CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Adult Plaque Psoriasis. Four multicenter, randomized, double-blind, placebo-controlled trials (Trials PsO1, PsO2, PsO3, and PsO4) enrolled 2403 subjects (691 randomized to COSENTYX 300 mg, 692 to COSENTYX 150 mg, 694 to placebo, and 323 to biologic active control) 18 years of age and older with plaque psoriasis who had minimum body surface area involvement of 10%, and Psoriasis Area and Severity Index (PASI) score greater than or equal to 12, and who were candidates for phototherapy or systemic therapy.Trial PsO1 (NCT01365455) enrolled 738 subjects (245 randomized to COSENTYX 300 mg, 245 to COSENTYX 150 mg, and 248 to placebo). Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and followed by dosing every weeks. Subjects randomized to COSENTYX received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and followed by the same dose every weeks. Subjects randomized to receive placebo that were non-responders at Week 12 were then crossed over to receive COSENTYX (either 300 mg or 150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every weeks. All subjects were followed for up to 52 weeks following first administration of study treatment.Trial PsO2 (NCT01358578) enrolled 1306 subjects (327 randomized to COSENTYX 300 mg, 327 to COSENTYX 150 mg, 326 to placebo, and 323 to biologic active control). COSENTYX and placebo data are described. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and followed by dosing every weeks. Subjects randomized to COSENTYX received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and followed by the same dose every weeks. Subjects randomized to receive placebo that were non-responders at Week 12 then crossed over to receive COSENTYX (either 300 mg or 150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every weeks. All subjects were followed for up to 52 weeks following first administration of study treatment.Trial PsO3 (NCT01555125) enrolled 177 subjects (59 randomized to COSENTYX 300 mg, 59 to COSENTYX 150 mg, and 59 to placebo) and assessed safety, tolerability, and usability of COSENTYX self-administration via prefilled syringe for 12 weeks. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every weeks for up to 12 weeks total.Trial PsO4 (NCT01636687) enrolled 182 subjects (60 randomized to COSENTYX 300 mg, 61 to COSENTYX 150 mg, and 61 to placebo) and assessed safety, tolerability, and usability of COSENTYX self-administration via Sensoready pen for 12 weeks. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every weeks for up to 12 weeks total.EndpointsIn all trials, the endpoints were the proportion of subjects who achieved reduction in PASI score of at least 75% (PASI 75) from baseline to Week 12 and treatment success (clear or almost clear) on the Investigators Global Assessment modified 2011 (IGA). Other evaluated outcomes included the proportion of subjects who achieved reduction in PASI score of at least 90% (PASI 90) from baseline at Week 12, maintenance of efficacy to Week 52, and improvements in itching, pain, and scaling at Week 12 based on the Psoriasis Symptom Diary(C).The PASI is composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of psoriatic changes within the affected regions (induration, erythema and scaling). The IGA is 5-category scale, including 0 clear, 1 almost clear, 2 mild, 3 moderate or 4 severe indicating the physicians overall assessment of the psoriasis severity focusing on induration, erythema and scaling. Treatment success of clear or almost clear consisted of no signs of psoriasis or normal to pink coloration of lesions, no thickening of the plaque, and none to minimal focal scaling.Baseline CharacteristicsAcross all treatment groups the baseline PASI score ranged from 11 to 72 with median of 20 and the baseline IGA score ranged from moderate (62%) to severe (38%). Of the 2077 plaque psoriasis subjects who were included in the placebo-controlled trials, 79% were biologic-naive (have never received prior treatment with biologics) and 45% were non-biologic failures (failed to respond to prior treatment with non-biologic therapies). Of the subjects who received prior treatment with biologics, over one-third were biologic failures. Approximately 15% to 25% of trial subjects had history of psoriatic arthritis.Clinical ResponseThe results of Trials PsO1 and PsO2 are presented in Table 3.Table 3: Clinical Outcomes at Week 12 in Adults with Plaque Psoriasis in Trials PsO1 and PsO2Trial PsO1Trial PsO2COSENTYX300 mg(N 245)n (%)COSENTYX150 mg(N 245)n (%)Placebo(N 248)n (%)COSENTYX300 mg(N 327)n (%)COSENTYX150 mg(N 327)n (%)Placebo(N 326)n (%)PASI 75 response200 (82)174 (71)11 (4)249 (76)219 (67)16 (5)IGA of clear or almost clear160 (65)125 (51)6 (2)202 (62)167 (51)9 (3)The results of Trials PsO3 and PsO4 are presented in Table 4.Table 4: Clinical Outcomes at Week 12 in Adults with Plaque Psoriasis in Trials PsO3 and PsO4Trial PsO3Trial PsO4COSENTYX300 mg(N 59)n (%)COSENTYX150 mg(N 59)n (%)Placebo(N 59)n (%)COSENTYX300 mg(N 60)n (%)COSENTYX150 mg(N 61)n (%)Placebo(N 61)n (%)PASI 75 response44 (75)41 (69)0 (0)52 (87)43 (70)2 (3)IGA of clear or almost clear40 (68)31 (53)0 (0)44 (73)32 (52)0 (0)Examination of age, gender, and race subgroups did not identify differences in response to COSENTYX among these subgroups. Based on post-hoc sub-group analyses in subjects with moderate to severe psoriasis, subjects with lower body weight and lower disease severity may achieve an acceptable response with COSENTYX 150 mg.PASI 90 response at Week 12 was achieved with COSENTYX 300 mg and 150 mg compared to placebo in 59% (145/245) and 39% (95/245) versus 1% (3/248) of subjects, respectively (Trial PsO1) and 54% (175/327) and 42% (137/327) versus 2% (5/326) of subjects, respectively (Trial PsO2). Similar results were seen in Trials PsO3 and PsO4.With continued treatment over 52 weeks, subjects in Trial PsO1 who were PASI 75 responders at Week 12 maintained their responses in 81% (161/200) of the subjects treated with COSENTYX 300 mg and in 72% (126/174) of subjects treated with COSENTYX 150 mg. Trial PsO1 subjects who were clear or almost clear on the IGA at Week 12 also maintained their responses in 74% (119/160) of subjects treated with COSENTYX 300 mg and in 59% (74/125) of subjects treated with COSENTYX 150 mg. Similarly in Trial PsO2, PASI 75 responders maintained their responses in 84% (210/249) of subjects treated with COSENTYX 300 mg and in 82% (180/219) of subjects treated with COSENTYX 150 mg. Trial PsO2 subjects who were clear or almost clear on the IGA also maintained their responses in 80% (161/202) of subjects treated with COSENTYX 300 mg and in 68% (113/167) of subjects treated with COSENTYX 150 mg.Among the subjects who chose to participate (39%) in assessments of patient reported outcomes, improvements in signs and symptoms related to itching, pain, and scaling, at Week 12 compared to placebo (Trials PsO1 and PsO2) were observed using the Psoriasis Symptom Diary(C).Psoriasis Lesions of ScalpA randomized, placebo-controlled trial (Trial PsO5; NCT02267135) enrolled 102 subjects with moderate to severe psoriasis lesions of scalp, defined as having Psoriasis Scalp Severity Index (PSSI) score of greater than or equal to 12, an IGA scalp only score of or greater, and at least 30% of the scalp affected. In this trial, 62% of subjects had at least 50% of scalp surface area affected. The proportions of subjects achieving an IGA scalp only score of or (clear or almost clear) were 56.9% and 5.9% for the COSENTYX 300 mg and the placebo groups, respectively.. Trial PsO1 (NCT01365455) enrolled 738 subjects (245 randomized to COSENTYX 300 mg, 245 to COSENTYX 150 mg, and 248 to placebo). Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and followed by dosing every weeks. Subjects randomized to COSENTYX received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and followed by the same dose every weeks. Subjects randomized to receive placebo that were non-responders at Week 12 were then crossed over to receive COSENTYX (either 300 mg or 150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every weeks. All subjects were followed for up to 52 weeks following first administration of study treatment.. Trial PsO2 (NCT01358578) enrolled 1306 subjects (327 randomized to COSENTYX 300 mg, 327 to COSENTYX 150 mg, 326 to placebo, and 323 to biologic active control). COSENTYX and placebo data are described. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and followed by dosing every weeks. Subjects randomized to COSENTYX received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and followed by the same dose every weeks. Subjects randomized to receive placebo that were non-responders at Week 12 then crossed over to receive COSENTYX (either 300 mg or 150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every weeks. All subjects were followed for up to 52 weeks following first administration of study treatment.. Trial PsO3 (NCT01555125) enrolled 177 subjects (59 randomized to COSENTYX 300 mg, 59 to COSENTYX 150 mg, and 59 to placebo) and assessed safety, tolerability, and usability of COSENTYX self-administration via prefilled syringe for 12 weeks. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every weeks for up to 12 weeks total.. Trial PsO4 (NCT01636687) enrolled 182 subjects (60 randomized to COSENTYX 300 mg, 61 to COSENTYX 150 mg, and 61 to placebo) and assessed safety, tolerability, and usability of COSENTYX self-administration via Sensoready pen for 12 weeks. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every weeks for up to 12 weeks total.. 14.2 Pediatric Plaque Psoriasis. 52-week, multicenter randomized, double-blind, placebo and active-controlled trial (Trial PsO6; NCT02471144) enrolled 162 pediatric subjects years of age and older, with severe plaque psoriasis (as defined by PASI score >= 20, an IGA modified 2011 score of 4, and involving >= 10% of the body surface area) who were candidates for systemic therapy.Subjects were randomized to receive placebo, COSENTYX, or biologic active control. In the COSENTYX groups, subjects with body weight 25 kg received 75 mg, subjects with body weight 25 to 50 kg received either 75 mg or 150 mg (2 times the recommended dose), and subjects with body weight >= 50 kg received either 150 mg or 300 mg (2 times the recommended dose). Subjects in the COSENTYX and placebo groups received treatment at Weeks 0, 1, 2, 3, and followed by dosing every weeks. At Week 12, subjects randomized to placebo who were non-responders were switched to COSENTYX (dose based on body weight) and received COSENTYX at Weeks 12, 13, 14, and 15, followed by the same dose every weeks starting at Week 16.Overall, 60% of the subjects were female, 83% were Caucasian, the median body weight was 50.6 kg, and the mean age was 13.5 years with 23% of the subjects 12 years. At baseline, the median PASI score was 26 (ranged from 17 to 60), and 99% of the subjects had an IGA modified 2011 score of (severe). Approximately 43% of the subjects had prior exposure to phototherapy, 53% to conventional systemic therapy, 3% to biologics, and 9% had concomitant psoriatic arthritis.The co-primary endpoints were the proportion of subjects who achieved reduction in PASI score of at least 75% (PASI 75) from baseline to Week 12 and the proportion of subjects who achieved an IGA modified 2011 score of clear or almost clear (0 or 1) with at least 2-point improvement from baseline to Week 12. The key secondary endpoint was the proportion of subjects who achieved reduction in PASI score of at least 90% (PASI 90) from baseline to Week 12.Clinical ResponseTable presents the efficacy results at Week 12 by baseline weight strata for the approved dose.Table 5: Clinical Outcomes at Week 12 in Pediatric Subjects with Severe Plaque Psoriasis in Trial PsO6Non-responder imputation was used to handle missing values. aCOSENTYX treated subjects received 75 mg for subjects 50 kg and 150 mg for subjects >= 50 kg body weight.Body Weight 50 kgBody Weight >= 50 kgTotalCOSENTYX75 mg(N 22)n (%)Placebo (N 20)n (%)COSENTYX150 mg(N 21)n (%)Placebo (N 21)n (%)COSENTYXa (N 43)n (%)Placebo (N 41)n (%)IGA of clear or almost clear7 (32)1 (5)17 (81)1 (5)24 (56)2 (5)PASI 75 response12 (55)2 (10)18 (86)4 (19)30 (70)6 (15)PASI 90 response9 (41)1 (5)17 (81)0 (0)26 (60)1 (2). 14.3 Adult Psoriatic Arthritis. The safety and efficacy of COSENTYX were assessed in 1999 patients, in randomized, double-blind, placebo-controlled studies (PsA1, PsA2 and PsA3) in adult patients, age 18 years and older with active psoriatic arthritis (greater than or equal to swollen and greater than or equal to tender joints) despite non-steroidal anti-inflammatory drug (NSAID), corticosteroid or disease modifying anti-rheumatic drug (DMARD) therapy. Patients in these studies had diagnosis of PsA of at least years across all studies. At baseline, over 61% and 42% of the patients had enthesitis and dactylitis, respectively. Overall, 31% of patients discontinued previous treatment with anti-TNF agents due to either lack of efficacy or intolerance. In addition, approximately 53% of patients from both studies had concomitant methotrexate (MTX) use. Patients with different subtypes of PsA were enrolled, including polyarticular arthritis with no evidence of rheumatoid nodules (80%), asymmetric peripheral arthritis (63%), distal interphalangeal involvement (58%), spondylitis with peripheral arthritis (20%) and arthritis mutilans (7%).PsA1 Study (NCT 01752634) evaluated 397 patients, who were treated with COSENTYX 75 mg, 150 mg or 300 mg subcutaneous treatment at Weeks 0, 1, 2, and 4, followed by the same dose every weeks. Patients receiving placebo were re-randomized to receive COSENTYX (either 150 mg or 300 mg every weeks) at Week 16 or Week 24 based on responder status. The primary endpoint was the percentage of patients achieving an ACR20 response at Week 24.PsA2 Study (NCT 01392326) evaluated 606 patients, who were treated with secukinumab 10 mg/kg, intravenous treatment (or placebo) at Weeks 0, 2, and 4, followed by either 75 mg or 150 mg subcutaneous COSENTYX treatment (or placebo) every weeks. Patients receiving placebo were re-randomized to receive COSENTYX (either 75 mg or 150 mg every weeks) at Week 16 or Week 24 based on responder status.PsA3 Study (NCT 02404350) evaluated 996 patients, who were treated with COSENTYX 150 mg or 300 mg subcutaneous treatment at Weeks 0, 1, 2, 3, and followed by the same dose every weeks, or once every weeks of COSENTYX 150 mg. Patients treated with placebo received COSENTYX, either 150 mg or 300 mg, subcutaneous, per baseline randomization, at Week 16 or Week 24 based upon responder status. The primary endpoint was ACR20 response at Week 16 with the key secondary endpoint the change from baseline in modified Total Sharp Score (mTSS) at Week 24.Clinical ResponseIn PsA1, patients treated with 150 mg or 300 mg COSENTYX demonstrated greater clinical response, including ACR20, ACR50, and ACR70 compared to placebo at Week 24 (Table 6). Responses were similar in patients regardless of concomitant methotrexate treatment. Responses were seen regardless of prior anti-TNF exposure.In patients with coexistent plaque psoriasis receiving COSENTYX (n 99), the skin lesions of psoriasis improved with treatment, relative to placebo, as measured by the Psoriasis Area Severity Index (PASI).Table 6: Responsesa in PsA1 Study at Week 16 and Week 24aPatients who met escape criteria (less than 20% improvement in tender or swollen joint counts) at Week 16 were considered non-responders.COSENTYXCOSENTYXPlaceboDifference from Placebo (95% CI)150 mg(N 100)300 mg(N 100)(N 98)COSENTYX150 mgCOSENTYX300 mgACR20 responseWeek 16 (%)60571842(30, 54)38(26, 51)Week 24 (%)51541536(24, 48)39(27, 51)ACR50 responseWeek 16 (%)3735631(21, 42)28(18, 39)Week 24 (%)3535728(18, 38)28(17, 38)ACR70 responseWeek 16 (%)1715215(7, 23)13(5, 20)Week 24 (%)2120120(12, 28)19(11, 27)The percentage of patients achieving ACR20 response by visit is shown in Figure 1. Patients on placebo who received COSENTYX without loading regimen achieved similar ACR20 responses over time (data not shown).Figure 1: Percent of Patients Achieving ACR 20 Responsea in PsA1 Study Through Week 24aPatients who met escape criteria (less than 20% improvement in tender or swollen joint counts) at Week 16 were considered non-responders.The improvements in the components of the ACR response criteria are shown in Table 7.Table 7: Mean Change From Baseline in ACR Components at Week 16a (PsA1 Study)aWeek 16 rather than Week 24 data are displayed to provide comparison between arms prior to placebo escape to COSENTYX.bMean Change based upon observed data.COSENTYX150 mg(N 100)COSENTYX300 mg(N 100)Placebo(N 98)No. of Swollen JointsBaseline12.011.212.1Mean change at Week 16-4.86-5.83-3.22Number of Tender JointsBaseline24.120.223.5Mean change at Week 16-10.70-10.01-1.77Patients Assessment of PainBaseline58.957.755.4Mean change at Week 16-22.91-23.97-7.98Patient Global AssessmentBaseline62.060.757.6Mean change at Week 16-25.47-25.40-8.25Physician Global AssessmentBaseline56.755.055.0Mean change at Week 16-29.24-34.71-14.95Disability Index (HAQ)Baseline1.22001.28281.1684Mean change at Week 16-0.45-0.55-0.23CRP (mg/L)Baseline14.1510.887.87Mean Change at Week 16b -8.41-7.210.79Improvements in enthesitis and dactylitis scores were observed in each COSENTYX group compared to placebo at Week 24.Radiographic ResponseIn PsA3 Study, inhibition of progression of structural damage was assessed radiographically and expressed by the modified mTSS and its components, the Erosion Score (ES) and Joint Space Narrowing Score (JSN), at Week 24 compared to baseline. Radiographs of hands, wrists, and feet were obtained at baseline, Week 16 and/or Week 24 and scored independently by at least two readers who were blinded to treatment group and visit number. COSENTYX 150 mg without load, 150 mg with load and 300 mg with load treatment significantly inhibited progression of peripheral joint damage compared with placebo treatment as measured by change from baseline in mTSS at Week 24. The percentage of patients with no disease progression (defined as change from baseline in mTSS of less than or equal to 0.0) from randomization to Week 24 was 75.7%, 70.9%, and 76.5% for COSENTYX 150 mg without load, 150 mg, 300 mg, respectively versus 68.2% for placebo.Table 8: Rate of Change per 24 Weeks in Modified Total Sharp ScoreResults from linear mixed effects model that excluded data after escape for placebo subjects who received escape therapy at Week 16. The model assumes approximately linear progression over time and estimates difference in rates (slopes) of progression over 24 weeks to compare treatment arms.TreatmentNRate of Change per 24 weeksDifference from Placebo(95% CI)COSENTYX 150 mg without load 210-0.10-0.61 (-0.95, -0.26)COSENTYX 150 mg with load2130.14-0.37 (-0.71, -0.03)COSENTYX 300 mg with load2170.03-0.48 (-0.82, -0.14)Placebo2960.51--Physical FunctionImprovement in physical function as assessed by Health Assessment Questionnaire-Disability Index (HAQ-DI) demonstrated that the proportion of patients who achieved at least -0.3 improvement in HAQ-DI score from baseline was greater in the COSENTYX 150 mg and 300 mg groups compared to placebo at Week 16 and 24. At Week 16 in PsA1 study, estimated mean change from baseline was -0.23 in the placebo group compared with -0.45 in the COSENTYX 150 mg group and -0.55 in the COSENTYX 300 mg group.. Figure 1: Percent of Patients Achieving ACR 20 Responsea in PsA1 Study Through Week 24. 