio, dermatitis, eczema, gastritis, herpes simplex, hypercholesterolemia, hypersesitivity, hypothyroidism, ijectio site desquamatio, ijectio site rash, lower respiratory ifectio, lymphadeopathy, migraie, muscle ijury, muscle twitchig, myalgia, osteoarthritis, osteopeia, pruritus, rheumatoid arthritis, gastroeteritis, ski burig sesatio, spider vei, staphylococcal ifectio, stress symptoms, tooth ifectio, toothache, vagial ifectio. Extesio Phase Study (13 to 25 moths) A total of 106 treated with SCULPTRA i the iitial 13 moth study were followed for a additioal 12 moths (25 moths total) after their last treatmet. Oly SCULPTRA -related adverse evets were collected o the physicia case report forms. Five ew device-related adverse evets were reported i three : 2 subcutaeous papules (1.9%), 1 odule (0.9%) ad 2 ijectio site pai (0.9%). Nodules ad Papules I the cotrolled cliical study the percetage of with odules ad/or papules was greater after SCULPTRA [(17.2% (20/116)] tha after the cotrol treatmet [(12.8%) (15/117)]. This reflects 8 Sculptra who experieced odules, 10 Sculptra patiets who experieced papules ad 2 Sculptra who experieced both odules ad papules. After the first SCULPTRA ijectio sessio, time to oset for odules was 160 (media) ad 209 (mea) ad for papules 55 (media) ad 159 (mea). After SCULPTRA ijectio, the duratio of odules was 100 (media) ad 180 (mea), for papules was 110 (media) ad 176 (mea). Oe subject with a papule required a sigle itralesioal corticosteroid ijectio ad the evet resolved. For 3 with odules/papules, o iformatio o outcome was available at the ed of the 25 moth extesio phase study. For all remaiig, odules/papules resolved spotaeously. Noe of these evets were reported as a serious adverse evet by the ivestigator. Table cotais, for the SCULPTRA (0 25 moths) ad (0 13 moths) groups, summaries of the umber of odules ad papules per baselie ski type, age group, ad race stratified by baselie WAS. Summaries of the time to oset ad duratio of odules ad papules, stratified by baselie WAS are also preseted. Baselie (Pre-Ijectio, before first treatmet) WAS TABLE SUMMARY OF NODULES AND PAPULES, SCULPTRA AESTHETIC (SA) ad COSMOPLAST (COS) ALL Treatmet SA COS SA COS SA COS SA COS SA COS Number of pt ijected (N) Patiets with odule 0 0% Patiets with papule 0 0% Patiets Nodules or Papules per Fitzpatrick Ski Type 0 0% 0 0% 7.3% % 9.8% 1 2.% Demographics Fitzpatrick Ski Type = Fitzpatrick Ski Type = Fitzpatrick Ski Type = Fitzpatrick Ski Type = Fitzpatrick Ski Type = Fitzpatrick Ski Type = Patiets Nodules or Papules per age group Patiets <35 y.o Patiets y.o % % % 1 1.8% 2 1.3% 0 0% 1 5.9% % % % 11 9.% 3.% 3

4 Baselie (Pre-Ijectio, before first treatmet) WAS TABLE SUMMARY OF NODULES AND PAPULES, SCULPTRA AESTHETIC (SA) ad COSMOPLAST (COS) (cotiued) ALL Treatmet SA COS SA COS SA COS SA COS SA COS Patiets >55 y.o Patiets Nodules or Papules per race Caucasia Hispaic Black / Asia /Other Nodules - media to evet oset Nodules - mea to evet oset Nodules time to oset Time () first device ijectio to start of evet [media, mea, mi, max] miimum maximum Papule - media to evet oset Papules - mea to evet oset Papules time to oset miimum maximum Evet Duratio, [media, mea, mi, max] Nodule - media duratio Nodule - mea duratio Nodule duratio miimum maximum Papule - media duratio Papule - mea duratio Papules duratio miimum maximum No sigificat associatios were foud betwee icidece of odule/papules ad geographic site, volume ijected, umber of treatmet sessios, subject characteristics at baselie (Fitzpatrick ski type, age ad race), or baselie WAS (pre-ijectio, before first treatmet). Post Marketig Surveillace The followig adverse evets were received post-marketig surveillace for SCULP- TRA ad SCULPTRA i the US ad outside the US, that were ot observed i the cliical trials with Sculptra : allergic reactio, agioedema (Quicke s edema), applicatio site discharge, fatigue, hypersesitivity reactio, hypertrophy of ski, ijectio site abscess, ijectio site atrophy, ijectio site fat atrophy, ijectio site grauloma (icludig ectropio), ijectio site iduratio, lack of effectiveess, malaise, periorbital odules, photosesitive reactio, scar ad ski discoloratio, ski ifectio (icludig cellulitis (facial) ad staphylococcal ifectio), ski