Secukinumab

11 DESCRIPTION Secukinumab, a recombinant human monoclonal IgG1/κ antibody, is an interleukin-17A antagonist. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line. Secukinumab has a molecular mass of approximately 151 kDa; both heavy chains of secukinumab contain oligosaccharide chains. COSENTYX Injection for Subcutaneous Use COSENTYX injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for subcutaneous use. COSENTYX injection is supplied in a single-dose UnoReady pen (300 mg/2 mL) with a 27-gauge fixed ½-inch needle, a single-dose Sensoready pen with a 27-gauge fixed ½-inch needle, or a single-dose prefilled syringe (300 mg/2 mL, 150 mg/mL, 75 mg/0.5 mL) with a 27-gauge fixed ½-inch needle. The removable cap of the COSENTYX Sensoready pen and prefilled syringes (150 mg/mL, 75 mg/0.5 mL) contains natural rubber latex. Each COSENTYX UnoReady pen or prefilled syringe (300 mg/2 mL) contains 300 mg of secukinumab formulated in: L-histidine/histidine hydrochloride monohydrate (6.206 mg), L-methionine (1.492 mg), polysorbate 80 (0.4 mg), trehalose dihydrate (151.34 mg), and Sterile Water for Injection, USP, at pH of 5.8. Each COSENTYX Sensoready pen or prefilled syringe (150 mg/mL) 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 prefilled syringe (75 mg/0.5 mL) 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 Injection for Intravenous Use COSENTYX solution is supplied as a sterile, preservative free, clear to opalescent, colorless to slightly yellowish solution in single-dose vials for intravenous infusion after dilution. Each COSENTYX vial (125 mg/5 mL) contains 125 mg of secukinumab formulated in: L-histidine (5.67 mg), L-histidine hydrochloride monohydrate (13.3 mg), L-methionine (3.73 mg), polysorbate 80 (1 mg), trehalose dihydrate (426 mg), and Sterile Water for Injection, USP, at pH of 5.8.

1 INDICATIONS AND USAGE COSENTYX is a human interleukin-17A antagonist indicated for the treatment of: moderate to severe plaque psoriasis (PsO) in adults and pediatric patients 6 years and older who are candidates for systemic therapy or phototherapy. ( 1.1 ) active psoriatic arthritis (PsA) in adults and pediatric patients 2 years of age and older. ( 1.2 ) active ankylosing spondylitis (AS) in adults and pediatric patients 12 years of age and older. ( 1.3 ) active non-radiographic axial spondyloarthritis (nr-axSpA) in adults with objective signs of inflammation. ( 1.4 ) active enthesitis-related arthritis (ERA) in pediatric patients 4 years of age and older. ( 1.5 ) moderate to severe hidradenitis suppurativa (HS) in adults and pediatric patients 12 years of age and older. ( 1.6 ) 1.1 Plaque Psoriasis COSENTYX ® is indicated for the treatment of moderate to severe plaque psoriasis (PsO) in adults and pediatric patients 6 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 adults and pediatric patients 2 years of age and older. 1.3 Ankylosing Spondylitis COSENTYX is indicated for the treatment of active ankylosing spondylitis (AS) in adults and pediatric patients 12 years of age and older. 1.4 Non-Radiographic Axial Spondyloarthritis COSENTYX is indicated for the treatment of active non-radiographic axial spondyloarthritis (nr-axSpA) in adult patients with objective signs of inflammation. 1.5 Enthesitis-Related Arthritis COSENTYX is indicated for the treatment of active enthesitis-related arthritis (ERA) in pediatric patients 4 years of age and older. 1.6 Hidradenitis Suppurativa COSENTYX is indicated for the treatment of moderate to severe hidradenitis suppurativa (HS) in adults and pediatric patients 12 years of age and older.