14.4 Ankylosing Spondylitis. The safety and efficacy of COSENTYX were assessed in 816 patients in three randomized, double-blind, placebo-controlled studies (AS1, AS2, and AS3) in adult patients 18 years of age and older with active ankylosing spondylitis. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) greater or equal to despite non-steroidal anti-inflammatory drug (NSAID), corticosteroid or disease modifying anti-rheumatic drug (DMARD) therapy. At baseline, approximately 13% and 25% used concomitant methotrexate or sulfasalazine, respectively. Overall, 29% of patients discontinued previous treatment with anti-TNF agents due to either lack of efficacy or intolerance.AS1 Study (NCT01649375) evaluated 219 patients, who were treated with COSENTYX 75 mg or 150 mg subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every weeks. At Week 16, patients receiving placebo were re-randomized to either COSENTYX 75 mg or 150 mg every weeks. The primary endpoint was the percentage of patients achieving an ASAS20 response at Week 16.AS2 Study (NCT01358175) evaluated 371 patients, who were treated with secukinumab 10 mg/kg intravenous treatment at Weeks 0, 2, and (for both treatment arms) or placebo, followed by either 75 mg or 150 mg subcutaneous COSENTYX treatment every weeks or placebo. Patients receiving placebo were re-randomized to receive COSENTYX (either 75 mg or 150 mg every weeks) at Week 16 or Week 24 based on responder status.AS3 Study (NCT02008916) evaluated 226 patients, who were treated with secukinumab 10 mg/kg intravenous treatment at Weeks 0, 2, and (for both treatment arms) or placebo, followed by either 150 mg or 300 mg subcutaneous COSENTYX treatment every weeks or placebo. Patients receiving placebo were re-randomized to receive COSENTYX (either 150 mg or 300 mg every weeks) at Week 16. The primary endpoint was the percentage of patients achieving an ASAS20 response at Week 16. Patients were blinded to the treatment regimen up to Week 52, and the study continued to Week 156.Clinical ResponseIn AS1, patients treated with 150 mg COSENTYX demonstrated greater improvements in ASAS20 and ASAS40 responses compared to placebo at Week 16 (Table 9). Responses were similar in patients regardless of concomitant therapies.Table 9: ASAS20 and ASAS40 Responses in All AS Patients at Week 16 in Study AS1COSENTYX150 mg(n 72)Placebo (n 74)Difference from placebo(95% CI)ASAS20 response, %612833(18, 48)ASAS40 response, %361125(12, 38)The improvements in the main components of the ASAS20 response criteria and other measures of disease activity are shown in Table 10.Table 10: ASAS20 Components and Other Measures of Disease Activity at Week 16 (AS1 Study)Percent of subjects with at least 20% and 10 unit improvement measured on Visual Analog Scale (VAS) with = none, 100 severeBath Ankylosing Spondylitis Functional Index.Inflammation is the mean of two patient-reported stiffness self-assessment in BASDAI.Bath Ankylosing Spondylitis Disease Activity Index.Bath Ankylosing Spondylitis Metrology Index.High sensitivity C-reactive protein mean change based upon observed data.COSENTYX150 mg(N 72)Placebo (N 74)BaselineWeek 16change from baselineBaselineWeek 16change from baselineASAS20 Response criteria -Patient Global Assessment of Disease Activity (0-100 mm)1 67.5-27.770.5-12.9 -Total spinal pain (0-100 mm)66.2-28.569.2-10.9 -BASFI (0-10)2 6.2-2.26.1-0.7 -Inflammation (0-10)3 6.5-2.56.5-0.8 BASDAI Score46.6-2.26.8-0.9 BASMI53.6-0.513.9-0.22 hsCRP6 (mg/L) Mean Change at Week 1627.0-17.215.90.8The percent of patients achieving ASAS20 responses by visit is shown in Figure 2. Patients on placebo who received COSENTYX without loading regimen achieved similar ASAS20 responses over time (data not shown).Figure 2: ASAS20 Responses in All AS1 Study Patients Over Time Up to Week 16In AS3 Study, patients treated with COSENTYX (150 mg and 300 mg) demonstrated improved signs and symptoms, and had comparable efficacy responses, regardless of dose, that were superior to placebo at Week 16 for the primary and most secondary endpoints. At Week 16, the ASAS20 and ASAS40 responses were 58.1% and 40.5% for 150 mg and 60.5% and 42.1% for 300 mg, respectively. The percent of patients achieving ASAS20 responses by visit is shown in Figure 3.Figure 3: ASAS20 Responses in All AS3 Study Patients Over Time Up to Week 16COSENTYX treated patients showed improvement compared to placebo-treated patients in health-related quality of life as assessed by ASQoL at Week 16.. Percent of subjects with at least 20% and 10 unit improvement measured on Visual Analog Scale (VAS) with = none, 100 severe. Bath Ankylosing Spondylitis Functional Index.. Inflammation is the mean of two patient-reported stiffness self-assessment in BASDAI.. Bath Ankylosing Spondylitis Disease Activity Index.. Bath Ankylosing Spondylitis Metrology Index.. High sensitivity C-reactive protein mean change based upon observed data.. Figure 2: ASAS20 Responses in All AS1 Study Patients Over Time Up to Week 16. Figure 3: ASAS20 Responses in All AS3 Study Patients Over Time Up to Week 16. 14.5 Non-Radiographic Axial Spondyloarthritis. The safety and efficacy of COSENTYX were assessed in 555 patients in one randomized, double-blind, placebo-controlled Phase study (nr-axSpA1, NCT02696031) in adult patients 18 years of age and older with active non-radiographic axial spondyloarthritis. Patients met ASAS criteria for axial spondyloarthritis and had active disease as defined by BASDAI greater or equal to 4, Visual Analogue Scale (VAS) for total back pain greater or equal to 40 (on scale of 0-100 mm) despite NSAID therapy and no evidence of radiographic changes in the sacroiliac joints that would meet the modified New York criteria for AS. Patients also had to have objective signs of inflammation with C-reactive protein (CRP) level above the upper limit of normal and/or evidence of sacroiliitis on Magnetic Resonance Imaging (MRI). Approximately 10% and 15% of patients used concomitant methotrexate or sulfasalazine, respectively. Overall, 10% of patients had received previous treatment with anti-TNF agents and discontinued these due to either lack of efficacy or intolerance.Patients were treated with COSENTYX 150 mg subcutaneous treatment with load (Weeks 0, 1, 2, 3, and 4) or without load (Weeks and 4) followed by the same dose every weeks or placebo. In the double-blind period, patients (n 555) received either placebo or COSENTYX for 52 weeks. Starting Week 16, dose adjustment or addition of concomitant NSAIDs and DMARDs was permitted. Starting at Week 20, patients were allowed to switch to open-label COSENTYX 150 mg monthly or other biologic at the discretion of the investigator and patient. The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society (ASAS40) at Week 52.Clinical ResponseIn nr-axSpA1 Study, treatment with COSENTYX 150 mg resulted in significant improvements in the measure of disease activity compared to placebo at Week 16 and Week 52 (Table 11).Table 11: Clinical Response in nr-axSpA1 Study at Week 16 and Week 52 Difference in proportions with 95% CI based on normal approximation.Number of subjects with ASAS40 response (%)COSENTYX150 mg without load(n 184)COSENTYX150 mg with load(n 185)Difference from Placebo (95% CI)Placebo(n 186)COSENTYX150 mgwithout loadCOSENTYX150 mgwith loadWeek 1675 (41)74 (40)52 (28)13 (3, 22)12 (2, 22)Week 5270 (38)62 (34)36 (19)19 (10, 28)14 (5, 23)The results of the main components of the ASAS40 response criteria are shown in Table 12.Table 12: Main Components of the ASAS40 Response Criteria and Other Measures of Disease Activity in nr-axSpA Patients at Baseline and Week 16 in nr-axSpA1 StudyCOSENTYX150 mg without load(N 184)COSENTYX150 mg with load(N 185)Placebo (N 186)BaselineWeek 16change from baselineBaselineWeek 16change from baselineBaselineWeek 16change from baselineASAS40 Response criteria -Patient Global Assessment of Disease Activity (0-100 mm) 71.0-26.272.6-24.168.8-13.8 -Total back pain (0-100 mm) 72.0-25.573.3-25.070.9-15.6 -BASFI (0-10) 5.9-1.66.2-1.85.9-1.0 -Inflammation (0-10) 6.8-2.87.2-2.86.6-1.7hsCRP (mg/L) Mean Change at Week 169.8-4.713.4-7.99.2-2.4BASDAI (0-10)6.9-2.47.1-2.46.8-1.5 -Spinal Pain7.6-3.07.8-3.07.5-2.0 -Peripheral pain and swelling (0-10)6.6-2.46.3-2.36.1-1.6BASMI2.8-0.32.9-0.32.8-0.1The percentage of patients achieving an ASAS40 response by visit is shown in Figure 4.Figure 4: ASAS40 Responses in nr-axSpA1 Study Over Time up to Week 16Health Related Quality of LifeCOSENTYX treated patients showed improvement in both load and without load arms compared to placebo-treated patients at Week 16 in health-related quality of life as measured by ASQoL (LS mean change: Week 16: -3.5 and -3.6 vs -1.8, respectively).. Figure 4: ASAS40 Responses in nr-axSpA1 Study Over Time up to Week 16. 14.6 Juvenile Psoriatic Arthritis and Enthesitis-Related Arthritis. The efficacy and safety of secukinumab were assessed in 86 patients in two year, 3-part, double-blind, placebo-controlled, event-driven, randomized, Phase study (NCT03031782) in patients to 18 years of age with active ERA or JPsA as diagnosed based on modified International League of Associations for Rheumatology (ILAR) Juvenile Idiopathic Arthritis (JIA) classification criteria. The study consisted of an open-label portion (Part 1) followed by randomized withdrawal (Part 2) followed by open-label treatment (Part 3). The JIA patient subtypes at study entry were: 60.5% ERA and 39.5% JPsA. In the study 67.6% of patients with JPsA, and 63.5% of patients with ERA, were treated concomitantly with MTX. Patients were given dose of 75 mg if weighing 50 kg, or 150 mg if weighing >= 50 kg.The primary endpoint was time to flare in Part 2. Disease flare was defined as >= 30% worsening in at least three of the six JIA ACR response criteria and >= 30% improvement in not more than one of the six JIA ACR response criteria and minimum of two active joints.In open-label Part 1, all patients received secukinumab until Week 12. Patients classified as responders (achieving JIA ACR30 response) at Week 12 entered into the Part double-blind phase and were randomized 1:1 to continue treatment with secukinumab or begin treatment with placebo. Similar responses were seen in each JIA subtype (JPsA and ERA). The JIA ACR 30, 50, 70 and 90 responses for patients with JPsA and ERA at Week 12 are presented below in Table 13.Table 13: JIA ACR 30, 50, 70 and 90 Responses at Week 12Number of subjects with response (%)JIA ACR 30JIA ACR 50JIA ACR 70JIA ACR 90JPsA (N 34)31 (91)31 (91)24 (71)16 (47)ERA (N 52)44 (85)41 (79)34 (65)17 (33)Juvenile Psoriatic ArthritisDuring Part 2, total of 11 JPsA patients in the placebo group experienced flare event compared with JPsA patients in the secukinumab group. The risk of flare was reduced by 85% for patients on secukinumab compared with patients on placebo (Hazard Ratio 0.15, 95% CI: 0.04 to 0.56) (Figure 5).Figure 5: Kaplan-Meier Estimates of the Time to Disease Flare in Part for JPsA PatientsEnthesitis-Related ArthritisDuring Part 2, total of 10 ERA patients in the placebo group experienced flare event compared with ERA patients in the secukinumab group. The risk of flare was reduced by 53% for patients on secukinumab compared with patients on placebo (Hazard Ratio 0.47, 95% CI: 0.17 to 1.32) (Figure 6). Supplementary analyses provided confirmatory evidence of the treatment effect in ERA.Figure 6: Kaplan-Meier Estimates of the Time to Disease Flare in Part for ERA Patients. Figure 5: Kaplan-Meier Estimates of the Time to Disease Flare in Part for JPsA Patients. Figure 6: Kaplan-Meier Estimates of the Time to Disease Flare in Part for ERA Patients.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).InfectionsInform patients that COSENTYX may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the doctor and contacting their doctor if they develop any symptoms of infection [see Warnings and Precautions (5.1)].HypersensitivityAdvise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.4)].Risk of Hypersensitivity in Latex-Sensitive IndividualsAdvise latex-sensitive patients that the removal caps of the COSENTYX Sensoready pen and the COSENTYX mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals [see Warnings and Precautions (5.5)].ImmunizationAdvise patients that vaccination with live vaccines is not recommended during COSENTYX treatment. Instruct patients to inform the healthcare practitioner that they are taking COSENTYX prior to potential vaccination [see Warnings and Precautions (5.6)].Instructions on Injection TechniqueIf patient or caregiver is to administer COSENTYX using the Sensoready pen or the prefilled syringe, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX [see Dosage and Administration (2.6), Medication Guide and Instructions for Use].For pediatric patients, inform patients and caregivers that pediatric patients should not self-administer COSENTYX using the pre-filled syringe or the Sensoready pen.Instruct patients or caregivers in the technique of proper syringe and needle disposal, and advise them not to reuse these texts. Instruct patients to inject the full amount of COSENTYX according to the directions provided in the Medication Guide and Instructions for Use.Manufactured by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936US License Number 1244(C) NovartisT2021-162.