rash, ski roughess, ski sarcoidosis, telagiectasias, urticaria, visible odules with or without iflammatio or discoloratio. Scarrig, mostly a o-serious evet, has bee reported i associatio with ski discoloratio, odules, lumps, iduratios, graulomas, hyperpigmetatio, hypertrophic scars, ad suspicio of keloid formatio. Time to oset raged 1 moth to 2 moths post-sculptra ijectio ad outcome raged improved to o-goig at last cotact. Ski discoloratio has bee reported as a o-serious evet, typically reported i associatio with lumps ad odules. It has also bee reported with blachig ad telagiectasias. Time to oset usually raged 1 moth to 12 moths post-ijectio. Outcome raged improved to o-goig at last cotact. Serious adverse evets have ifrequetly bee reported. The most commoly reported serious adverse evets (by MedDRA Preferred Term) were ijectio site odule, grauloma, odule, erythema, pai, iflammatio, edema, hypersesitivity ad pruritus. Regardig these ifrequetly reported adverse evets the followig describes serious adverse evets with a frequecy greater tha 5 reported evets: Ijectio site odules mostly occurred several moths post-ijectio, with time to oset ragig 1 2 moths to 1 moths post-last ijectio. I some cases, the odules were reported to resolve spotaeously or followig treatmet with itralesioal corticosteroids; others have bee described with a prologed duratio of up to 2 years. For those odules that were larger i size, occurrig i difficult aatomical regios (e.g. lower eyelid) or persisted after other treatmets such as itralesioal corticosteroids failed, surgical excisio of the device was required. Serious graulomas usually occur several moths after ijectio, i few cases oset was more tha 1 year post-ijectio. While evets were reported as grauloma, biopsy cofirmatio was made o few cases. Treatmet raged subcisio or itralesioal corticosteroid with subsequet improvemet, to surgical extractio. Of the few grauloma cases that required hospitalizatio, these were associated with ifraorbital use or ijectio i the lip vermilio. For cases where iformatio was available the patiets were recoverig followig treatmet. Serious erythema, serious pai, ad serious pruritus reported with bruisig ad heat sesatio, were reported withi 2 hours post-ijectio. Treatmet icluded corticosteroids, ati-histamies ad/or ati-iflammatories. Evets resolved withi 7 10 post-ijectio without sequelae ad with o sigificat impact o daily life. Serious edema has bee reported i associatio with erythema, pai, ad heat sesatio. The symptoms were mostly temporary, ad with o sigificat impact o the quality of daily life reported. Treatmet icluded corticosteroids, ati-histamies ad/or ati-iflammatories. Recovery occurred withi 7 10 without sequelae. Serious hypersesitivity reactios have bee reported maily i associatio with facial swellig ad Quicke s edema, with ppearig 1 day to 1 week post-ijectio. Patiets recovered without sequelae after treatmet with itraveous corticosteroids ad ati-histamies. Serious ifectios such as subcutaeous abscesses, cellulitis, folliculitis, ad methicilli-resistat Staphylococcus aureus at the ijectio site, have bee reported. Time to oset of evet raged 1 day to oe week. Of these cases a few required hospitalizatio with admiistratio of itraveous atibiotics. All patiets recovered or were recoverig at the last cotact.

5 CLINICAL STUDIES A. Study Desig Cotrolled Phase Study (0 13 Moths): The safety ad effectiveess of SCULPTRA use to correct WAS 2 (shallow) to (deep) asolabial fold wrikles was evaluated i a radomized, multiceter, evaluator blided, cotrolled study of otherwise healthy ad immue-competet, as well as ot pregat or breast-feedig with previously utreated asolabial fold wrikles ad WAS of 2 through. The received bilateral ijectios of either SCULPTRA or i both asolabial fold wrikles durig a maximum of sessios over 9 weeks. Study treatmet was plaed to be stopped whe both asolabial fold wrikle reached optimal correctio of WAS equal to 1 or 0, or util the maximum of treatmet sessios were completed. The study recorded adverse evets i a subject diary after each treatmet visit, ad were followed by ivestigators at Week 3 ad Moths 3, 6, 9, ad 13, after the last ijectio sessio. Stadardized photographs were take at screeig, before each ijectio sessio