5 WARNINGS AND PRECAUTIONS Infections : Serious infections have occurred. Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. If a serious infection develops, discontinue COSENTYX until the infection resolves. ( 5.1 ) Hypersensitivity Reactions : If an anaphylactic reaction or other serious allergic reaction occurs, discontinue COSENTYX immediately and initiate appropriate therapy. ( 5.2 ) Tuberculosis (TB) : Prior to initiating treatment with COSENTYX, evaluate for TB. ( 5.3 ) Inflammatory Bowel Disease (IBD) : Cases of IBD were observed in clinical trials. Exercise caution when prescribing COSENTYX to patients with IBD. ( 5.4 ) Eczematous Eruptions : Cases of severe eczematous eruptions have occurred in patients receiving COSENTYX. ( 5.5 ) Immunizations : Avoid use of live vaccines in patients treated with COSENTYX. ( 5.7 ) 5.1 Infections COSENTYX may increase the risk of infections. In clinical trials, a 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 PsO, 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 in subjects treated with COSENTYX compared to placebo-treated subjects. A similar increase in risk of infection in subjects treated with COSENTYX was seen in placebo-controlled trials in subjects with PsA, AS and nr-axSpA. The incidence of some types of infections, including fungal infections, appeared to be dose-dependent in clinical trials [see Adverse Reactions (6.1)] . In the postmarketing setting, serious bacterial, viral, and fungal opportunistic infections, and some fatal infections have been reported in patients receiving IL-17 inhibitors including COSENTYX. Cases of Hepatitis B virus reactivation have been reported [see Adverse Reactions (6.2)] . Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, monitor the patient closely and discontinue COSENTYX until the infection resolves. If signs of Hepatitis B virus reactivation occur, consult a hepatitis specialist. COSENTYX is not recommended for use in patients with active viral hepatitis. 5.2 Hypersensitivity Reactions Serious hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in COSENTYX treated subjects in clinical trials and in the post-marketing setting [see Adverse Reactions (6.1, 6.2)] . If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of COSENTYX and initiate appropriate therapy [see Contraindications (4)] . 5.3 Pre-Treatment Evaluation for Tuberculosis Evaluate patients for active or latent 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 a 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. In the postmarketing setting, cases were reported where patients with a history of latent tuberculosis (TB) who were treated with COSENTYX developed active TB. 5.4 Inflammatory Bowel Disease Inflammatory Bowel Disease (IBD) exacerbations, in some cases serious and/or leading to discontinuation of COSENTYX, occurred in COSENTYX treated subjects during clinical trials in PsO, PsA, AS, nr-axSpA, and HS. In adult subjects with HS, the incidence of IBD was higher in subjects who received COSENTYX 300 mg every 2 weeks (Ulcerative Colitis [UC] 1 case, EAIR 0.2/100 subject-years; Crohn`s Disease [CD] 1 case, EAIR 0.2/100 subject-years) compared to subjects who received COSENTYX 300 mg every 4 weeks (IBD 1 case, EAIR 0.2/100 subject-years). In addition, new onset IBD cases occurred in subjects treated with COSENTYX in clinical trials. In an exploratory trial in 59 subjects with active Crohn’s disease [COSENTYX is not approved for the treatment of Crohn`s disease], there were trends toward greater disease activity and increased adverse reactions in subjects treated with COSENTYX as compared to placebo-treated subjects. Exercise caution when prescribing COSENTYX to patients with IBD. Patients treated with COSENTYX should be monitored for signs and symptoms of IBD [see Adverse Reactions (6.1)] . 5.5 Eczematous Eruptions In postmarketing reports, cases of severe eczematous eruptions, including atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma, were reported in patients receiving COSENTYX; some cases resulted in hospitalization. The onset of eczematous eruptions was variable, ranging from days to months after the first dose of COSENTYX. Treatment may need to be discontinued to resolve the eczematous eruption. Some patients were successfully treated for eczematous eruptions while continuing COSENTYX. 5.6 Risk of Hypersensitivity in Latex-Sensitive Individuals The removable cap of the COSENTYX Sensoready pen and prefilled syringes (150 mg/mL, 75 mg/0.5 mL) contains natural rubber latex, which may cause a hypersensitivity reaction in latex-sensitive individuals. The safe use of the COSENTYX Sensoready pen or prefilled syringes (150 mg/mL, 75 mg/0.5 mL) in latex-sensitive individuals has not been studied. 5.7 Immunizations Prior to initiating therapy with COSENTYX, consider completion of all age-appropriate immunizations according to current immunization guidelines. COSENTYX may alter a patient’s immune response to live vaccines. Avoid use of live vaccines in patients treated with COSENTYX [see Clinical Pharmacology (12.2)] .