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions are discussed in greater detail elsewhere in the labeling:Infections [see Warnings and Precautions (5.1)] Inflammatory Bowel Disease [see Warnings and Precautions (5.3)] Hypersensitivity Reactions [see Warnings and Precautions (5.4)] Infections [see Warnings and Precautions (5.1)] Inflammatory Bowel Disease [see Warnings and Precautions (5.3)] Hypersensitivity Reactions [see Warnings and Precautions (5.4)] Most common adverse reactions (> 1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.Adult Plaque PsoriasisA total of 3430 plaque psoriasis subjects were treated with COSENTYX in controlled and uncontrolled clinical trials. Of these, 1641 subjects were exposed for at least year.Four placebo-controlled Phase trials in plaque psoriasis subjects were pooled to evaluate the safety of COSENTYX in comparison to placebo up to 12 weeks after treatment initiation, in Trials PsO1, PsO2, PsO3, and PsO4. In total, 2077 subjects were evaluated (691 to COSENTYX 300 mg group, 692 to COSENTYX 150 mg group, and 694 to placebo group). Subjects randomized to COSENTYX received 300 mg or 150 mg doses subcutaneously at Weeks 0, 1, 2, 3, and followed by the same dose every weeks [see Clinical Studies (14)].Table summarizes the adverse reactions that occurred at rate of at least 1% and at higher rate in the COSENTYX groups than the placebo group during the 12-week placebo-controlled period of the placebo-controlled trials.Table 2: Adverse Reactions Reported by Greater Than 1% of Subjects With Plaque Psoriasis Through Week 12 in Trials PsO1, PsO2, PsO3, and PsO4COSENTYXAdverse Reactions300 mg(N 691)n (%)150 mg(N 692)n (%)Placebo(N 694)n (%)Nasopharyngitis79 (11.4)85 (12.3)60 (8.6)Diarrhea28 (4.1)18 (2.6)10 (1.4)Upper respiratory tract infection17 (2.5)22 (3.2)5 (0.7)Rhinitis10 (1.4)10 (1.4)5 (0.7)Oral herpes9 (1.3)1 (0.1)2 (0.3)Pharyngitis8 (1.2)7 (1.0)0 (0)Urticaria4 (0.6)8 (1.2)1 (0.1)Rhinorrhea8 (1.2)2 (0.3)1 (0.1)Adverse reactions that occurred at rates less than 1% in the placebo-controlled period of Trials PsO1, PsO2, PsO3, and PsO4 through Week 12 included: sinusitis, tinea pedis, conjunctivitis, tonsillitis, oral candidiasis, impetigo, otitis media, otitis externa, inflammatory bowel disease, increased liver transaminases, and neutropenia.InfectionsIn the placebo-controlled period of the clinical trials in plaque psoriasis (a total of 1382 subjects treated with COSENTYX and 694 subjects treated with placebo up to 12 weeks), infections were reported in 28.7% of subjects treated with COSENTYX compared with 18.9% of subjects treated with placebo. Serious infections occurred in 0.14% of subjects treated with COSENTYX and in 0.3% of subjects treated with placebo.Over the entire treatment period (a total of 3430 plaque psoriasis subjects treated with COSENTYX for up to 52 weeks for the majority of subjects), infections were reported in 47.5% of subjects treated with COSENTYX (0.9 per patient-year of follow-up). Serious infections were reported in 1.2% of subjects treated with COSENTYX (0.015 per patient-year of follow-up).Phase data showed an increasing trend for some types of infection with increasing serum concentration of secukinumab. Candida infections, herpes viral infections, staphylococcal skin infections, and infections requiring treatment increased as serum concentration of secukinumab increased.In the psoriasis open-label extension of Trials PsO1 and PsO2 (median follow-up of 3.9 years), representing 3582 subject-years of exposure, 74% of COSENTYX treated subjects reported infections (55 per 100 patient-years). Serious infections were reported in 4.5% of subjects (1.4 per 100 patient-years). Sepsis was reported in subjects (0.2 per 100 patient-years).Neutropenia was observed in controlled portion of clinical trials. Most cases of secukinumab-associated neutropenia were transient and reversible. No serious infections were associated with cases of neutropenia.In the open-label extension of Trials PsO1 and PsO2, neutropenia (ANC 1 x109/L) was reported in 1% of COSENTYX treated subjects (0.3 per 100 patient-years). Some cases of serious infections were associated with neutropenia; however the causal relationship was not established.Inflammatory Bowel DiseaseCases of inflammatory bowel disease, in some cases serious, were observed in clinical trials with COSENTYX. In the plaque psoriasis program, with 3430 subjects exposed to COSENTYX over the entire treatment period for up to 52 weeks (2725 patient-years), there were cases (0.11 per 100 patient-years) of exacerbation of Crohns disease, cases (0.08 per 100 patient-years) of exacerbation of ulcerative colitis, and cases (0.08 per 100 patient-years) of new onset ulcerative colitis. There were no cases in placebo subjects (N 793; 176 patient-years) during the 12-week placebo-controlled period.One case of exacerbation of Crohns disease was reported in open-labeled portions of clinical trials in plaque psoriasis.Hypersensitivity ReactionsAnaphylaxis and cases of urticaria occurred in COSENTYX treated subjects in clinical trials [see Warnings and Precautions (5.4)].Pediatric Plaque PsoriasisThe safety of COSENTYX was assessed in two Phase trials in pediatric subjects with plaque psoriasis.The first was randomized, double-blind, placebo and active-controlled, 236-week trial (Trial PsO6) that enrolled 162 pediatric subjects years of age and older, with severe plaque psoriasis (defined by PASI score >= 20, an IGA modified 2011 score of 4, and involving >= 10% of the body surface area) who were candidates for systemic therapy. The 162 subjects were randomized to receive placebo, biologic active control, or COSENTYX. In the COSENTYX groups, subjects with body weight 25 kg received 75 mg, subjects with body weight 25 to 50 kg received either 75 mg or 150 mg (2 times the recommended dose), and subjects with body weight >= 50 kg received either 150 mg or 300 mg (2 times the recommended dose).The second trial was randomized, open-label, 208-week trial (Trial PsO7; NCT03668613) of 84 subjects years of age and older with moderate to severe plaque psoriasis (defined by PASI score >= 12, IGA mod 2011 score of >= 3, and BSA involvement of >= 10% at randomization) who were randomized into two COSENTYX arms [Arm 1: 75 mg for body weight (BW) 50 kg or 150 mg for >= 50 kg and Arm 2: 75 mg for BW 25 kg, 150 mg for BW >= 25 kg and 50 kg, or 300 mg for BW >= 50 kg].The safety profile reported in these trials was consistent with the safety profile reported in adult plaque psoriasis trials.InfectionsOne case of methicillin-resistant Staphylococcus aureus (MRSA) toxic shock syndrome (TSS) was reported in COSENTYX treated subject during the placebo-controlled period. In the pediatric safety pool, which includes all subjects who took at least one dose of COSENTYX during the treatment periods [198 subjects (287 patient years)], 22 (11%) subjects reported >= CTCAE Grade neutropenia (>=1,000 to 1,500 cells/mm3) with 57% of subjects followed for one year or more and 30% of subjects followed for two years or more. During the placebo-controlled period which included total of 80 subjects treated with secukinumab and 41 subjects treated with placebo up to 12 weeks, >= CTCAE Grade neutropenia was reported in (4%) of the subjects treated with secukinumab compared with no subjects treated with placebo. No serious infections were associated with cases of neutropenia.Adult Psoriatic ArthritisCOSENTYX was studied in two placebo-controlled PsA trials with 1003 patients (703 patients on COSENTYX and 300 patients on placebo). Of the 703 patients who received COSENTYX, 299 patients received subcutaneous loading dose of COSENTYX (PsA1) and 404 patients received an intravenous loading dose of secukinumab (PsA2) followed by COSENTYX administered by subcutaneous injection every four weeks. During the 16-week placebo-controlled period of the trials in patients with PsA, the overall proportion of patients with adverse events was similar in the secukinumab and placebo-treatment groups (59% and 58%, respectively). The adverse events that occurred at proportion of at least 2% and at higher proportion in the COSENTYX groups than the placebo groups during the 16-week placebo-controlled period were nasopharyngitis, upper respiratory tract infection, headache, nausea, and hypercholesterolemia. The safety profile observed in patients with PsA treated with COSENTYX is consistent with the safety profile in psoriasis.Similar to the clinical trials in patients with psoriasis, there was an increased proportion of patients with infections in the COSENTYX groups (29%) compared to placebo group (26%).There were cases of Crohns disease and ulcerative colitis that include patients who experienced either exacerbations or the development of new disease. There were three cases of inflammatory bowel disease, of which two patients received secukinumab and one received placebo.Ankylosing SpondylitisCOSENTYX was studied in two placebo-controlled AS trials with 590 patients (394 patients on COSENTYX and 196 patients on placebo). Of the 394 patients who received COSENTYX, 145 patients received subcutaneous load of COSENTYX (study AS1), and 249 received an intravenous loading dose of secukinumab (study AS2) followed by COSENTYX administered by subcutaneous injection every four weeks. During the 16-week placebo-controlled period of the trials in patients with AS, the overall proportion of patients with adverse events was higher in the secukinumab groups than the placebo-treatment groups (66% and 59%, respectively). The adverse events that occurred at proportion of at least 2% and at higher proportion in the COSENTYX groups than the placebo groups during the 16-week placebo-controlled period were nasopharyngitis, nausea, and upper respiratory tract infection. The safety profile observed in patients with ankylosing spondylitis treated with COSENTYX is consistent with the safety profile in psoriasis. In third controlled study of AS (study AS3), the safety profile of the 300 mg dose of COSENTYX was consistent with the safety profile of the 150 mg dose of COSENTYX.Similar to clinical trials in patients with psoriasis, there was an increased proportion of patients with infections in the COSENTYX groups (31%) compared to the placebo group (18%).In the original AS program, with 571 patients exposed to COSENTYX there were cases of inflammatory bowel disease during the entire treatment period [5 Crohns (0.7 per 100 patient-years) and ulcerative colitis (0.4 per 100 patient-years)]. During the placebo-controlled 16-week period, there were Crohns disease exacerbations and new onset ulcerative colitis case that was serious adverse event in patients treated with COSENTYX compared to none of the patients treated with placebo. During the remainder of the study when all patients received COSENTYX, patient developed Crohns disease, patients had Crohns exacerbations, patient developed ulcerative colitis, and patient had an ulcerative colitis exacerbation.Non-Radiographic Axial SpondyloarthritisCOSENTYX was studied in one randomized, double-blind, placebo-controlled nr-axSpA trial with 555 patients (185 patients on with load COSENTYX, 184 patients on without load COSENTYX and 186 patients on placebo). The safety profile for patients with nr-axSpA treated with COSENTYX was overall similar to the safety profile seen in patients with AS and other previous experience with COSENTYX. Patients in nr-axSpA1 study who received the loading dosing regimen compared to those without the loading regimen, had higher incidence of infections and infestations (92 per 100 patient-years vs 72 per 100 patient years), including nasopharyngitis, upper respiratory tract infection and urinary tract infection, and gastrointestinal disorders (27 per 100 patient-years vs 22 per 100 patient-years), including gastritis, lower abdominal pain, colitis, diarrhea, and hematochezia.Juvenile Psoriatic Arthritis and Enthesitis-Related ArthritisCOSENTYX was studied in one double-blind, placebo-controlled, event-driven, randomized trial in 86 pediatric patients aged to 18 years old with Juvenile Psoriatic Arthritis (JPsA) and ERA. The safety profile reported in this study was consistent with the safety profile of secukinumab.. 6.2 Immunogenicity. As with all therapeutic proteins, there is the potential for immunogenicity. The immunogenicity of COSENTYX was evaluated using an electrochemiluminescence-based bridging immunoassay. Less than 1% of subjects treated with COSENTYX developed antibodies to secukinumab in up to 52 weeks of treatment. However, this assay has limitations in detecting anti-secukinumab antibodies in the presence of secukinumab; therefore, the incidence of antibody development might not have been reliably determined. Of the subjects who developed antidrug antibodies, approximately one-half had antibodies that were classified as neutralizing. Neutralizing antibodies were not associated with loss of efficacy. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to COSENTYX with the incidences of antibodies to other products may be misleading.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of COSENTYX. Some published literature suggests that IL-17A directly promotes cancer cell invasion in vitro, whereas other reports indicate IL-17A promotes T-cell mediated tumor rejection. Depletion of IL-17A with neutralizing antibody inhibited tumor development in mice. The relevance of experimental findings in mouse models for malignancy risk in humans is unknown.No effects on fertility were observed in male and female mice that were administered murine analog of secukinumab at subcutaneous doses up to 150 mg/kg once weekly prior to and during the mating period.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Secukinumab is human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.. 12.2 Pharmacodynamics. Elevated levels of IL-17A are found in psoriatic plaques. Treatment with COSENTYX may reduce epidermal neutrophils and IL-17A levels in psoriatic plaques. Serum levels of total IL-17A (free and secukinumab-bound IL-17A) measured at Week and Week 12 were increased following secukinumab treatment. These pharmacodynamic activities are based on small exploratory studies. The relationship between these pharmacodynamic activities and the mechanism(s) by which secukinumab exerts its clinical effects is unknown.Increased numbers of IL-17A producing lymphocytes and innate immune cells and increased levels of IL-17A have been found in the blood of patients with PsA and AS. Increased numbers of IL-17A producing lymphocytes have also been found in patients with nr-axSpA.Immune Response to Non-Live Vaccines During TreatmentHealthy individuals who received single 150 mg dose of COSENTYX weeks prior to vaccination with non-U.S. approved group meningococcal polysaccharide conjugate vaccine and non-U.S. approved inactivated seasonal influenza vaccine had similar antibody responses compared to individuals who did not receive COSENTYX prior to vaccination. The clinical effectiveness of meningococcal and influenza vaccines has not been assessed in patients undergoing treatment with COSENTYX [see Warnings and Precautions (5.6)].. 12.3 Pharmacokinetics. The pharmacokinetic (PK) properties of secukinumab observed in PsA, AS and nr-axSpA patients were similar to the PK properties displayed in plaque psoriasis patients.AbsorptionFollowing single subcutaneous dose of either 150 mg (one-half the recommended dose) or 300 mg in plaque psoriasis subjects, secukinumab reached peak mean (+- SD) serum concentrations (Cmax) of 13.7 +- 4.8 mcg/mL and 27.3 +- 9.5 mcg/mL, respectively, by approximately days post dose.Following multiple subcutaneous doses of secukinumab, the mean (+- SD) serum trough concentrations of secukinumab ranged from 22.8 +- 10.2 mcg/mL (150 mg) to 45.4 +- 21.2 mcg/mL (300 mg) at Week 12. At the 300 mg dose at Week and Week 12, the mean trough concentrations resulted from the Sensoready pen were 23% to 30% higher than those from the lyophilized powder and 23% to 26% higher than those from the prefilled syringe based on cross-study comparisons.Steady-state concentrations of secukinumab were achieved by Week 24 following the every 4-week dosing regimens. The mean (+- SD) steady-state trough concentrations ranged from 16.7 +- 8.2 mcg/mL (150 mg) to 34.4 +- 16.6 mcg/mL (300 mg).In healthy subjects and subjects with plaque psoriasis, secukinumab bioavailability ranged from 55% to 77% following subcutaneous dose of 150 mg (one-half the recommended dose) or 300 mg.DistributionThe mean volume of distribution during the terminal phase (Vz) following single intravenous administration ranged from 7.10 to 8.60 in plaque psoriasis subjects. Intravenous use is not recommended [see Dosage and Administration (2)].Secukinumab concentrations in interstitial fluid in lesional and non-lesional skin of plaque psoriasis subjects ranged from 27% to 40% of those in serum at and weeks after single subcutaneous dose of secukinumab 300 mg.EliminationMetabolismThe metabolic pathway of secukinumab has not been characterized. As human IgG1 monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.ExcretionThe mean systemic clearance (CL) ranged from 0.14 L/day to 0.22 L/day and the mean half-life ranged from 22 to 31 days in plaque psoriasis subjects following intravenous and subcutaneous administration across all psoriasis trials. Intravenous use is not recommended [see Dosage and Administration (2)]. Dose LinearitySecukinumab exhibited dose-proportional pharmacokinetics in subjects with psoriasis over dose range from 25 mg (approximately 0.083 times the recommended dose) to 300 mg following subcutaneous administrations.WeightSecukinumab clearance and volume of distribution increase as body weight increases. Specific PopulationsPatients with Hepatic or Renal ImpairmentNo formal trial of the effect of hepatic or renal impairment on the pharmacokinetics of secukinumab was conducted.Geriatric PatientsPopulation pharmacokinetic analysis indicated that the clearance of secukinumab was not significantly influenced by age in adult subjects with plaque psoriasis, PsA and AS. Subjects who are 65 years or older had apparent clearance of secukinumab similar to subjects less than 65 years old.Pediatric PatientsIn pool of the two pediatric trials, subjects with moderate to severe plaque psoriasis (6 years of age and older) were administered secukinumab at the recommended pediatric dosing regimen. At Week 24, secukinumab steady state mean +- SD serum trough concentrations were 32.6 +- 10.8 mcg/mL (n 8), 19.8 +- 6.96 mcg/mL (n 24), and 27.3 +- 10.1 mcg/mL (n 36), in subjects weighing 25 kg and receiving 75 mg of secukinumab, subjects weighing >= 25 and 50 kg and receiving 75 mg of secukinumab, and subjects weighing >= 50 kg and receiving 150 mg of secukinumab, respectively.In pediatric study, JPsA and ERA patients (2 to less than 18 years of age) were administered secukinumab at the recommended pediatric dosing regimen. At Week 24, patients weighing >=15 kg and 50 kg, and patients weighing >= 50 kg had mean +- SD steady-state trough concentration of 25.2 +- 5.45 mcg/mL (n 10) and 27.9 +- 9.57 mcg/mL (n 19), respectively.Drug InteractionsCytochrome P450 SubstratesIn adult subjects with plaque psoriasis, midazolam (CYP3A4 substrate) pharmacokinetics was similar when administered alone, or when administered following either single or five weekly subcutaneous administrations of 300 mg secukinumab [see Drug Interactions (7.3)].