ad at each follow up visit. Extesio Phase Study (13 25 Moths): Study who had received SCULPTRA were followed for safety ad efficacy at moths 19 ad 25 after the last ijectio sessio. Stadardized photographs were take at each follow-up visit. B. Study Edpoits Cotrolled Phase Study (0 13 Moths): The primary efficacy edpoit was defied as the differece betwee SCULPTRA ad cotrol cohorts o the mea chage baselie i the WAS of the asolabial folds at the 13 moth follow-up time poit as determied by the Blided Evaluatio Committee (BEC). Evaluatio was based o the 6-poit photo-umeric Wrikle Assessmet Scale (see INSTRUCTIONS FOR USE) Optimal correctio was defied as a WAS of 0 or 1. Secodary effectiveess edpoits were: 1) Mea chage pre-treatmet baselie i the WAS as determied by the BEC at the o-primary follow-up time poits (Week 3 ad Moths 3, 6, 9, followig the last treatmet); 2) Treatmet success rate defied as the proportio of patiets with a photographic WAS of <2 as defied by the BEC at each follow-up time poit; 3) Ivestigator/Subject Global Assessmets (= Excellet Improvemet, 3= Much Improved, 2= Improved, 1= No Chage, 0= Worse) ad the Subject Satisfactio Scores (= Excellet, 3= Very Good, 2= Good, 1= Satisfactory, 0= Not Satisfied) at each follow-up time poit compared betwee treatmets; ad ) Time to peak correctio, defied as the legth of time betwee pre-treatmet baselie ad the first time poit at which the best score assessed by the BEC was obtaied over the legth of the follow up period. Degree of peak correctio was also assessed. Extesio Phase Study (13 25 Moths): All secodary effectiveess edpoits described above were evaluated for the log- term extesio study time poits at 19 ad 25 moths. C. Study Populatio Cotrolled Phase Study (0 13 Moths): A total of 233 (age 26 to 73 years) were radomized ad treated. At the coclusio of 13 moths 106 out of 116 SCULPTRA ad 111 out of 117 cotrol completed the cotrolled phase of the study. Demographics are outlied i Table 5. Extesio Phase Study (13 25 Moths): Oe hudred ad six, who had received SCULPTRA ad completed the cotrolled phase study, etered the extesio phase. The demographic ad backgroud characteristics of all were similar to the overall populatio radomized i the cotrolled phase study. At the ed of the 25 moth follow-up phase, 95 out of 106 of the completed (see Table 5). TABLE 5 STUDY POPULATION DEMOGRAPHICS Cotrolled Phase Study SCULPTRA Extesio Phase Study SCULPTRA Demographic N (%) N (%) N (%) study erollmet (radomized) Age Mea (SD) 51.2 (7.8) 51.6 (8.) 51.5 (7.9) Geder Male 3 (2.6) 10 (8.5) 3 (2.8) Female 113 (97.) 107 (91.5) 103 (97.2) Race Caucasia 96 (92.8) 89 (76.1) 86 (81.1) Black 1 (0.9) 5 (.3) 1 (0.9) Asia 0 1 (0.9) 0 Hispaic 19 (16.) 21 (17.9) 19 (17.9) Other 0 1 (0.9) 0 Fitzpatrick ski type Type I 11 (9.5) 5 (.3) 10 (9.) Type II 39 (33.6) 3 (36.8) 3 (32.1) Type III (37.9) 8 (1.0) 1 (38.7) Type IV 16 (13.8) 15 (12.8) 16 (15.1) Type V 5 (.3) (3.) (3.8) Type VI 1 (0.9) 2 (1.7) 1 (0.9) Nasolabial fold WAS before ijectio 1 6 (5.2) (3.) (3.8) 2 55 (7.6) 1 (35.3) 50 (7.2) 3 1 (35.3) 55 (7.6) 39 (36.8) 1 (12.1) 17 (1.7) 13 (12.3) completed D. Treatmets Delivered Cotrolled Phase Study (0 13 Moths): Treatmet was plaed for oe to four sessios at 3 week itervals util optimal correctio (WAS = 1 or 0) was achieved or four sessios were completed. At each treatmet with SCULPTRA, multiple deep dermal ijectios i cross hatch grid patter (see Figures 3 7 i the Istructios for Use) of ml SCULPTRA (up to a maximum of 2.5 ml per asolabial fold per sessio) were performed ito the left ad right asolabial folds accordig to product Istructios for Use. At each treatmet sessio with cotrol multiple mid to deep dermal ijectios of a average of 1.0 ml per asolabial fold per sessio were performed ito the left ad right asolabial folds accordig to product Istructios for Use. Table 6 presets the amout of Sculptra ijected as a fuctio of baselie wrikle severity. Baselie (Pre-Ijectio, before first treatmet) WAS Sculptra TABLE 6 SUMMARY SCULPTRA AESTHETIC AND CONTROL INJECTIONS ALL Sculptra Sculptra Sculptra Sculptra Number of pt ijected (N) Sessio 1 Ijectio volume, ml Mea Media Rage 2.0, ,.0 1.5,5.0 1.,.0 1.7, , , , , ,6.0 5