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail elsewhere in the labeling: Infections [see Warnings and Precautions (5.1)] Hypersensitivity Reactions [see Warnings and Precautions (5.2)] Inflammatory Bowel Disease [see Warnings and Precautions (5.4)] Eczematous Eruptions [see Warnings and Precautions (5.5)] 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 a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Clinical Trials of Subcutaneous COSENTYX Adverse Reactions from Clinical Trials in Adults with PsO A total of 3,430 adult subjects with PsO were treated with COSENTYX in controlled and uncontrolled clinical trials. Of these, 1,641 subjects were treated with COSENTYX for at least 1 year. Four placebo-controlled Phase 3 trials in PsO subjects (Trials PsO1, PsO2, PsO3, and PsO4) were pooled to evaluate the safety of COSENTYX in comparison to placebo up to 12 weeks after treatment initiation. In total, 2,077 subjects were evaluated (691 in the COSENTYX 300 mg group, 692 in the COSENTYX 150 mg group, and 694 in the placebo group). Subjects randomized to COSENTYX received 300 mg or 150 mg doses subcutaneously at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks [see Clinical Studies (14)] . Table 2 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the COSENTYX groups than the placebo group during the 12-week placebo-controlled period of these trials. Table 2: Adverse Reactions Reported by Greater Than 1% of Adult Subjects With PsO (and at a Higher Rate in Subjects Treated with COSENTYX) Through Week 12 in Trials PsO1, PsO2, PsO3, and PsO4 COSENTYX Adverse reactions 300 mg (N = 691) n (%) 150 mg (N = 692) n (%) Placebo (N = 694) n (%) Nasopharyngitis 79 (11.4) 85 (12.3) 60 (8.6) Diarrhea 28 (4.1) 18 (2.6) 10 (1.4) Upper respiratory tract infection 17 (2.5) 22 (3.2) 5 (0.7) Rhinitis 10 (1.4) 10 (1.4) 5 (0.7) Oral herpes 9 (1.3) 1 (0.1) 2 (0.3) Pharyngitis 8 (1.2) 7 (1.0) 0 (0) Urticaria 4 (0.6) 8 (1.2) 1 (0.1) Rhinorrhea 8 (1.2) 2 (0.3) 1 (0.1) Adverse reactions that occurred in subjects treated with COSENTYX 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, IBD, increased liver transaminases, and neutropenia. Infections In the placebo-controlled period of the clinical trials in PsO (a total of 1,382 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. Over the entire treatment period (a total of 3,430 PsO 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 subject-year of follow-up) and serious infections were reported in 1.2% of subjects treated with COSENTYX (0.015 per subject-year of follow-up). Phase 3 data showed an increasing trend for some types of infection with increasing serum secukinumab concentrations. Candida infections, herpes viral infections, staphylococcal skin infections, and infections requiring treatment increased as serum secukinumab concentration increased. In the PsO open-label extension of Trials PsO1 and PsO2 (median follow-up of 3.9 years), representing 3,582 subject-years of exposure, 74% of COSENTYX treated subjects reported infections (55 per 100 subject-years) and serious infections were reported in 4.5% of COSENTYX treated subjects (1.4 per 100 subject-years). Sepsis was reported in 5 COSENTYX treated subjects (0.2 per 100 subject-years). Neutropenia was observed in controlled portion of clinical trials. Most cases of COSENTYX 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 x 10 9 /L) was reported in 1% of COSENTYX treated subjects (0.3 per 100 subject-years). Some cases of serious infections were associated with neutropenia; however, the causal relationship was not established. Inflammatory Bowel Disease Cases of IBD, in some cases serious, were observed in subjects treated with COSENTYX in clinical trials. In the PsO program, with 3,430 subjects exposed to COSENTYX over the entire treatment period for up to 52 weeks (2,725 subject-years), there were 3 cases (0.11 per 100 subject-years) of exacerbation of CD, 2 cases (0.08 per 100 subject-years) of exacerbation of UC, and 2 cases (0.08 per 100 subject-years) of new onset UC. There were no IBD cases in placebo-treated subjects (N = 793; 176 subject-years) during the 12-week placebo-controlled period. One case of exacerbation of Crohn’s disease in a subject treated with COSENTYX subject was reported in open-label portions of clinical trials in PsO. Adverse Reactions from Clinical Trials in Pediatric Subjects with PsO The safety of COSENTYX was assessed in two Phase 3 trials in pediatric subjects with PsO. The first was a randomized, double-blind, placebo and active-controlled, 236-week trial (Trial PsO8) that enrolled 162 pediatric subjects 6 years of age and older, with severe PsO (defined by PASI score ≥ 20, an IGA modified 2011 score of 4, and involving ≥ 10% of the body surface area [BSA]) who were candidates for systemic therapy. The 162 subjects were randomized to receive placebo, a biologic active control, or COSENTYX. In the COSENTYX groups, subjects with body weight (BW) less than 25 kg received 75 mg, subjects with BW 25 to less than 50 kg received either 75 mg or 150 mg (2 times the recommended dose), and subjects with BW of at least 50 kg received either 150 mg or 300 mg (2 times the recommended dose). Subjects were dosed at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. The