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.Adult Plaque PsoriasisA total of 3430 plaque psoriasis subjects were treated with COSENTYX in controlled and uncontrolled clinical trials. Of these, 1641 subjects were exposed for at least year.Four placebo-controlled Phase trials in plaque psoriasis subjects were pooled to evaluate the safety of COSENTYX in comparison to placebo up to 12 weeks after treatment initiation, in Trials PsO1, PsO2, PsO3, and PsO4. In total, 2077 subjects were evaluated (691 to COSENTYX 300 mg group, 692 to COSENTYX 150 mg group, and 694 to placebo group). Subjects randomized to COSENTYX received 300 mg or 150 mg doses subcutaneously at Weeks 0, 1, 2, 3, and followed by the same dose every weeks [see Clinical Studies (14)].Table summarizes the adverse reactions that occurred at rate of at least 1% and at higher rate in the COSENTYX groups than the placebo group during the 12-week placebo-controlled period of the placebo-controlled trials.Table 2: Adverse Reactions Reported by Greater Than 1% of Subjects With Plaque Psoriasis Through Week 12 in Trials PsO1, PsO2, PsO3, and PsO4COSENTYXAdverse Reactions300 mg(N 691)n (%)150 mg(N 692)n (%)Placebo(N 694)n (%)Nasopharyngitis79 (11.4)85 (12.3)60 (8.6)Diarrhea28 (4.1)18 (2.6)10 (1.4)Upper respiratory tract infection17 (2.5)22 (3.2)5 (0.7)Rhinitis10 (1.4)10 (1.4)5 (0.7)Oral herpes9 (1.3)1 (0.1)2 (0.3)Pharyngitis8 (1.2)7 (1.0)0 (0)Urticaria4 (0.6)8 (1.2)1 (0.1)Rhinorrhea8 (1.2)2 (0.3)1 (0.1)Adverse reactions that occurred at rates less than 1% in the placebo-controlled period of Trials PsO1, PsO2, PsO3, and PsO4 through Week 12 included: sinusitis, tinea pedis, conjunctivitis, tonsillitis, oral candidiasis, impetigo, otitis media, otitis externa, inflammatory bowel disease, increased liver transaminases, and neutropenia.InfectionsIn the placebo-controlled period of the clinical trials in plaque psoriasis (a total of 1382 subjects treated with COSENTYX and 694 subjects treated with placebo up to 12 weeks), infections were reported in 28.7% of subjects treated with COSENTYX compared with 18.9% of subjects treated with placebo. Serious infections occurred in 0.14% of subjects treated with COSENTYX and in 0.3% of subjects treated with placebo.Over the entire treatment period (a total of 3430 plaque psoriasis subjects treated with COSENTYX for up to 52 weeks for the majority of subjects), infections were reported in 47.5% of subjects treated with COSENTYX (0.9 per patient-year of follow-up). Serious infections were reported in 1.2% of subjects treated with COSENTYX (0.015 per patient-year of follow-up).Phase data showed an increasing trend for some types of infection with increasing serum concentration of secukinumab. Candida infections, herpes viral infections, staphylococcal skin infections, and infections requiring treatment increased as serum concentration of secukinumab increased.In the psoriasis open-label extension of Trials PsO1 and PsO2 (median follow-up of 3.9 years), representing 3582 subject-years of exposure, 74% of COSENTYX treated subjects reported infections (55 per 100 patient-years). Serious infections were reported in 4.5% of subjects (1.4 per 100 patient-years). Sepsis was reported in subjects (0.2 per 100 patient-years).Neutropenia was observed in controlled portion of clinical trials. Most cases of secukinumab-associated neutropenia were transient and reversible. No serious infections were associated with cases of neutropenia.In the open-label extension of Trials PsO1 and PsO2, neutropenia (ANC 1 x109/L) was reported in 1% of COSENTYX treated subjects (0.3 per 100 patient-years). Some cases of serious infections were associated with neutropenia; however the causal relationship was not established.Inflammatory Bowel DiseaseCases of inflammatory bowel disease, in some cases serious, were observed in clinical trials with COSENTYX. In the plaque psoriasis program, with 3430 subjects exposed to COSENTYX over the entire treatment period for up to 52 weeks (2725 patient-years), there were cases (0.11 per 100 patient-years) of exacerbation of Crohns disease, cases (0.08 per 100 patient-years) of exacerbation of ulcerative colitis, and cases (0.08 per 100 patient-years) of new onset ulcerative colitis. There were no cases in placebo subjects (N 793; 176 patient-years) during the 12-week placebo-controlled period.One case of exacerbation of Crohns disease was reported in open-labeled portions of clinical trials in plaque psoriasis.Hypersensitivity ReactionsAnaphylaxis and cases of urticaria occurred in COSENTYX treated subjects in clinical trials [see Warnings and Precautions (5.4)].Pediatric Plaque PsoriasisThe safety of COSENTYX was assessed in two Phase trials in pediatric subjects with plaque psoriasis.The first was randomized, double-blind, placebo and active-controlled, 236-week trial (Trial PsO6) that enrolled 162 pediatric subjects years of age and older, with severe plaque psoriasis (defined by PASI score >= 20, an IGA modified 2011 score of 4, and involving >= 10% of the body surface area) who were candidates for systemic therapy. The 162 subjects were randomized to receive placebo, biologic active control, or COSENTYX. In the COSENTYX groups, subjects with body weight 25 kg received 75 mg, subjects with body weight 25 to 50 kg received either 75 mg or 150 mg (2 times the recommended dose), and subjects with body weight >= 50 kg received either 150 mg or 300 mg (2 times the recommended dose).The second trial was randomized, open-label, 208-week trial (Trial PsO7; NCT03668613) of 84 subjects years of age and older with moderate to severe plaque psoriasis (defined by PASI score >= 12, IGA mod 2011 score of >= 3, and BSA involvement of >= 10% at randomization) who were randomized into two COSENTYX arms [Arm 1: 75 mg for body weight (BW) 50 kg or 150 mg for >= 50 kg and Arm 2: 75 mg for BW 25 kg, 150 mg for BW >= 25 kg and 50 kg, or 300 mg for BW >= 50 kg].The safety profile reported in these trials was consistent with the safety profile reported in adult plaque psoriasis trials.InfectionsOne case of methicillin-resistant Staphylococcus aureus (MRSA) toxic shock syndrome (TSS) was reported in COSENTYX treated subject during the placebo-controlled period. In the pediatric safety pool, which includes all subjects who took at least one dose of COSENTYX during the treatment periods [198 subjects (287 patient years)], 22 (11%) subjects reported >= CTCAE Grade neutropenia (>=1,000 to 1,500 cells/mm3) with 57% of subjects followed for one year or more and 30% of subjects followed for two years or more. During the placebo-controlled period which included total of 80 subjects treated with secukinumab and 41 subjects treated with placebo up to 12 weeks, >= CTCAE Grade neutropenia was reported in (4%) of the subjects treated with secukinumab compared with no subjects treated with placebo. No serious infections were associated with cases of neutropenia.Adult Psoriatic ArthritisCOSENTYX was studied in two placebo-controlled PsA trials with 1003 patients (703 patients on COSENTYX and 300 patients on placebo). Of the 703 patients who received COSENTYX, 299 patients received subcutaneous loading dose of COSENTYX (PsA1) and 404 patients received an intravenous loading dose of secukinumab (PsA2) followed by COSENTYX administered by subcutaneous injection every four weeks. During the 16-week placebo-controlled period of the trials in patients with PsA, the overall proportion of patients with adverse events was similar in the secukinumab and placebo-treatment groups (59% and 58%, respectively). The adverse events that occurred at proportion of at least 2% and at higher proportion in the COSENTYX groups than the placebo groups during the 16-week placebo-controlled period were nasopharyngitis, upper respiratory tract infection, headache, nausea, and hypercholesterolemia. The safety profile observed in patients with PsA treated with COSENTYX is consistent with the safety profile in psoriasis.Similar to the clinical trials in patients with psoriasis, there was an increased proportion of patients with infections in the COSENTYX groups (29%) compared to placebo group (26%).There were cases of Crohns disease and ulcerative colitis that include patients who experienced either exacerbations or the development of new disease. There were three cases of inflammatory bowel disease, of which two patients received secukinumab and one received placebo.Ankylosing SpondylitisCOSENTYX was studied in two placebo-controlled AS trials with 590 patients (394 patients on COSENTYX and 196 patients on placebo). Of the 394 patients who received COSENTYX, 145 patients received subcutaneous load of COSENTYX (study AS1), and 249 received an intravenous loading dose of secukinumab (study AS2) followed by COSENTYX administered by subcutaneous injection every four weeks. During the 16-week placebo-controlled period of the trials in patients with AS, the overall proportion of patients with adverse events was higher in the secukinumab groups than the placebo-treatment groups (66% and 59%, respectively). The adverse events that occurred at proportion of at least 2% and at higher proportion in the COSENTYX groups than the placebo groups during the 16-week placebo-controlled period were nasopharyngitis, nausea, and upper respiratory tract infection. The safety profile observed in patients with ankylosing spondylitis treated with COSENTYX is consistent with the safety profile in psoriasis. In third controlled study of AS (study AS3), the safety profile of the 300 mg dose of COSENTYX was consistent with the safety profile of the 150 mg dose of COSENTYX.Similar to clinical trials in patients with psoriasis, there was an increased proportion of patients with infections in the COSENTYX groups (31%) compared to the placebo group (18%).In the original AS program, with 571 patients exposed to COSENTYX there were cases of inflammatory bowel disease during the entire treatment period [5 Crohns (0.7 per 100 patient-years) and ulcerative colitis (0.4 per 100 patient-years)]. During the placebo-controlled 16-week period, there were Crohns disease exacerbations and new onset ulcerative colitis case that was serious adverse event in patients treated with COSENTYX compared to none of the patients treated with placebo. During the remainder of the study when all patients received COSENTYX, patient developed Crohns disease, patients had Crohns exacerbations, patient developed ulcerative colitis, and patient had an ulcerative colitis exacerbation.Non-Radiographic Axial SpondyloarthritisCOSENTYX was studied in one randomized, double-blind, placebo-controlled nr-axSpA trial with 555 patients (185 patients on with load COSENTYX, 184 patients on without load COSENTYX and 186 patients on placebo). The safety profile for patients with nr-axSpA treated with COSENTYX was overall similar to the safety profile seen in patients with AS and other previous experience with COSENTYX. Patients in nr-axSpA1 study who received the loading dosing regimen compared to those without the loading regimen, had higher incidence of infections and infestations (92 per 100 patient-years vs 72 per 100 patient years), including nasopharyngitis, upper respiratory tract infection and urinary tract infection, and gastrointestinal disorders (27 per 100 patient-years vs 22 per 100 patient-years), including gastritis, lower abdominal pain, colitis, diarrhea, and hematochezia.Juvenile Psoriatic Arthritis and Enthesitis-Related ArthritisCOSENTYX was studied in one double-blind, placebo-controlled, event-driven, randomized trial in 86 pediatric patients aged to 18 years old with Juvenile Psoriatic Arthritis (JPsA) and ERA. The safety profile reported in this study was consistent with the safety profile of secukinumab.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. COSENTYX is contraindicated in patients with previous serious hypersensitivity reaction to secukinumab or to any of the excipients in COSENTYX. Cases of anaphylaxis have been reported during treatment with COSENTYX [see Warnings and Precautions (5.4)]. Serious hypersensitivity to secukinumab or any excipients in COSENTYX. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Secukinumab, recombinant human monoclonal IgG1/ antibody, is an interleukin-17A antagonist. It is expressed in recombinant Chinese Hamster Ovary (CHO) cell line. Secukinumab has molecular mass of approximately 151 kDa; both heavy chains of secukinumab contain oligosaccharide chains.COSENTYX InjectionCOSENTYX injection is sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for subcutaneous use. COSENTYX is supplied in single-dose Sensoready pen with 27-gauge fixed 1/2 -inch needle, or single-dose prefilled syringe with 27-gauge fixed 1/2 -inch needle. The removable cap of the COSENTYX Sensoready pen or prefilled syringe contains natural rubber latex.Each COSENTYX Sensoready pen or prefilled syringe contains 150 mg of secukinumab formulated in: L-histidine/histidine hydrochloride monohydrate (3.103 mg), L-methionine (0.746 mg), polysorbate 80 (0.2 mg), trehalose dihydrate (75.67 mg), and Sterile Water for Injection, USP, at pH of 5.8.Each COSENTYX 75 mg/0.5 mL prefilled syringe contains 75 mg of secukinumab formulated in: L-histidine/histidine hydrochloride monohydrate (1.552 mg), L-methionine (0.373 mg), polysorbate 80 (0.1 mg), trehalose dihydrate (37.83 mg), and Sterile Water for Injection, USP, at pH of 5.8. COSENTYX for InjectionCOSENTYX for injection is supplied as sterile, preservative free, white to slightly yellow, lyophilized powder in single-dose vials for subcutaneous use after reconstitution. Each COSENTYX vial contains 150 mg of secukinumab formulated in L-histidine/histidine hydrochloride monohydrate (4.656 mg), polysorbate 80 (0.6 mg), and sucrose (92.43 mg). Following reconstitution with mL Sterile Water for Injection, USP, the resulting pH is approximately 5.8.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Prior to COSENTYX initiation, complete all age appropriate vaccinations, evaluate patients for tuberculosis (TB) (2.1). See Full Prescribing Information for instructions on preparation and administration of COSENTYX. (2.7, 2.8)Plaque Psoriasis:Adults: Recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and followed by 300 mg every weeks. For some patients, dose of 150 mg may be acceptable. (2.2)Pediatric Patients Years and Older: Recommended dosage based on body weight and administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every weeks thereafter (2.2):Body Weight at Time of DosingRecommended DoseLess than 50 kg75 mgGreater than or equal to 50 kg150 mgPsoriatic Arthritis:Adults: Recommended dosages are:For PsA patients with coexistent moderate to severe plaque psoriasis, use the dosage and administration for plaque psoriasis. (2.2)For other PsA patients, administer with or without loading dosage.With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafterWithout loading dosage: 150 mg every weeksIf patient continues to have active PsA, consider dosage of 300 mg every weeks. (2.3) Pediatric Patients years and older: Recommended dosage is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every weeks thereafter.For patients weighing >= 15 kg and 50 kg the dose is 75 mg.For patients weighing >= 50 kg the dose is 150 mg. (2.3)Ankylosing Spondylitis: Administer with or without loading dosage.The recommended dosages are:With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter.Without loading dosage: 150 mg every weeks.If patient continues to have active ankylosing spondylitis, consider dosage of 300 mg every weeks. (2.4) Non-Radiographic Axial Spondyloarthritis: Administer with or without loading dosage. The recommended dosage is:With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter. (2.5)Without loading dosage: 150 mg every weeks. (2.5) Enthesitis-Related Arthritis: Recommended dosage is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every weeks thereafter.For patients weighing >= 15 kg and 50 kg the dose is 75 mg.For patients weighing >= 50 kg the dose is 150 mg. (2.6) Prior to COSENTYX initiation, complete all age appropriate vaccinations, evaluate patients for tuberculosis (TB) (2.1). See Full Prescribing Information for instructions on preparation and administration of COSENTYX. (2.7, 2.8). Plaque Psoriasis:Adults: Recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and followed by 300 mg every weeks. For some patients, dose of 150 mg may be acceptable. (2.2)Pediatric Patients Years and Older: Recommended dosage based on body weight and administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every weeks thereafter (2.2):. Adults: Recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and followed by 300 mg every weeks. For some patients, dose of 150 mg may be acceptable. (2.2). Pediatric Patients Years and Older: Recommended dosage based on body weight and administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every weeks thereafter (2.2):. Psoriatic Arthritis:Adults: Recommended dosages are:For PsA patients with coexistent moderate to severe plaque psoriasis, use the dosage and administration for plaque psoriasis. (2.2)For other PsA patients, administer with or without loading dosage.With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafterWithout loading dosage: 150 mg every weeksIf patient continues to have active PsA, consider dosage of 300 mg every weeks. (2.3) For PsA patients with coexistent moderate to severe plaque psoriasis, use the dosage and administration for plaque psoriasis. (2.2). For other PsA patients, administer with or without loading dosage.With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafterWithout loading dosage: 150 mg every weeksIf patient continues to have active PsA, consider dosage of 300 mg every weeks. (2.3) With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter. Without loading dosage: 150 mg every weeks. If patient continues to have active PsA, consider dosage of 300 mg every weeks. (2.3). For patients weighing >= 15 kg and 50 kg the dose is 75 mg.. For patients weighing >= 50 kg the dose is 150 mg. (2.3). Ankylosing Spondylitis: Administer with or without loading dosage.The recommended dosages are:With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter.Without loading dosage: 150 mg every weeks.If patient continues to have active ankylosing spondylitis, consider dosage of 300 mg every weeks. (2.4) With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter.. Without loading dosage: 150 mg every weeks.. If patient continues to have active ankylosing spondylitis, consider dosage of 300 mg every weeks. (2.4). Non-Radiographic Axial Spondyloarthritis: Administer with or without loading dosage. The recommended dosage is:With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter. (2.5)Without loading dosage: 150 mg every weeks. (2.5) With loading dosage: 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter. (2.5). Without loading dosage: 150 mg every weeks. (2.5). Enthesitis-Related Arthritis: Recommended dosage is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every weeks thereafter.For patients weighing >= 15 kg and 50 kg the dose is 75 mg.For patients weighing >= 50 kg the dose is 150 mg. (2.6) For patients weighing >= 15 kg and 50 kg the dose is 75 mg.. For patients weighing >= 50 kg the dose is 150 mg. (2.6). 2.1 Testing and Procedures Prior to Treatment Initiation. Perform the following evaluations prior to COSENTYX initiation:Evaluate patients for tuberculosis (TB) infection. COSENTYX initiation is not recommended in patients with active TB infection. Initiate treatment of latent TB prior to initiation of COSENTYX [see Warnings and Precautions (5.2)].Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with COSENTYX [see Warnings and Precautions (5.6)].. Perform the following evaluations prior to COSENTYX initiation:Evaluate patients for tuberculosis (TB) infection. COSENTYX initiation is not recommended in patients with active TB infection. Initiate treatment of latent TB prior to initiation of COSENTYX [see Warnings and Precautions (5.2)].Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with COSENTYX [see Warnings and Precautions (5.6)].. Evaluate patients for tuberculosis (TB) infection. COSENTYX initiation is not recommended in patients with active TB infection. Initiate treatment of latent TB prior to initiation of COSENTYX [see Warnings and Precautions (5.2)].. Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with COSENTYX [see Warnings and Precautions (5.6)].. 2.2 Plaque Psoriasis. AdultsThe recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and followed by 300 mg every weeks. Each 300 mg dosage is given as subcutaneous injections of 150 mg.For some patients, dose of 150 mg may be acceptable.Pediatric PatientsThe recommended dosage for pediatric patients years of age and older is based on body weight (Table 1) and administered by subcutaneous injection at Weeks 0, 1, 2, 3, and followed by dosing every weeks.Table 1: Recommended Dose of COSENTYX for Pediatric Patients Years of Age and Older with Plaque PsoriasisBody Weight at Time of DosingRecommended DoseLess than 50 kg75 mgGreater than or equal to 50 kg150 mg. 2.3 Psoriatic Arthritis. AdultsFor PsA patients with coexistent moderate to severe plaque psoriasis, use the dosing and administration recommendations for plaque psoriasis [see Dosage and Administration (2.1)].For other PsA patients, administer COSENTYX with or without loading dosage by subcutaneous injection. The recommended dosage:With loading dosage is 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafterWithout loading dosage is 150 mg every weeksIf patient continues to have active PsA, consider dosage of 300 mg every weeks.Pediatric PatientsThe recommended dose based on body weight is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every weeks thereafter.For patients weighing >= 15 kg and 50 kg the recommended dose is 75 mgFor patients weighing >= 50 kg the recommended dose is 150 mgCOSENTYX may be administered with or without methotrexate.. With loading dosage is 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter. Without loading dosage is 150 mg every weeks. If patient continues to have active PsA, consider dosage of 300 mg every weeks.. For patients weighing >= 15 kg and 50 kg the recommended dose is 75 mg. For patients weighing >= 50 kg the recommended dose is 150 mg. 2.4 Ankylosing Spondylitis. Administer COSENTYX with or without loading dosage by subcutaneous injection. The recommended dosage:With loading dosage is 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafterWithout loading dosage is 150 mg every weeksIf patient continues to have active AS, consider dosage of 300 mg every weeks.. With loading dosage is 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter. Without loading dosage is 150 mg every weeks. If patient continues to have active AS, consider dosage of 300 mg every weeks.. 2.5 Non-Radiographic Axial Spondyloarthritis. Administer COSENTYX with or without loading dosage by subcutaneous injection. The recommended dosage:With loading dosage is 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafterWithout loading dosage is 150 mg every weeks. With loading dosage is 150 mg at Weeks 0, 1, 2, 3, and and every weeks thereafter. Without loading dosage is 150 mg every weeks. 2.6 Enthesitis-Related Arthritis. The recommended dose based on body weight is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every weeks thereafter.For patients weighing >= 15 kg and 50 kg the recommended dose is 75 mgFor patients weighing >= 50 kg the recommended dose is 150 mg. For patients weighing >= 15 kg and 50 kg the recommended dose is 75 mg. For patients weighing >= 50 kg the recommended dose is 150 mg. 2.7 Important Administration Instructions. There are four presentations for COSENTYX (i.e., Sensoready pen, prefilled syringes [150 mg/mL, 75 mg/0.5 mL], and lyophilized powder in vial for reconstitution). The COSENTYX Instructions for Use for each presentation contains more detailed instructions on the preparation and administration of COSENTYX [see Instructions for Use]. The lyophilized powder in vial for reconstitution is for healthcare provider use only.COSENTYX is intended for use under the guidance and supervision of physician. Sensoready PenAdult patients may self-administer COSENTYX or be injected by caregiver after proper training in subcutaneous injection technique using the Sensoready pen.Pediatric patients should not self-administer COSENTYX using the Sensoready pen. An adult caregiver should prepare and inject COSENTYX after proper training in subcutaneous injection technique using the Sensoready pen.Prefilled SyringeAdult patients may self-administer COSENTYX or be injected by caregiver after proper training in subcutaneous injection technique using the prefilled syringe.Pediatric patients should not self-administer COSENTYX using the prefilled syringe. An adult caregiver should prepare and inject COSENTYX after proper training in subcutaneous injection technique using the prefilled syringe.Administration InstructionsAdminister each injection at different anatomic location (such as upper arms, thighs, or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis. Administration of COSENTYX in the upper, outer arm may be performed by caregiver or healthcare provider.. 2.8 Preparation for Use of COSENTYX Sensoready(R) Pen and Prefilled Syringe. Before injection, remove COSENTYX Sensoready pen or COSENTYX prefilled syringe from the refrigerator and allow COSENTYX to reach room temperature (15 to 30 minutes) without removing the needle cap.The removable cap of the COSENTYX Sensoready pen and the COSENTYX prefilled syringe contain natural rubber latex and should not be handled by latex-sensitive individuals [see Warnings and Precautions (5.5)].Inspect COSENTYX visually for particulate matter and discoloration prior to administration. COSENTYX injection is clear to slightly opalescent, colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy. COSENTYX does not contain preservatives; therefore, administer the Sensoready pen or prefilled syringe within hour after removal from the refrigerator. Discard any unused product remaining in the Sensoready pen or prefilled syringe.. 2.9 Reconstitution and Preparation of COSENTYX Lyophilized Powder. COSENTYX lyophilized powder should be prepared and reconstituted with Sterile Water for Injection by trained healthcare provider using aseptic technique and without interruption. The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes.a) Remove the vial of COSENTYX lyophilized powder from the refrigerator and allow to stand for 15 to 30 minutes to reach room temperature. Ensure the Sterile Water for Injection is at room temperature.b) Slowly inject mL of Sterile Water for Injection into the vial containing COSENTYX lyophilized powder and direct the stream of Sterile Water for Injection onto the lyophilized powder.c) Tilt the vial at an angle of approximately 45 degrees and gently rotate between the fingertips for approximately minute. Do not shake or invert the vial.d) Allow the vial to stand for about 10 minutes at room temperature to allow for dissolution. Note that foaming may occur.e) Tilt the vial at an angle of approximately 45 degrees and gently rotate between the fingertips for approximately minute. Do not shake or invert the vial.f) Allow the vial to stand undisturbed at room temperature for approximately minutes. The reconstituted COSENTYX solution should be essentially free of visible particles, clear to opalescent, and colorless to slightly yellow. Do not use if the lyophilized powder has not fully dissolved or if the liquid contains visible particles, is cloudy or discolored. g) Prepare the required number of vials (1 vial for the 150 mg dose or vials for the 300 mg dose).h) The COSENTYX reconstituted solution contains 150 mg of secukinumab in mL of solution. After reconstitution, use the solution immediately or store in the refrigerator at 2oC to 8oC (36oF to 46oF) for up to 24 hours. Do not freeze.i) If stored at 2oC to 8oC (36oF to 46oF), allow the reconstituted COSENTYX solution to reach room temperature (15 to 30 minutes) before administration. COSENTYX does not contain preservatives; therefore, administer within hour after removal from 2oC to 8oC (36oF to 46oF) storage.