6 Baselie (Pre-Ijectio, before first treatmet) WAS Sessio 2 Sessio 3 Sessio Volume Ijected, ml Number of sessios TABLE 6 SUMMARY SCULPTRA AESTHETIC AND CONTROL INJECTIONS (cotiued) ALL Mea Media Rage 2.0, ,2.0 1., ,.0 0., ,.0 2.7, ,5.0 0., , Mea Media Rage 1.6,.5 3.0, , ,.0 0.9, , ,.6 0.6,.0 0.8, , Mea Media Rage 3.0,.0 2.0, , , ,5.0 0.,.0 3.0, , ,5.0 0.,.0 Mea Media Rage.7,17.9.0,9.0.5, , , , , , , ,16.0 Number of Sessios Mea Number of Sessios Rage 1.0,.0 1.0,.0 1.0,.0 1.0,.0 1.0,.0 1.0,.0 3.0,.0 1.0,.0 1.0,.0 1.0,.0 The mea total volume ijected per subject was 11.7 ad 6.2 ml for SCULPTRA ad cotrol treatmets, respectively. The mea total volume ijected per sessio, for both asolabial folds, for SCULPTRA was 3.7 ml ad 2. ml for cotrol. A mea umber of 3.2 ad 2.6 ijectio sessios were required for SCULPTRA ad cotrol, respectively to achieve WAS of 1 or 0, or util the maximum of treatmet sessios with 3 week iterval was reached i the study populatio. Extesio Phase Study (13 25 Moths): Of the 106 who etered the extesio phase study, 105 (99%) did ot receive ay additioal SCULPTRA treatmets after optimal correctio was achieved i the cotrolled study. Oe subject i the extesio phase study received oe treatmet sessio of SCULPTRA at moth 19. EFFECTIVENESS RESULTS: Cotrolled Phase (0 13 moth) ad Extesio Phase (13 25 Moths) Study Results: Primary Effectiveess Edpoit - The differece betwee SCULPTRA ad cotrol cohorts o the mea chage baselie i the WAS of the asolabial folds at the 13 moth follow up time poit as determied by the Blided Evaluatio Committee was predicted to be 1.0 uit. For the iteded use populatio, Figure 1 demostrates the observed WAS chage pre-treatmet baselie through each treatmet ad follow-up poit, idividually for pre-treatmet WAS = 2, 3, ad. Table 7 presets the WAS chage pre-treatmet baselie at each time poit stratified by pre-treatmet baselie score. SCULPTRA (N=116) demostrated improved WAS as compared to cotrol (N=117) i correctig the cotour deficiecy of shallow (W=2) to deep (W=) asolabial folds at 13 moths follow up after a sigle treatmet regime of up to four sessios of 2.5 ml maximum ijectios to the deep dermis with 3 week itervals. Durig the extesio phase study (19 ad 25 moths follow up) SCULPTRA (N=106) cotiued to demostrate improvemets i WAS. Figure 1 6

7 TABLE 7 WAS SUMMARY AT EACH TIME POINT STRATIFIED BY BASELINE SCORE (Cotrolled ad Extesio Phase Study, 0 25 moths) Itet-to-treat Populatio, SCULPTRA Subjects oly Baselie WAS Baselie (Pre- Ijectio) Trt Sessio 2 Trt Sessio 3 Trt Sessio Wk 3 Moth 3 Moth 6 Moth 9 Moth 13 Moth 19 Moth 25 N Mea 1.33 (0.086) 1.50 (0.25) 1.39 (0.111) 1.06 (0.17) 1 Media Mea Chage Baselie P-Value for Chage Baselie N/A 0.17 (0.236) (0.056) (0.056) 1.13 (0.200) (0.190) 1.33 (0.289) (0.22) 1.10 (0.155) (0.113) 1.0 (0.201) 0.03 (0.111) 1.08 (0.337) (0.220) 1.17 (0.180) (0.068) 1.25 (0.160) (0.08) N/A N Mea 2.19 (0.037) 2.02 (0.060) 1.75 (0.112) 1.69 (0.17) 2 Media Mea Chage Baselie P-Value for Chage Baselie N/A (0.057 ) -0.6 (0.107) (0.15) 1.63 (0.073) (0.077) 1.6 (0.070) (0.071) 1.69 (0.051) (0.05) 1.60 (0.063) (0.062) 1.60 (0.063) (0.067) 1.51 (0.082) (0.08) 1.58 (0.076) (0.079) N/A < <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 N Mea 2.99 (0.03) 2.6 (0.065) 2.52 (0.067) 2.21 (0.08) 3 Media Mea Chage Baselie P-Value for Chage Baselie N/A (0.066) (0.053) (0.085) 2.21 (0.068) (0.069) 2.13 (0.066) (0.068) 2.06 (0.088) -0.9 (0.083) 2.03 (0.08) (0.078) 1.8 (0.068) (0.065) 2.08 (0.098) -0.9 (0.097) 2.03 (0.090) (0.089) N/A <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 N Mea.07 (0.078) 3.7 (0.107) 3.58 (0.129) 3.0 (0.166) Media Mea Chage Baselie P-Value for Chage Baselie N/A (0.103) -0.9 (0.112) (0.15) 3.15 (0.220) (0.232) 3.18 (0.168) -0.9 (0.167) 3.11 (0.151) (0.138) 3.09 (0.196) (0.19) 3.26 (0.169) (0.16) 3.60 (0.161) (0.108) 3.85 (0.207) (0.168) N/A <0.001 < <0.001 <0.001 <0.001 <0.001 < HOW SUPPLIED SCULPTRA is supplied as a sterile freeze-dried preparatio for ijectio i a clear glass vial, which is sealed by a peetrable stopper, covered by a alumium seal with a flip-off cap. Each carto of SCULPTRA cotais two vials of poly-l-lactic acid, sodium carboxymethylcellulose (USP), o-pyrogeic maitol (USP) NHRIC STORAGE SCULPTRA ca be stored at room temperature, up to 30 C (86 F). DO NOT FREEZE. Refrigeratio is ot required.