second trial was a randomized, open-label, 208-week trial (Trial PsO9; NCT03668613) of 84 pediatric subjects 6 years of age and older with moderate to severe PsO (defined by a 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 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]. Subjects were dosed at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. The safety profile of COSENTYX reported in these trials was consistent with the safety profile reported in adult PsO trials. Infections One case of methicillin-resistant Staphylococcus aureus (MRSA) toxic shock syndrome (TSS) was reported in a COSENTYX treated pediatric 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 subject-years)], 22 (11%) subjects reported ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 neutropenia (≥ 1,000 to < 1,500 cells/mm 3 ) 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 a total of 80 pediatric subjects treated with COSENTYX and 41 subjects treated with placebo up to 12 weeks, ≥ CTCAE Grade 2 neutropenia was reported in 3 (4%) of the subjects treated with COSENTYX compared with no subjects treated with placebo. No serious infections were associated with cases of neutropenia. Adverse Reactions from Clinical Trials in Adults with PsA COSENTYX was studied in two placebo-controlled PsA trials with 1,003 adult patients (703 patients on COSENTYX and 300 patients on placebo). Of the 703 patients who received COSENTYX, 299 patients received a 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 4 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 a proportion of at least 2% and at a 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 adult patients with PsA treated with COSENTYX is consistent with the safety profile in the PsO trials in adults. Similar to the clinical trials in patients with PsO, there was an increased proportion of patients with infections in the COSENTYX groups (29%) compared to placebo group (26%). There were cases of CD and UC in the secukinumab group that included patients who experienced either exacerbations or the development of new disease. There were three cases of IBD, of which two patients received secukinumab and one received placebo. Adverse Reactions from Clinical Trials in Adults with AS COSENTYX was studied in two placebo-controlled AS trials with 590 adult patients (394 patients on COSENTYX and 196 patients on placebo). Of the 394 patients who received COSENTYX, 145 patients received a 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 4 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 a proportion of at least 2% and at a 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 AS treated with COSENTYX is consistent with the safety profile in PsO clinical trials. In a third controlled trial 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 PsO, 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 8 cases of IBD during the entire treatment period [5 cases of Crohn’s (0.7 per 100 patient-years) and 3 cases of UC (0.4 per 100 patient-years)]. During the placebo-controlled 16-week period, there were 2 Crohn’s disease exacerbations and 1 new onset UC case that was a serious adverse event in patients treated with COSENTYX compared to none of the patients treated with placebo. During the remainder of the trial when all patients received COSENTYX, 1 patient developed Crohn’s disease, 2 patients had Crohn’s exacerbations, 1 patient developed UC, and 1 patient had an UC exacerbation. Adverse Reactions from Clinical Trials in Adults with nr-axSpA COSENTYX was studied in one randomized, double-blind, placebo-controlled nr-axSpA trial with 555 adult patients (185 patients received a loading COSENTYX dose, 184 patients did not receive a loading COSENTYX dose, and 186 patients received 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 trial 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 versus 72 per 100 patient-years), including nasopharyngitis, upper respiratory tract infection and urinary tract infection, and gastrointestinal disorders (27 per 100 patient-years versus 22 per 100 patient-years), including gastritis, lower abdominal pain, colitis, diarrhea, and hematochezia. Adverse Reactions from Clinical Trials in Pediatric Patients with Juvenile Psoriatic Arthritis (JPsA) and ERA COSENTYX was studied in one double-blind, placebo-controlled, event-driven, randomized trial in 86 pediatric patients aged 2 to less than 18 years old with JPsA and ERA. The safety profile reported in this trial was consistent with the safety profile of secukinumab. Adverse Reactions from Clinical Trials in Adults with HS COSENTYX was studied in two 52-week, randomized, double-blind, placebo-controlled HS trials with 1,084 adult subjects (361 subjects received COSENTYX 300 mg every 2 weeks, 360 subjects received COSENTYX 300 mg every 4 weeks, and 363 subjects received placebo) with a total of 901 subject-years of COSENTYX exposure (the median duration of exposure for subjects treated with COSENTYX was 360 days). The safety profile of COSENTYX observed in these HS trials was consistent with the known safety profile of COSENTYX observed in the PsO trials. Infections During the 16-week placebo-controlled period, subjects who received COSENTYX 300 mg