INSTRUCTIONS FOR USE SECTION.

INSTRUCTIONS FOR USECOSENTYX(R) (koe-sen-tix)(secukinumab)For InjectionThe following information is intended for medical or healthcare professionals only.IMPORTANT:The single-dose vial contains 150 mg of COSENTYX for reconstitution with Sterile Water for Injection (SWFI). Do not use the vial after the expiry date shown on the outer box or vial. If it has expired, return the entire pack to the pharmacy.The preparation of the solution for subcutaneous injection shall be done without interruption ensuring that aseptic technique is used. The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes.Throw away (dispose of) the used syringe right away after use. Do not re-use syringe. See How should dispose of used syringe at the end of this Instructions for Use.How should store COSENTYXStore the vial of COSENTYX in the refrigerator between 2C to 8C (36F to 46F).To prepare COSENTYX 150 mg for injection, please adhere to the following instructions:Instructions for reconstitution of COSENTYX 150 mg for injection:Step 1. Remove the vial of COSENTYX 150 mg for injection from the refrigerator and allow to stand for 15 to 30 minutes to reach room temperature. Ensure the Sterile Water for Injection (SWFI) is at room temperature. Step 2.Reconstitute the lyophilized powder by slowly injecting mL of Sterile Water for Injection (SWFI) into the vial. Direct the stream of SWFI onto the lyophilized powder (See Figure A). Figure AStep 3. Tilt the vial to an angle of approximately 45 degrees and gently rotate between the fingertips for approximately minute. Do not shake or invert the vial (See Figure B). Step 4. Keep the vial standing at room temperature for minimum of 10 minutes to allow for dissolution. Note that foaming of the solution may occur. Step 5. Tilt the vial to an angle of approximately 45 degrees and gently rotate between the fingertips for approximately minute. Do not shake or invert the vial (See Figure B). Step 6. Allow the vial to stand undisturbed at room temperature for approximately minutes. The resulting solution should be clear. Its color may vary from colorless to slightly yellow. Do not use if the lyophilized powder has not fully dissolved or if the liquid contains visible particles, is cloudy or is discolored. Step 7. Prepare the required number of vials (1 vial for the 150 mg dose or vials for the 300 mg dose).Figure BAfter preparation, use the solution for subcutaneous injection immediately or store at 2C to 8C (36F to 46F) for up to 24 hours. Do not freeze. After storage at 2C to 8C (36F to 46F), allow the reconstituted solution to come to room temperature (15 to 30 minutes) before administration. Administer the solution within hour after removal from the 2C to 8C (36F to 46F) storage.Instructions for administration of COSENTYX solution:Step 1. Tilt the vial to an angle of approximately 45 degrees and position the needle tip at the very bottom of the solution in the vial when drawing the solution into the syringe. DO NOT invert the vial. Step 2. Carefully withdraw slightly more than mL of the solution for subcutaneous injection from the vial into 1 mL graduated disposable syringe using suitable needle (e.g., 21G 2) (See Figure C). This needle will only be used for withdrawing COSENTYX into the disposable syringe. Prepare the required number of syringes (1 syringe for the 150 mg dose or syringes for the 300 mg dose).Figure CStep 3. With the needle pointing upward, gently tap the syringe to move any air bubbles to the top (See Figure D).Figure DStep 4. Replace the attached needle with 27G 1/2 needle (See Figure E). Step 5. Expel the air bubbles and advance the plunger to the mL mark. Step 6. Clean the injection site with an alcohol wipe.Figure EStep 7. Inject the COSENTYX solution subcutaneously into the front of thighs, lower abdomen [but not the area inches around the navel (belly button)] or outer upper arms (See Figure F). Choose different site each time an injection is administered. Do not inject into areas where the skin is tender, bruised, red, scaly or hard, or in an area of skin that is affected by psoriasis. Avoid areas with scars or stretch marks.Figure FHow should dispose of used syringeAny remaining solution in the vial must not be used and must be discarded in accordance with local requirements. Vials are for single use only.Put the used syringes and needles in FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the syringes and needles in your household trash.If you do not have an FDA-cleared sharps disposal container, you may use household container that is:made of heavy-duty plastic,can be closed with tight-fitting, puncture-resistant lid, without sharps being able to come out,upright and stable during use,leak-resistant, andproperly labeled to warn of hazardous waste inside the container.When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDAs website at: http://www.fda.gov/safesharpsdisposal.This Instructions for Use has been approved by the U.S. Food and Drug Administration.Manufactured by: Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936 US License Number 1244Issued: December 2021(C) NovartisT2021-164. The single-dose vial contains 150 mg of COSENTYX for reconstitution with Sterile Water for Injection (SWFI). Do not use the vial after the expiry date shown on the outer box or vial. If it has expired, return the entire pack to the pharmacy.. The preparation of the solution for subcutaneous injection shall be done without interruption ensuring that aseptic technique is used. The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes.. Throw away (dispose of) the used syringe right away after use. Do not re-use syringe. See How should dispose of used syringe at the end of this Instructions for Use.. Store the vial of COSENTYX in the refrigerator between 2C to 8C (36F to 46F).. made of heavy-duty plastic,. can be closed with tight-fitting, puncture-resistant lid, without sharps being able to come out,. upright and stable during use,. leak-resistant, and. properly labeled to warn of hazardous waste inside the container.. Figure A. Figure B. Figure C. Figure D. Figure E. Figure F.