8 STERILITY Each vial of SCULPTRA is packaged for sigle-use oly. Do ot resterilize. IF THE VIAL, SEAL, OR THE FLIP-OFF CAP ARE DAMAGED, DO NOT USE AND CONTACT SANOFI-AVENTIS U.S. LLC AT INSTRUCTIONS FOR USE SCULPTRA has oly bee evaluated i immue-competet people as a sigle regime for correctio of shallow to deep asolabial fold cotour deficiecies ad other facial wrikles i which deep dermal grid patter (cross-hatch) ijectio techique is appropriate. SCULPTRA use should be limited to use i a sigle regime of up to four sessios with three week iterval usig the threadig or tuelig techique i grid patter (see Figures 3 7) to iject a maximum of 2.5 ml of SCULPTRA per site ito the deep dermis medial to the asolabial fold cotour deficiecy. The followig supplies are used with SCULPTRA but are to be provided by the ed-user: Sterile Water for Ijectio (SWFI), USP Sigle-use 5 ml sterile syrige Sigle-use 1 or 3 ml (depedig o physicia practitioer preferece) sterile syriges (at least 2) 18 G sterile eedles (at least 2) 26 G sterile eedles (several should be available) Atiseptic (such as alcohol) Recostitutio SCULPTRA is recostituted i the followig way: 1. Remove the flip-off cap the vial ad clea the peetrable stopper of the vial with a atiseptic. If the vial, seal, or flip-off cap is damaged, do ot use, ad call saofi-avetis U.S. LLC at Attach a 18 G sterile eedle to a sterile sigle-use 5 ml syrige. 3. Draw 5 mls of SWFI ito the 5 ml syrige.. Itroduce the 18 G sterile eedle ito the stopper of the vial ad slowly add all SWFI ito the vial. 5. Let the vial stad for at least 2 hours to esure complete hydratio; do ot shake durig this period. SCULPTRA ca be stored at room temperature up to 30 C (86 F) durig ad after hydratio. Refrigeratio is ot required. 6. Product should be getly agitated immediately prior to use. Agitate the vial util a uiform traslucet suspesio is obtaied. A sigle vial swirlig agitator may be used. The recostituted product is usable withi 72 hours of recostitutio. As it is a sigle use vial, discard ay material remaiig after use or after 72 hours followig recostitutio. 7. Clea the peetrable stopper of the vial with a atiseptic, ad use a ew 18 G sterile eedle to withdraw a appropriate amout of the suspesio (typically 1 ml) ito a sigle use 1 or 3 ml sterile syrige. Do ot store the recostituted product i the syrige. 8. Replace the 18 G eedle with a 26 G sterile eedle before ijectig the product ito the deep dermis. Do ot iject SCULPTRA usig eedles of a iteral diameter smaller tha 26 G. 9. To withdraw remaiig cotets of the vial, repeat steps 6 through 8. Patiet Treatmet 1. Patiet Couselig. It is ecessary to cousel the patiet ad discuss the appropriate idicatio, risks, beefits ad expected resposes to the SCULPTRA treatmet. Advise the patiet of the ecessary precautios before commecig the procedure. Before treatmet with SCULPTRA, a patiet should be provided patiet labelig ad completely iformed by the treatig physicia of the iteded use, idicatios for use, as well as the cotraidicatios, warigs ad precautios for use, expected correctio, ad possible side effects ad mode of admiistratio of SCULPTRA. Each patiet should be iformed that the amout of SCULP- TRA ad the umber of ijectio sessios will deped o the patiet s eed. A treatmet sessio to correct WAS 2 cotour deficiecies (see picture, Figure 2) of facial wrikles such as asolabial folds cosist of multiple deep dermal threadig or tuelig ijectio of ml of SCULPTRA i grid patter to a maximum of 2.5 ml per asolabial fold per sessio. Patiets should be iformed that, if eeded, their physicia may utilize a topical or a local aesthetic prior to ijectig SCULPTRA. 2. Patiet Assessmet. A complete medical history should be take to determie if SCULPTRA ijectio is appropriate. Usig the stadard wrikle assessmet score (WAS) photographs provided for patiet couselig, a patiet should be iformed of the optimal cosmetic correctio that may be expected by that patiet, ad that up to four ijectio sessios (typically three) may be eeded to achieve the desired results. Durig the iitial treatmet sessio with SCULPTRA, oly a limited correctio should be made. I cotrast to other wrikle fillers, SCULPTRA provides a gradual improvemet of the depressed area over several weeks as the treatmet effects occur. 3. Patiet Preparatio. Each ijectio sessio is to be coducted with aseptic techique ad uiversal precautios due to the potetial for cotact with patiet body fluids: blood the ijectio site. Before ijectig SCULPTRA a treatmet pla is determied ad the face mapped. The mappig is doe usig a water soluble pecil ad a grid that is parallel ad perpedicular to the asolabial fold is outlied. See Sectio 6 - Ijectig: Threadig or Tuelig Techique.. Ijectio Needle. SCULPTRA should be ijected usig a sterile 26 G eedle. SCULPTRA should ot be ijected with eedles with a diameter smaller tha 26 G or eedles that have bee bet. To maitai a uiform suspesio throughout the procedure, itermittetly agitate SCULPTRA i the syrige. Before iitial ijectio, expel a few drops of SCULPTRA through the attached 26 G eedle to elimiate air ad to check for eedle blockage. If the eedle becomes occluded or dull durig a ijectio sessio eedle replacemet is ecessary. If cloggig occurs, remove the eedle, expel a small amout of product, attach a ew sterile 26g eedle, the expel a few drops of SCULPTRA to elimiate the air ad re-check for eedle blockage. 5. Depth of Ijectio. SCULPTRA should be ijected ito the deep dermis with tuelig (threadig) techique. As per Figure 7, SCULPTRA should be ijected ito tissue that is medial to the asolabial fold wrikle defect. To guide the eedle to the deep dermal plae, create a firm eedle isertio plae by stretchig the ski (Figure 3). Figure 3 Itroduce a straight, sterile, bevel-up 26 G eedle ito the ski at a approximately 30 0 degree agle to the ski ad the advace the eedle to the deep dermis util the desired ski depth is reached (Figure ). Figure 2 Figure Oe to four treatmet sessios (typically three) might be eeded to achieve optimal correctio with a miimum of three week itervals betwee ijectio sessios. Patiets should be iformed that typically, at the ed of the ijectio sessio, they will experiece some degree of swellig due to the water (SWFI) used to recostitute SCULPTRA ad this will give the appearace of a full correctio by the ed of the ijectio sessio. Patiets should be iformed that the ijectio-related swellig typically resolves i several hours to a few, resultig i the reappearace of the origial cotour deficiecy. Patiets should also be iformed that the optimal correctio after iitial ijectio depeds o patiet s pre-treatmet asolabial fold WAS score. I the cliical study, optimal correctio at 9 weeks after iitial ijectio was most commoly foud to be a 0.5 to 1 poit decrease i WAS. 8 A chage i tissue resistace is felt whe the eedle crosses the dermis ito subcutaeous layer. If the eedle is iserted at too shallow (small) a agle or if the eedle tip is ot sufficietly advaced, the the eedle tip may be i the mid or superficial (papillary) dermis, the eedle bevel may be visible through the ski. If SCULPTRA is ijected too superficially, the ijected area will blach immediately or slightly after ijectio. If the ijected area blaches, remove the eedle ad massage the area i a circular fashio. I the evet that the blachig does ot disappear, the patiet should ot be re-ijected. 6. Ijectig: Threadig or Tuelig Techique i a Grid Patter (cross-hatch). a. Techique. Whe the eedle tip is i the deep dermal plae, the eedle agle should be lowered to degrees ad the eedle should be advaced i the deep dermal plae parallel to the surface of the ski (Figure 5).