LACTATION SECTION.

8.2 Lactation. Risk SummaryIt is not known whether secukinumab is excreted in human milk or absorbed systemically after ingestion. There are no data on the effects of COSENTYX on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for COSENTYX and any potential adverse effects on the breastfed child from COSENTYX or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Secukinumab is human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Injection: 150 mg/mL as clear to opalescent, colorless to slightly yellowish solution in single-dose Sensoready penInjection: 150 mg/mL as clear to opalescent, colorless to slightly yellowish solution in single-dose prefilled syringeInjection: 75 mg/0.5 mL as clear to opalescent, colorless to slightly yellowish solution in single-dose prefilled syringe (for pediatric patients less than 50 kg)For injection: 150 mg white lyophilized powder in single-dose vial for reconstitution (for healthcare professional use only). Injection: 150 mg/mL as clear to opalescent, colorless to slightly yellowish solution in single-dose Sensoready pen. Injection: 150 mg/mL as clear to opalescent, colorless to slightly yellowish solution in single-dose prefilled syringe. Injection: 75 mg/0.5 mL as clear to opalescent, colorless to slightly yellowish solution in single-dose prefilled syringe (for pediatric patients less than 50 kg). For injection: 150 mg white lyophilized powder in single-dose vial for reconstitution (for healthcare professional use only). Injection: 150 mg/mL solution in single-dose Sensoready(R) pen and in single-dose prefilled syringe. (3)Injection: 75 mg/0.5 mL solution in single-dose prefilled syringe (for pediatric patients). (3)For Injection: 150 mg, lyophilized powder in single-dose vial for reconstitution (for healthcare professional use only). (3). Injection: 150 mg/mL solution in single-dose Sensoready(R) pen and in single-dose prefilled syringe. (3). Injection: 75 mg/0.5 mL solution in single-dose prefilled syringe (for pediatric patients). (3). For Injection: 150 mg, lyophilized powder in single-dose vial for reconstitution (for healthcare professional use only). (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. CYP450 SubstratesThe formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNF, IFN) during chronic inflammation.Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those with narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment of the CYP450 substrate as needed [see Clinical Pharmacology (12.3)].

GERIATRIC USE SECTION.

8.5 Geriatric Use. Of the 3430 plaque psoriasis subjects exposed to COSENTYX in clinical trials, total of 230 were 65 years or older, and 32 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 years and older was not sufficient to determine whether they responded differently from younger subjects.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 How Supplied. COSENTYX (secukinumab) injection is clear to opalescent, colorless to slightly yellowish solution available as follows:COSENTYX Sensoready pen:NDC 0078-0639-41: Carton of two 150 mg/mL (300 mg dose) single-dose Sensoready pens (injection)NDC 0078-0639-68: Carton of one 150 mg/mL single-dose Sensoready pen (injection)COSENTYX prefilled syringe:NDC 0078-0639-98: Carton of two 150 mg/mL (300 mg dose) single-dose prefilled syringes (injection)NDC 0078-0639-97: Carton of one 150 mg/mL single-dose prefilled syringe (injection)COSENTYX prefilled syringe (for pediatric patients less than 50 kg):NDC 0078-1056-97: Carton of one 75 mg/0.5 mL single-dose prefilled syringe (injection)The removable cap of the COSENTYX 150 mg/mL Sensoready pen and prefilled syringe, and 75 mg/0.5 mL prefilled syringe contains natural rubber latex. Each Sensoready pen and prefilled syringe is equipped with needle safety guard.COSENTYX (secukinumab) for injection is white lyophilized powder for healthcare professional use only available as follows:NDC 0078-0657-61: Carton of one 150 mg lyophilized powder in single-dose vial (for injection). NDC 0078-0639-41: Carton of two 150 mg/mL (300 mg dose) single-dose Sensoready pens (injection). NDC 0078-0639-68: Carton of one 150 mg/mL single-dose Sensoready pen (injection). NDC 0078-0639-98: Carton of two 150 mg/mL (300 mg dose) single-dose prefilled syringes (injection). NDC 0078-0639-97: Carton of one 150 mg/mL single-dose prefilled syringe (injection). NDC 0078-1056-97: Carton of one 75 mg/0.5 mL single-dose prefilled syringe (injection). NDC 0078-0657-61: Carton of one 150 mg lyophilized powder in single-dose vial (for injection). 16.2 Storage and Handling. Refrigerate COSENTYX Sensoready pens, prefilled syringes, and vials at 2oC to 8oC (36oF to 46oF). Keep the product in the original carton to protect from light until the time of use. Do not freeze. To avoid foaming do not shake. COSENTYX does not contain preservative; discard any unused portion.If necessary, COSENTYX Sensoready pens and 150 mg/mL prefilled syringes may be stored for up to days at room temperature not to exceed 30C (86F). Write the date COSENTYX was removed from the refrigerator in the space provided on the carton. If unused and not stored above 30C (86F), COSENTYX Sensoready pens and 150 mg/mL prefilled syringes may be returned to the refrigerator. Throw away COSENTYX if it has been kept outside of the refrigerator and not been used in over days.

IMMUNOGENICITY.

6.2 Immunogenicity. As with all therapeutic proteins, there is the potential for immunogenicity. The immunogenicity of COSENTYX was evaluated using an electrochemiluminescence-based bridging immunoassay. Less than 1% of subjects treated with COSENTYX developed antibodies to secukinumab in up to 52 weeks of treatment. However, this assay has limitations in detecting anti-secukinumab antibodies in the presence of secukinumab; therefore, the incidence of antibody development might not have been reliably determined. Of the subjects who developed antidrug antibodies, approximately one-half had antibodies that were classified as neutralizing. Neutralizing antibodies were not associated with loss of efficacy. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to COSENTYX with the incidences of antibodies to other products may be misleading.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. COSENTYX is human interleukin-17A antagonist indicated for the treatment of:moderate to severe plaque psoriasis in patients years and older who are candidates for systemic therapy or phototherapy (1.1)active psoriatic arthritis (PsA) in patients years of age and older (1.2)adults with active ankylosing spondylitis (AS) (1.3)adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation (1.4)active enthesitis-related arthritis (ERA) in patients years of age and older (1.5). moderate to severe plaque psoriasis in patients years and older who are candidates for systemic therapy or phototherapy (1.1). active psoriatic arthritis (PsA) in patients years of age and older (1.2). adults with active ankylosing spondylitis (AS) (1.3). adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation (1.4). active enthesitis-related arthritis (ERA) in patients years of age and older (1.5). 1.1 Plaque Psoriasis. COSENTYX(R) is indicated for the treatment of moderate to severe plaque psoriasis in patients years and older who are candidates for systemic therapy or phototherapy.. 1.2 Psoriatic Arthritis. COSENTYX is indicated for the treatment of active psoriatic arthritis (PsA) in patients years of age and older.. 1.3 Ankylosing Spondylitis. COSENTYX is indicated for the treatment of adult patients with active ankylosing spondylitis (AS).. 1.4 Non-Radiographic Axial Spondyloarthritis. COSENTYX is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.. 1.5 Enthesitis-Related Arthritis. COSENTYX is indicated for the treatment of active enthesitis-related arthritis (ERA) in patients years of age and older.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of COSENTYX. Some published literature suggests that IL-17A directly promotes cancer cell invasion in vitro, whereas other reports indicate IL-17A promotes T-cell mediated tumor rejection. Depletion of IL-17A with neutralizing antibody inhibited tumor development in mice. The relevance of experimental findings in mouse models for malignancy risk in humans is unknown.No effects on fertility were observed in male and female mice that were administered murine analog of secukinumab at subcutaneous doses up to 150 mg/kg once weekly prior to and during the mating period.

OVERDOSAGE SECTION.

10 OVERDOSAGE. Doses up to 30 mg/kg intravenously have been administered in clinical trials without dose-limiting toxicity. In the event of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. NDC 0078-0639-97Cosentyx(R) (secukinumab)InjectionSingle-dose Prefilled Syringe150 mg/mL1 Prefilled SyringeATTENTION: Dispense with enclosed Medication Guide.For Subcutaneous Use OnlySterile Solution Contains No PreservativeCaution: Contains Natural Rubber Latex Which May Cause Allergic Reaction.Rx onlyNOVARTIS. PRINCIPAL DISPLAY PANELNDC 0078-0639-97Cosentyx(R)(secukinumab)InjectionSingle-dose Prefilled Syringe150 mg/mL1 Prefilled SyringeATTENTION: Dispense with enclosed Medication Guide.For Subcutaneous Use OnlySterile Solution Contains No PreservativeCaution: Contains Natural Rubber Latex Which May Cause Allergic Reaction.Rx onlyNOVARTIS.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of COSENTYX have been established in pediatric subjects aged years and older with moderate to severe plaque psoriasis [see Adverse Reactions (6.1), Clinical Studies (14.2)]. Safety and effectiveness of COSENTYX in pediatric patients with plaque psoriasis below the age of years have not been established.The safety and effectiveness of COSENTYX have been established in patients weighing 15 kg or more with JPsA (2 years and older) and ERA (4 years and older) [see Adverse Reactions (6.1), Clinical Studies (14.6)].The safety and effectiveness of COSENTYX in pediatric patients below the age of years and with body weight less than 15 kg have not been established.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Elevated levels of IL-17A are found in psoriatic plaques. Treatment with COSENTYX may reduce epidermal neutrophils and IL-17A levels in psoriatic plaques. Serum levels of total IL-17A (free and secukinumab-bound IL-17A) measured at Week and Week 12 were increased following secukinumab treatment. These pharmacodynamic activities are based on small exploratory studies. The relationship between these pharmacodynamic activities and the mechanism(s) by which secukinumab exerts its clinical effects is unknown.Increased numbers of IL-17A producing lymphocytes and innate immune cells and increased levels of IL-17A have been found in the blood of patients with PsA and AS. Increased numbers of IL-17A producing lymphocytes have also been found in patients with nr-axSpA.Immune Response to Non-Live Vaccines During TreatmentHealthy individuals who received single 150 mg dose of COSENTYX weeks prior to vaccination with non-U.S. approved group meningococcal polysaccharide conjugate vaccine and non-U.S. approved inactivated seasonal influenza vaccine had similar antibody responses compared to individuals who did not receive COSENTYX prior to vaccination. The clinical effectiveness of meningococcal and influenza vaccines has not been assessed in patients undergoing treatment with COSENTYX [see Warnings and Precautions (5.6)].

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. The pharmacokinetic (PK) properties of secukinumab observed in PsA, AS and nr-axSpA patients were similar to the PK properties displayed in plaque psoriasis patients.AbsorptionFollowing single subcutaneous dose of either 150 mg (one-half the recommended dose) or 300 mg in plaque psoriasis subjects, secukinumab reached peak mean (+- SD) serum concentrations (Cmax) of 13.7 +- 4.8 mcg/mL and 27.3 +- 9.5 mcg/mL, respectively, by approximately days post dose.Following multiple subcutaneous doses of secukinumab, the mean (+- SD) serum trough concentrations of secukinumab ranged from 22.8 +- 10.2 mcg/mL (150 mg) to 45.4 +- 21.2 mcg/mL (300 mg) at Week 12. At the 300 mg dose at Week and Week 12, the mean trough concentrations resulted from the Sensoready pen were 23% to 30% higher than those from the lyophilized powder and 23% to 26% higher than those from the prefilled syringe based on cross-study comparisons.Steady-state concentrations of secukinumab were achieved by Week 24 following the every 4-week dosing regimens. The mean (+- SD) steady-state trough concentrations ranged from 16.7 +- 8.2 mcg/mL (150 mg) to 34.4 +- 16.6 mcg/mL (300 mg).In healthy subjects and subjects with plaque psoriasis, secukinumab bioavailability ranged from 55% to 77% following subcutaneous dose of 150 mg (one-half the recommended dose) or 300 mg.DistributionThe mean volume of distribution during the terminal phase (Vz) following single intravenous administration ranged from 7.10 to 8.60 in plaque psoriasis subjects. Intravenous use is not recommended [see Dosage and Administration (2)].Secukinumab concentrations in interstitial fluid in lesional and non-lesional skin of plaque psoriasis subjects ranged from 27% to 40% of those in serum at and weeks after single subcutaneous dose of secukinumab 300 mg.EliminationMetabolismThe metabolic pathway of secukinumab has not been characterized. As human IgG1 monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.ExcretionThe mean systemic clearance (CL) ranged from 0.14 L/day to 0.22 L/day and the mean half-life ranged from 22 to 31 days in plaque psoriasis subjects following intravenous and subcutaneous administration across all psoriasis trials. Intravenous use is not recommended [see Dosage and Administration (2)]. Dose LinearitySecukinumab exhibited dose-proportional pharmacokinetics in subjects with psoriasis over dose range from 25 mg (approximately 0.083 times the recommended dose) to 300 mg following subcutaneous administrations.WeightSecukinumab clearance and volume of distribution increase as body weight increases. Specific PopulationsPatients with Hepatic or Renal ImpairmentNo formal trial of the effect of hepatic or renal impairment on the pharmacokinetics of secukinumab was conducted.Geriatric PatientsPopulation pharmacokinetic analysis indicated that the clearance of secukinumab was not significantly influenced by age in adult subjects with plaque psoriasis, PsA and AS. Subjects who are 65 years or older had apparent clearance of secukinumab similar to subjects less than 65 years old.Pediatric PatientsIn pool of the two pediatric trials, subjects with moderate to severe plaque psoriasis (6 years of age and older) were administered secukinumab at the recommended pediatric dosing regimen. At Week 24, secukinumab steady state mean +- SD serum trough concentrations were 32.6 +- 10.8 mcg/mL (n 8), 19.8 +- 6.96 mcg/mL (n 24), and 27.3 +- 10.1 mcg/mL (n 36), in subjects weighing 25 kg and receiving 75 mg of secukinumab, subjects weighing >= 25 and 50 kg and receiving 75 mg of secukinumab, and subjects weighing >= 50 kg and receiving 150 mg of secukinumab, respectively.In pediatric study, JPsA and ERA patients (2 to less than 18 years of age) were administered secukinumab at the recommended pediatric dosing regimen. At Week 24, patients weighing >=15 kg and 50 kg, and patients weighing >= 50 kg had mean +- SD steady-state trough concentration of 25.2 +- 5.45 mcg/mL (n 10) and 27.9 +- 9.57 mcg/mL (n 19), respectively.Drug InteractionsCytochrome P450 SubstratesIn adult subjects with plaque psoriasis, midazolam (CYP3A4 substrate) pharmacokinetics was similar when administered alone, or when administered following either single or five weekly subcutaneous administrations of 300 mg secukinumab [see Drug Interactions (7.3)].

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryLimited available human data with COSENTYX use in pregnant women are insufficient to inform drug-associated risk of adverse developmental outcomes. In an embryo-fetal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of secukinumab during organogenesis at doses up to 30 times the maximum recommended human dose (MRHD) (see Data).The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.DataAnimal DataAn embryo-fetal development study was performed in cynomolgus monkeys with secukinumab. No malformations or embryo-fetal toxicity were observed in fetuses from pregnant monkeys that were administered secukinumab weekly by the subcutaneous route during the period of organogenesis at doses up to 30 times the MRHD (on mg/kg basis at maternal dose of 150 mg/kg).A pre- and post-natal development toxicity study was performed in mice with murine analog of secukinumab. No treatment-related effects on functional, morphological or immunological development were observed in fetuses from pregnant mice that were administered the murine analog of secukinumab on gestation days 6, 11, and 17 and on postpartum days 4, 10, and 16 at doses up to 150 mg/kg/dose.

RECENT MAJOR CHANGES SECTION.

Indications and Usage (1.1)5/2021Indications and Usage (1.2, 1.5)12/2021Dosage and Administration (2.1, 2.2, 2.6)5/2021Dosage and Administration (2.3, 2.6)12/2021Warnings and Precautions (5.1)5/2021.

SPL MEDGUIDE SECTION.