9 Figure 5 Before ijectig SCULPTRA, always perform a reflux maeuver to avoid itravascular ijectio. If blood returs to the syrige, the eedle is i a blood vessel ad should be withdraw, pressure should be applied to the ijected area util bleedig stops ad a ew syrige should be prepared. If o blood is pulled back ito the syrige, use the threadig or tuelig techique, to deposit a thi trail of SCULPTRA by doig a retrograde ijectio whe slowly withdrawig the eedle (Figure 6). Figure 6 Based o the treatmet pla (see Sectio 3 - Patiet Preparatio), Start the first ijectio at the base of the asolabial fold. After completig the legth with ijectios parallel to the asolabial fold, the cross-hatch patter is achieved with additioal ijectios perpedicular to the first ijectio. Picture below shows a cross-hatch patter after completig the last ijectio (Figure 7). Figure 7 b. Volume per Ijectio. The maximum volume of SCULPTRA per idividual ijectio should be limited to 0.1 ml 0.2 ml, spaced at a distace of cm. Avoid overcorrectio. c. Volume per Treatmet Site. A treatmet sessio to correct WAS 2 asolabial fold cotour deficiecies cosists of multiple deep dermal threadig or tuelig ijectio of ml of SCULPTRA i grid patter to a maximum of 2.5 ml per asolabial fold per sessio. The volume of SCULPTRA per surface area of ijectio grid has ot bee determied. Durig the iitial treatmet sessios oly a limited correctio should be made. I cotrast to other wrikle fillers, SCULPTRA provides a gradual correctio of a cotour deficiecy over several weeks. 7. Massage Durig the Ijectio Sessio. The treatmet area should be massaged i a circular fashio after every 3 ijectios to evely distribute the product. 8. Degree of Correctio. The cotour deficiecy should be uder-corrected, ever fully corrected or overcorrected (overfilled) durig ay ijectio sessio. Uder-correctio of the treatmet area allows for gradual improvemet of the cotour deficiecy as the SCULPTRA effect occurs over the miimum of three weeks betwee assessmet ad possible ext ijectio sessio. 9. Post-treatmet Care. Immediately after a SCULPTRA ijectio sessio, redess, swellig, ad/or bruisig may appear i the treatmet area. See ADVERSE EVENTS for details of the icidece ad severity of adverse evet observed immediately post-ijectio durig the cliical trial. To help SCULPTRA distribute evely i the cotour deficiecy, it is 9 importat at the ed of the treatmet sessio to maually massage i a circular fashio the treatmet area for a miimum of 2 miutes. A facial moisturizer should be used to perform the massage. It is recommeded that the patiet should massage the treated areas for five miutes, five times per day for five after the ijectio sessio to promote a atural-lookig correctio. To reduce the risk of edema ad/or bruisig after ijectio, a ice pack (avoid ay direct cotact of the ice with the ski) is applied to the treated areas. Early occurrece of subcutaeous odules at the ijectio site (withi 3 to 6 weeks after the treatmet) may be miimized by adherig to proper dilutio ad ijectio techiques (e.g., avoidig superficial ijectios or over-correctio). I additio, massagig the treatmet area to esure proper distributio of the product may also miimize the appearace of odules. Nodules usually resolve spotaeously. However, as reported i published literature, some odules may require medical treatmet such as subcisio (break-up of odules with sterile salie solutio), ad delayed occurrece of subcutaeous odules at the ijectio site (usually will maifest withi 3 to moths after the treatmet) may require treatmet such as itralesioal ijectios of corticosteroids, subcisio ad/or excisio. 10. Treat, Wait, Assess. Durig the first ijectio sessio with SCULPTRA, oly a limited correctio should be made. The cotour deficiecy should be uder-corrected, ever fully corrected or overcorrected (overfilled) durig ay ijectio sessio. Re-evaluate the patiet o sooer tha three weeks after the ijectio sessio to determie if additioal correctio is eeded. The patiet should be advised before ad after a ijectio, that typically at the ed of the ijectio sessio, it is expected to experiece some degree of swellig associated with the ijectio procedure itself. This will give the appearace of a full correctio by the ed of the ijectio sessio ad this ijectio-related swellig typically resolves i several hours to a few. For this reaso, the origial cotour deficiecy may iitially reappear, but the deficiecy is expected to gradually improve withi several weeks of SCULPTRA ijectio as the effect occurs. The patiet should be advised of the potetial eed for up to four ijectio sessios (typically three) at the first cosultatio. PATIENT INSTRUCTIONS It is recommeded that the followig iformatio is shared with patiets by the healthcare provider: To report ay adverse reactios, call saofi-avetis U.S. at Withi the first 2 hours, a ice pack (avoidig ay direct cotact of the ice with the ski) should be applied to the treatmet area to reduce swellig ad bruisig. SCULPTRA may cause redess, swellig, or bruisig whe first ijected ito the ski, typically resolvig i hours to oe week. Hematoma may also occur, typically resolvig i hours to about two weeks. Worseig or prologed symptoms or sigs should be reported to the health care provider. The origial ski depressio may iitially reappear, but the depressio should gradually improve withi several weeks as the treatmet effect of SCULPTRA occurs. The health care provider will assess the eed for additioal SCULPTRA ijectio sessios after at least three weeks. It is recommeded to massage i a circular fashio the treated areas for 5 miutes, 5 times per day for 5 followig ay ijectio sessio, accordig to the physicia s advice. Treatmet with SCULPTRA ca result i small papules i the treated area. These subcutaeous papules are typically ot visible ad asymptomatic ad may be oticed oly upo pressig o the treatmet area. However, visible odules, sometimes with redess or color chage to the ski, have bee reported. Patiets should report these evets ad ay other side effects to their health care provider. make-up may be applied a few hours post-treatmet if o complicatios are preset. Exposure of the treated area to su ad UV lamp exposure are to be avoided util ay iitial swellig ad redess has resolved. Patiets should be iformed about appropriate suscree protectio accordig to the physicia s advice. ANY SIDE EFFECTS, ADVERSE EVENTS, PRODUCT QUESTIONS OR PRODUCT COMPLAINTS SHOULD BE REPORTED TO: saofi-avetis U.S. LLC Bridgewater, NJ Prescribig Iformatio as of December Dermik Laboratories a busiess of saofi-avetis U.S. LLC Bridgewater, NJ saofi-avetis U.S. LLC Cautio: Federal (USA) law restricts this device to sale by or o the order of a licesed physicia or properly licesed practitioer. A PATIENT S GUIDE TO TREATMENT WITH SCULPTRA SCULPTRA (ijectable poly-l-lactic acid) Please review this iformatio carefully before begiig your SCULPTRA Treatmet. This guide is iteded to help you become familiar with SCULPTRA use, as well as the expected correctio, method of ijectio, post-ijectio ski care ad possible side effects. You may request additioal iformatio such as the product label that further describes SCULPTRA ad its cliical data your physicia. This iformatio is also available o This iformatio is ot meat to replace iformatio provided by your healthcare provider. You should always ask your healthcare provider about your treatmet ad care.

10 GLOSSARY : A substace that causes loss of feelig or awareess. A topical or local aesthetic is a drug that causes temporary loss of feelig i a part of the body where it is placed. Atiseptic: A aget that kills bacteria or prevets or slows growth of germs. Biocompatible: A material that does ot harm the body. Biodegradable: A material that ca be broke dow by the body. Collage: The most commo protei foud i the body. Collage is used to form a framework to support cell ad tissue. Hypersesitivity: udesirable, discomfort producig reactio; or a allergic reactio. Ijectio: Product delivery at the locatio of a hollow eedle tip beeath the surface of the ski. Immuocompetet: Has a healthy immue system Keloid formatio /Hypertrophic scarrig: A overgrowth of scar tissue at the site of a ski ijury. Keloids/hypertrophic scars may occur aroud surgical cuts, traumatic wouds, vacciatio sites, burs, or mior scratches. Hypertrophic scarrig commoly resolves durig the first year after ijury; keloid formatio most commoly does ot resolve. Lipoatrophy: Loss of fat that is ormally uder the ski. Nasolabial fold/ wrikle: Lies betwee the ose ad the corer of the mouth. Nodule: Lump uder the surface of the ski that is greater tha 5 mm, may be visible or ot visible, but ca be felt whe pressed. Palpable: Able to be touched ad felt. Papule: Lump uder the surface of the ski that is less tha 5 mm ad ot visible, but ca be felt whe pressed. Patiet label: Product iformatio for patiets Peri-orbital: Aroud the eye. Poly-L-lactic acid: A ma-made lactic acid polymer that is biocompatible ad biodegradable. Product label: Product iformatio for healthcare providers Side effect: A uwated evet caused by use of the product. Wrikle: age-related defect i the cotour of the ski surface. Wrikle Assessmet Score (WAS): a six poit photo-umeric scale for the assessmet of asolabial fold wrikles (see Figure 1). Wrikle filler: A product that is ijected uder the surface of ski to fill a space to decrease the appearace of a cosmetic facial cotour deficiecy such as facial lies, wrikles or folds. WHAT IS SCULPTRA AESTHETIC? SCULPTRA is a sterile, ijectable, biocompatible, biodegradable material that is made of very small particles of a sythetic polymer amed poly-l-lactic acid (PLLA), carboxymethylcellulose (USP), o-pyrogeic maitol (USP) ad sterile water for ijectio (USP). While the time eeded for SCULPTRA to resorb i humas is ot kow, i rabbits, particles were visible at over oe year after ijectio. WHO MIGHT BENEFIT FROM TREATMENT WITH SCULPTRA AESTHETIC? SCULPTRA AESTHETIC is iteded for use i people with healthy immue systems as oe-time treatmet regime of up to ijectio