This Medication Guide has been approved by the U.S. Food and Drug Administration.Revised: December 2021Medication GuideCOSENTYX(R) (koe-sen-tix)(secukinumab)injection, for subcutaneous useWhat is the most important information should know about COSENTYXCOSENTYX is medicine that affects your immune system. COSENTYX may increase your risk of having serious side effects such as:Infections. COSENTYX may lower the ability of your immune system to fight infections and may increase your risk of infections.Your healthcare provider should check you for tuberculosis (TB) before starting treatment with COSENTYX.If your healthcare provider feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with COSENTYX and during treatment with COSENTYX.Your healthcare provider should watch you closely for signs and symptoms of TB during treatment with COSENTYX. Do not take COSENTYX if you have an active TB infection. Before starting COSENTYX, tell your healthcare provider if you:are being treated for an infectionhave an infection that does not go away or that keeps coming backhave TB or have been in close contact with someone with TBthink you have an infection or have symptoms of an infection such as: fever, sweats, or chills muscle aches cough shortness of breath blood in your phlegm weight loss warm, red, or painful skin or sores on your body diarrhea or stomach pain burning when you urinate or urinate more often than normalAfter starting COSENTYX, call your healthcare provider right away if you have any of the signs of infection listed above. Do not use COSENTYX if you have any signs of infection unless you are instructed to by your healthcare provider.See What are the possible side effects of COSENTYX for more information about side effects.What is COSENTYXCOSENTYX is prescription medicine used to treat:people years of age and older with moderate to severe plaque psoriasis that involves large areas or many areas of the body, and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light alone or with systemic therapy)people years of age and older with active psoriatic arthritisadults with active ankylosing spondylitisadults with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective signs of inflammationpeople years of age and older with active enthesitis-related arthritisCOSENTYX may improve your psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis, and enthesitis-related arthritis, but it may also lower the ability of your immune system to fight infections.It is not known if COSENTYX is safe and effective in children:below years of age with plaque psoriasisbelow years of age and weighing less than 33 pounds Do not take COSENTYX if you:have had severe allergic reaction to secukinumab or any of the other ingredients in COSENTYX. See the end of this Medication Guide for complete list of ingredients in COSENTYX.Before taking COSENTYX, tell your healthcare provider about all of your medical conditions, including if you: have any of the conditions or symptoms listed in the section What is the most important information should know about COSENTYX have inflammatory bowel disease (Crohns disease or ulcerative colitis).are allergic to latex. The needle cap on the COSENTYX Sensoready(R) 150 mg/mL pen, 150 mg/mL and 75 mg/0.5 mL prefilled syringes contains latex.have recently received or are scheduled to receive an immunization (vaccine). People who take COSENTYX should not receive live vaccines. Children should be brought up to date with all vaccines before starting COSENTYX.are pregnant or plan to become pregnant. It is not known if COSENTYX can harm your unborn baby. You and your healthcare provider should decide if you will use COSENTYX.are breastfeeding or plan to breastfeed. It is not known if COSENTYX passes into your breast milk.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.Know the medicines you take. Keep list of your medicines to show your healthcare provider and pharmacist when you get new medicine. How should use COSENTYXSee the detailed Instructions for Use that comes with your COSENTYX for information on how to prepare and inject dose of COSENTYX, and how to properly throw away (dispose of) used COSENTYX Sensoready pen and prefilled syringes.Use COSENTYX exactly as prescribed by your healthcare provider.COSENTYX comes in single-dose Sensoready pen or single-dose prefilled syringes that you or your caregiver may use at home to give injections. Your healthcare provider will decide which type of COSENTYX is best for you to use at home.If your healthcare provider decides that you or caregiver may give your injections of COSENTYX at home, you should receive training on the right way to prepare and inject COSENTYX. Do not try to inject COSENTYX yourself, until you or your caregiver has been shown how to inject COSENTYX by your healthcare provider. Children should not inject themselves with the Sensoready pen or the prefilled syringes. An adult caregiver should prepare and inject COSENTYX after receiving training on the right way to prepare and inject COSENTYX.Your healthcare provider will prescribe the dose of COSENTYX that is right for you or your child based on their body weight.If your prescribed dose of COSENTYX is 75 mg, you must give injection of COSENTYX 75 mg/0.5 mL for each dose.If your prescribed dose of COSENTYX is 150 mg, you must give injection of COSENTYX 150 mg/mL for each dose.If your prescribed dose of COSENTYX is 300 mg, you must give injections of COSENTYX 150 mg/mL for each dose. COSENTYX is given as an injection under your skin (subcutaneous injection), in your upper legs (thighs) or stomach-area (abdomen) by you or caregiver. caregiver may also give you an injection of COSENTYX in your upper outer arm.Do not give an injection in an area of the skin that is tender, bruised, red or hard, or in an area of skin that is affected by psoriasis.Each injection should be given at different site. Do not use the 2-inch area around your navel (belly button).If you inject more COSENTYX than prescribed, call your healthcare provider or go to the nearest emergency room right away.What are the possible side effects of COSENTYXCOSENTYX may cause serious side effects including:See What is the most important information should know about COSENTYX Inflammatory bowel disease. New cases of inflammatory bowel disease or flare-ups can happen with COSENTYX, and can sometimes be serious. If you have inflammatory bowel disease (ulcerative colitis or Crohns disease), tell your healthcare provider if you have worsening disease symptoms during treatment with COSENTYX or develop new symptoms of stomach pain or diarrhea.Serious allergic reactions. Get emergency medical help right away if you get any of the following symptoms of serious allergic reaction: feel faint swelling of your face, eyelids, lips, mouth, tongue, or throat trouble breathing or throat tightness chest tightness skin rash hives (red, itchy bumps)If you have severe allergic reaction, do not give another injection of COSENTYX.The most common side effects of COSENTYX include: cold symptoms diarrhea upper respiratory infectionsThese are not all of the possible side effects of COSENTYX.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store COSENTYXStore COSENTYX in refrigerator, between 36F to 46F (2C to 8C).Keep COSENTYX in the original carton until ready for use to protect from light.COSENTYX Sensoready pen and COSENTYX 150 mg/mL prefilled syringe may be stored at room temperature, up to 86F (30C), for up to days.Write the date COSENTYX Sensoready pen or COSENTYX 150 mg/mL prefilled syringe was removed from the refrigerator in the space provided on the carton.If unused and not stored above 30C (86F), COSENTYX Sensoready pen and 150 mg/mL prefilled syringe may be returned to the refrigerator.Throw away COSENTYX Sensoready pen or COSENTYX 150 mg/mL prefilled syringe if it has been kept outside of the refrigerator and not been used in over days.Do not freeze COSENTYX.Do not shake COSENTYX.Throw away (dispose of) any unused COSENTYX Sensoready pen or prefilled syringes.Keep COSENTYX and all medicines out of the reach of children.General information about the safe and effective use of COSENTYX.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. Do not use COSENTYX for condition for which it was not prescribed. Do not give COSENTYX to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about COSENTYX that is written for health professionals.What are the ingredients in COSENTYXActive ingredient: secukinumab. Inactive ingredients: Sensoready pen and prefilled syringe: L-histidine/histidine hydrochloride monohydrate, L-methionine, polysorbate 80, trehalose dihydrate, and sterile water for injection. Vial: L-histidine/histidine hydrochloride monohydrate, polysorbate 80, and sucrose. Manufactured by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936For more information, call 1-888-669-6682 or go to www.COSENTYX.com T2021-163. Your healthcare provider should check you for tuberculosis (TB) before starting treatment with COSENTYX.. If your healthcare provider feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with COSENTYX and during treatment with COSENTYX.. Your healthcare provider should watch you closely for signs and symptoms of TB during treatment with COSENTYX. Do not take COSENTYX if you have an active TB infection. are being treated for an infection. have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. think you have an infection or have symptoms of an infection such as:. people years of age and older with moderate to severe plaque psoriasis that involves large areas or many areas of the body, and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light alone or with systemic therapy). people years of age and older with active psoriatic arthritis. adults with active ankylosing spondylitis. adults with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective signs of inflammation. people years of age and older with active enthesitis-related arthritis. below years of age with plaque psoriasis. below years of age and weighing less than 33 pounds. have had severe allergic reaction to secukinumab or any of the other ingredients in COSENTYX. See the end of this Medication Guide for complete list of ingredients in COSENTYX.. have inflammatory bowel disease (Crohns disease or ulcerative colitis).. are allergic to latex. The needle cap on the COSENTYX Sensoready(R) 150 mg/mL pen, 150 mg/mL and 75 mg/0.5 mL prefilled syringes contains latex.. have recently received or are scheduled to receive an immunization (vaccine). People who take COSENTYX should not receive live vaccines. Children should be brought up to date with all vaccines before starting COSENTYX.. are pregnant or plan to become pregnant. It is not known if COSENTYX can harm your unborn baby. You and your healthcare provider should decide if you will use COSENTYX.. are breastfeeding or plan to breastfeed. It is not known if COSENTYX passes into your breast milk.. Use COSENTYX exactly as prescribed by your healthcare provider.. COSENTYX comes in single-dose Sensoready pen or single-dose prefilled syringes that you or your caregiver may use at home to give injections. Your healthcare provider will decide which type of COSENTYX is best for you to use at home.. If your healthcare provider decides that you or caregiver may give your injections of COSENTYX at home, you should receive training on the right way to prepare and inject COSENTYX. Do not try to inject COSENTYX yourself, until you or your caregiver has been shown how to inject COSENTYX by your healthcare provider. Children should not inject themselves with the Sensoready pen or the prefilled syringes. An adult caregiver should prepare and inject COSENTYX after receiving training on the right way to prepare and inject COSENTYX.. Your healthcare provider will prescribe the dose of COSENTYX that is right for you or your child based on their body weight.If your prescribed dose of COSENTYX is 75 mg, you must give injection of COSENTYX 75 mg/0.5 mL for each dose.If your prescribed dose of COSENTYX is 150 mg, you must give injection of COSENTYX 150 mg/mL for each dose.If your prescribed dose of COSENTYX is 300 mg, you must give injections of COSENTYX 150 mg/mL for each dose. If your prescribed dose of COSENTYX is 75 mg, you must give injection of COSENTYX 75 mg/0.5 mL for each dose.. If your prescribed dose of COSENTYX is 150 mg, you must give injection of COSENTYX 150 mg/mL for each dose.. If your prescribed dose of COSENTYX is 300 mg, you must give injections of COSENTYX 150 mg/mL for each dose.. COSENTYX is given as an injection under your skin (subcutaneous injection), in your upper legs (thighs) or stomach-area (abdomen) by you or caregiver. caregiver may also give you an injection of COSENTYX in your upper outer arm.. Do not give an injection in an area of the skin that is tender, bruised, red or hard, or in an area of skin that is affected by psoriasis.. Each injection should be given at different site. Do not use the 2-inch area around your navel (belly button).. If you inject more COSENTYX than prescribed, call your healthcare provider or go to the nearest emergency room right away.. See What is the most important information should know about COSENTYX Inflammatory bowel disease. New cases of inflammatory bowel disease or flare-ups can happen with COSENTYX, and can sometimes be serious. If you have inflammatory bowel disease (ulcerative colitis or Crohns disease), tell your healthcare provider if you have worsening disease symptoms during treatment with COSENTYX or develop new symptoms of stomach pain or diarrhea.. Serious allergic reactions. Get emergency medical help right away if you get any of the following symptoms of serious allergic reaction:. Store COSENTYX in refrigerator, between 36F to 46F (2C to 8C).. Keep COSENTYX in the original carton until ready for use to protect from light.. COSENTYX Sensoready pen and COSENTYX 150 mg/mL prefilled syringe may be stored at room temperature, up to 86F (30C), for up to days.. Write the date COSENTYX Sensoready pen or COSENTYX 150 mg/mL prefilled syringe was removed from the refrigerator in the space provided on the carton.. If unused and not stored above 30C (86F), COSENTYX Sensoready pen and 150 mg/mL prefilled syringe may be returned to the refrigerator.. Throw away COSENTYX Sensoready pen or COSENTYX 150 mg/mL prefilled syringe if it has been kept outside of the refrigerator and not been used in over days.. Do not freeze COSENTYX.. Do not shake COSENTYX.. Throw away (dispose of) any unused COSENTYX Sensoready pen or prefilled syringes.

SPL UNCLASSIFIED SECTION.

1.1 Plaque Psoriasis. COSENTYX(R) is indicated for the treatment of moderate to severe plaque psoriasis in patients years and older who are candidates for systemic therapy or phototherapy.

STORAGE AND HANDLING SECTION.

16.2 Storage and Handling. Refrigerate COSENTYX Sensoready pens, prefilled syringes, and vials at 2oC to 8oC (36oF to 46oF). Keep the product in the original carton to protect from light until the time of use. Do not freeze. To avoid foaming do not shake. COSENTYX does not contain preservative; discard any unused portion.If necessary, COSENTYX Sensoready pens and 150 mg/mL prefilled syringes may be stored for up to days at room temperature not to exceed 30C (86F). Write the date COSENTYX was removed from the refrigerator in the space provided on the carton. If unused and not stored above 30C (86F), COSENTYX Sensoready pens and 150 mg/mL prefilled syringes may be returned to the refrigerator. Throw away COSENTYX if it has been kept outside of the refrigerator and not been used in over days.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryLimited available human data with COSENTYX use in pregnant women are insufficient to inform drug-associated risk of adverse developmental outcomes. In an embryo-fetal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of secukinumab during organogenesis at doses up to 30 times the maximum recommended human dose (MRHD) (see Data).The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.DataAnimal DataAn embryo-fetal development study was performed in cynomolgus monkeys with secukinumab. No malformations or embryo-fetal toxicity were observed in fetuses from pregnant monkeys that were administered secukinumab weekly by the subcutaneous route during the period of organogenesis at doses up to 30 times the MRHD (on mg/kg basis at maternal dose of 150 mg/kg).A pre- and post-natal development toxicity study was performed in mice with murine analog of secukinumab. No treatment-related effects on functional, morphological or immunological development were observed in fetuses from pregnant mice that were administered the murine analog of secukinumab on gestation days 6, 11, and 17 and on postpartum days 4, 10, and 16 at doses up to 150 mg/kg/dose.. 8.2 Lactation. Risk SummaryIt is not known whether secukinumab is excreted in human milk or absorbed systemically after ingestion. There are no data on the effects of COSENTYX on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for COSENTYX and any potential adverse effects on the breastfed child from COSENTYX or from the underlying maternal condition.. 8.4 Pediatric Use. The safety and effectiveness of COSENTYX have been established in pediatric subjects aged years and older with moderate to severe plaque psoriasis [see Adverse Reactions (6.1), Clinical Studies (14.2)]. Safety and effectiveness of COSENTYX in pediatric patients with plaque psoriasis below the age of years have not been established.The safety and effectiveness of COSENTYX have been established in patients weighing 15 kg or more with JPsA (2 years and older) and ERA (4 years and older) [see Adverse Reactions (6.1), Clinical Studies (14.6)].The safety and effectiveness of COSENTYX in pediatric patients below the age of years and with body weight less than 15 kg have not been established.. 8.5 Geriatric Use. Of the 3430 plaque psoriasis subjects exposed to COSENTYX in clinical trials, total of 230 were 65 years or older, and 32 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 years and older was not sufficient to determine whether they responded differently from younger subjects.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Infections: Serious infections have occurred. Caution should be exercised when considering the use of COSENTYX in patients with chronic infection or history of recurrent infection. If serious infection develops, discontinue COSENTYX until the infection resolves. (5.1)Tuberculosis (TB): Prior to initiating treatment with COSENTYX, evaluate for TB. (5.2)Inflammatory Bowel Disease: Cases of inflammatory bowel disease were observed in clinical trials. Caution should be exercised when prescribing COSENTYX to patients with inflammatory bowel disease. (5.3)Hypersensitivity Reactions: If an anaphylactic reaction or other serious allergic reaction occurs, discontinue COSENTYX immediately and initiate appropriate therapy. (5.4)Immunizations: Avoid use of live vaccines in patients treated with COSENTYX. (5.6). Infections: Serious infections have occurred. Caution should be exercised when considering the use of COSENTYX in patients with chronic infection or history of recurrent infection. If serious infection develops, discontinue COSENTYX until the infection resolves. (5.1). Tuberculosis (TB): Prior to initiating treatment with COSENTYX, evaluate for TB. (5.2). Inflammatory Bowel Disease: Cases of inflammatory bowel disease were observed in clinical trials. Caution should be exercised when prescribing COSENTYX to patients with inflammatory bowel disease. (5.3). Hypersensitivity Reactions: If an anaphylactic reaction or other serious allergic reaction occurs, discontinue COSENTYX immediately and initiate appropriate therapy. (5.4). Immunizations: Avoid use of live vaccines in patients treated with COSENTYX. (5.6). 5.1 Infections. COSENTYX may increase the risk of infections. In clinical trials, higher rate of infections was observed in COSENTYX treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials in subjects with moderate to severe plaque psoriasis, higher rates of common infections, such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed with COSENTYX compared with placebo. similar increase in risk of infection was seen in placebo-controlled trials in subjects with PsA, AS and nr-axSpA. The incidence of some types of infections appeared to be dose-dependent in clinical studies [see Adverse Reactions (6.1)]. In the postmarketing setting, serious and some fatal infections have been reported in patients receiving COSENTYX.Exercise caution when considering the use of COSENTYX in patients with chronic infection or history of recurrent infection.Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If patient develops serious infection, monitor the patient closely and discontinue COSENTYX until the infection resolves.. 5.2 Pre-Treatment Evaluation for Tuberculosis. Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Avoid administration of COSENTYX to patients with active TB infection. Initiate treatment of latent TB prior to administering COSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX in patients with past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients closely for signs and symptoms of active TB during and after treatment.. 5.3 Inflammatory Bowel Disease. Caution should be used when prescribing COSENTYX to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in COSENTYX treated subjects during clinical trials in plaque psoriasis, PsA, AS and nr-axSpA. In addition, new onset inflammatory bowel disease cases occurred in clinical trials with COSENTYX. In an exploratory trial in 59 subjects with active Crohns disease, there were trends toward greater disease activity and increased adverse events in the secukinumab group as compared to the placebo group. Patients who are treated with COSENTYX should be monitored for signs and symptoms of inflammatory bowel disease [see Adverse Reactions (6.1)].. 5.4 Hypersensitivity Reactions. Anaphylaxis and cases of urticaria occurred in COSENTYX treated subjects in clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated [see Contraindications (4), Adverse Reactions (6.1)]. 5.5 Risk of Hypersensitivity in Latex-Sensitive Individuals. The removable caps of the COSENTYX Sensoready pen and the COSENTYX mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals. The safe use of COSENTYX Sensoready pen or prefilled syringe in latex-sensitive individuals has not been studied.. 5.6 Immunizations. Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. COSENTYX may alter patients immune response to live vaccines. Avoid use of live vaccines in patients treated with COSENTYX [see Clinical Pharmacology (12.2)].

POSTMARKETING EXPERIENCE SECTION.

6.3 Postmarketing Experience. The following adverse reactions have been reported during postapproval use of COSENTYX. Because they are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Skin and Subcutaneous Tissue Disorders: Eczematous eruptions (atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma) [see Warnings and Precautions (5.5)].