sessios that are scheduled about 3 weeks apart for correctio of shallow to deep asolabial fold cotour deficiecies ad other facial wrikles i which deep dermal grid patter (cross-hatch) ijectio techique is appropriate. SCULPTRA may provide cosmetic correctio of facial wrikles with a Wrikle Assessmet Score of 2, 3, or as show i the followig photos (Figure 1): Your healthcare provider ca help you determie if you might beefit SCULPTRA ad the optimal cosmetic correctio expected for you. I the US cliical study, optimal correctio at 9 weeks after iitial ijectio was most commoly foud to be a 0.5 to 1 poit decrease (improvemet) i WAS. WHO SHOULD NOT GET SCULPTRA AESTHETIC? (CONTRAINDICATIONS) You should ot get SCULPTRA AESTHETIC if you: Are allergic to ay igrediet of SCULPTRA AESTHETIC: poly-l-lactic acid (PLLA), carboxymethylcellulose (USP) or o-pyrogeic maitol (USP). Previously had or have risks factors for hypertrophic scarrig or keloid formatio. WHAT SHOULD I BE AWARE OF BEFORE RECEIVING SCULPTRA AESTHETIC INJECTIONS (WARNINGS AND PRECAUTIONS)? I additio to the other iformatio cotaied i this guide, you should be aware of the followig: It is ukow whether SCULPTRA may be see durig radiologic imagig of your face. If radiologic imagig of your face such as computer tomography (CT) or magetic resoace imagig (MRI) is to be performed, you should otify the physicia about the locatio of your previous SCULPTRA ijectio. HOW DOES SCULPTRA AESTHETIC WORK? Collage productio i the body decreases as you get older ad/or are exposed to the su. Wrikles are oe of the first visible sigs of this. SCULPTRA AESTHETIC is ijected ito the deep layer of the ski where collage aturally exists ad is made. SCULPTRA works by iitially fillig a wrikle with small PLLA beads. As the beads biodegrade the body may produce ew collage where SCULPTRA is ijected. SCULPTRA is ijected with multiple small ijectios usig a fie eedle i a grid patter to correct a wrikle at the asolabial fold or other facial wrikles where this ijectio techique is appropriate: 10 WHAT WERE THE RESULTS OF THE U.S. CLINICAL STUDY CONDUCTED ON SCULPTRA AESTHETIC? A U.S. study was coducted to compare the safety ad effectiveess of SCULPTRA ad a cotrol for the treatmet of facial wrikles. The treatmet cosisted of oe to four visits at three (3) week itervals durig which the 233 received treatmet with either SCULPTRA (=116) or the cotrol (=117). Subjects were followed for 13 moths after the last treatmet. Doctors graded stadardized photographs to evaluate the wrikle reductio effectiveess of both SCULPTRA ad the cotrol. Safety was evaluated by comparig the umber ad severity of side effects durig the study. Side effects are summarized i the table 1 below. TABLE 1: NUMBER OF SUBJECTS WITH INJECTION-RELATED SIDE EFFECTS OBSERVED IN SCULPTRA AESTHETIC U.S. CLINICAL STUDY SIDE EFFECTS TYPE Immediate, as recorded i subject diaries 116 Subjects N (%) Swellig 9 (81.0%) Tederess 9 (81.0%) Redess 90 (77.6%) Post-Ijectio Site Pai 82 (70.7%) Bruisig 75 (6.7%) Bleedig Site(s) 39 (33.6%) Itchig 23 (19.8%) Other 19 (16.%) DELAYED, as reported by physicias Nodules ad papules 20 (17.2%) Delayed ijectio site pai* 1 (0.9%) Average time to appearace after first ijectio: Average time of duratio: Nodules Papules Nodules Papules *oe subject reported mild ijectio site pai approximately 20 moths after first ijectio, o iformatio o outcome was available at the ed of the 25 moth extesio phase study Most side effects were mild ad resolved o their ow; oe small papule required treatmet by the healthcare provider. Five ew Sculptra-related evets were reported more tha 13 moths after first ijectio with SCULPTRA i three : 2 papules (1.9%), 1 odule (0.9%) ad 2 ijectio site pai (0.9%). Results showed that SCULPTRA had effects lastig up to 25 moths i some patiets for the treatmet of asolabial fold wrikles as compared to cotrol. Both treatmets were well tolerated. WHAT ADVERSE EVENTS HAVE BEEN REPORTED THROUGH VOLUNTARY POST- MARKETING SURVEILLANCE OF SCULPTRA AND SCULPTRA AESTHETIC USE IN AND OUTSIDE OF THE US? The most commoly reported serious adverse evets were lumps or odules at the ijectio site, delayed swolle lumps (graulomas), redess, pai, iflammatio, swellig, hypersesitivity ad itchig. The followig evets were reported more tha 5 times: Ijectio site odules mostly occurred several moths after ijectio, startig 1 2 moths to 1 moths after last Sculptra admiistratio. I some cases, the odules wet away o their ow or after treatmet with corticosteroid ijectios; other odules lasted up to 2 years. I some cases surgery was required to remove the odules. Serious delayed swolle lumps (graulomas) were reported several moths after ijectio to more tha 1 year after ijectio. These were treated with corticosteroid ijectios or surgical procedures. Some cases ivolvig the area uder the eyes (ifraorbital) or ijectio i the red area of lips (lip vermilio) required hospitalizatio. For cases where iformatio was available, the patiets were recoverig followig treatmet.