every 2 weeks had the highest incidence of fungal infections (5.3%), compared to subjects who received COSENTYX 300 mg every 4 weeks (4.2%) and subjects who received placebo (2.8%). With longer exposure, the rate of fungal infections remained higher for subjects who received COSENTYX 300 mg every 2 weeks (14.7/100 subject-years) compared to subjects who received COSENTYX 300 mg every 4 weeks (10.1/100 subject-years). The majority of the cases were reported as non-serious, non-severe, and resolved with anti-fungal treatment. Inflammatory Bowel Disease In the open-labeled portion of HS clinical trials, five (0.7%) IBD adverse reactions were reported, all of which were serious and led to withdrawal of trial drug, and occurred only in subjects treated with COSENTYX 300 mg every 2 weeks. There were no IBD cases in subjects treated with COSENTYX 300 mg every 4 weeks. Adverse Reactions of Intravenous COSENTYX The safety of intravenous COSENTYX is based on the pharmacokinetic exposure and extrapolation of the established safety of subcutaneous COSENTYX in PsA, AS and nr-axSpA patients [see Clinical Pharmacology (12.3)] . 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of COSENTYX. Because they are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders : anaphylaxis, angioedema, systemic vasculitis Skin and subcutaneous tissue disorders : eczematous eruptions (atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma), cutaneous vasculitis, pyoderma gangrenosum Infections : bacterial, viral, and fungal opportunistic infections, including esophageal candidiasis, tracheobronchial candidiasis, cutaneous aspergillosis, cytomegalovirus gastroenteritis/colitis, herpes simplex encephalitis, herpes simplex keratitis, Pneumocystis jiroveci pneumonia, Hepatitis B virus reactivation, histoplasmosis, toxoplasmosis

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Limited available human data with COSENTYX use in pregnant women are insufficient to inform a 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. Data Animal Data An 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 a mg/kg basis at a maternal dose of 150 mg/kg). A pre- and post-natal development toxicity study was performed in mice with a 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 Summary It 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 mother’s 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 Subcutaneous Administration Pediatric Plaque Psoriasis The safety and effectiveness of COSENTYX have been established for the treatment of moderate to severe PsO in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy [see Adverse Reactions (6.1) and Clinical Studies (14.2)] . The safety and effectiveness of COSENTYX in pediatric patients with PsO below the age of 6 years old have not been established. Juvenile Psoriatic Arthritis The safety and effectiveness of COSENTYX have been established for the treatment of active JPsA in pediatric patients aged 2 years and older who weigh 15 kg or more [see Adverse Reactions (6.1) and Clinical Studies (14.6)] . The safety and effectiveness of COSENTYX in pediatric patients with JPsA below the age of 2 years old or with a body weight less than 15 kg have not been established. Juvenile Ankylosing Spondylitis The safety and effectiveness of COSENTYX have been established for treatment of JAS in pediatric patients 12 years of age and older. Use of COSENTYX for this indication is supported by safety and efficacy data from adequate and well-controlled trials in adult subjects with AS. Additional evidence includes pharmacokinetic data from adult subjects with PsO, PsA, and AS and pediatric subjects with PsO, JPsA, and ERA, as well as safety data from clinical trials in pediatric subjects with PsO, JPsA, and ERA. The pharmacokinetics are predicted to be comparable between adult AS and pediatric subjects with JAS [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.4)] . The safety and effectiveness of COSENTYX in pediatric patients with JAS below the age of 12 years old have not been established. Axial Juvenile Spondyloarthritis Six pediatric patients with axial symptoms were participants in a study for JPsA and ERA (NCT03031782). Due to the limited number of patients and uncertainty fulfilling Axial Juvenile Spondyloarthritis (AxJSpA) classification criteria, the effectiveness and safety of COSENTYX in AxJSpA has not been established. Safety was comparable to pediatric patients treated with COSENTYX for JPsA and ERA [see Adverse Reactions (6.1)] . Enthesitis-Related Arthritis The safety and effectiveness of COSENTYX have been established for the treatment of active ERA in pediatric patients aged 4 years and older who weigh 15 kg or more [see Adverse Reactions (6.1) and Clinical Studies (14.6)] . The safety and effectiveness of COSENTYX in pediatric patients with ERA below the age of 4 years old or with body weight less than 15 kg have not been established. Hidradenitis Suppurativa The safety and effectiveness of COSENTYX have been established for the treatment of moderate to severe HS in pediatric patients 12 years of age and older who weigh 30 kg or more. Use of COSENTYX for this indication is supported by safety and efficacy data from adequate and well-controlled trials in adult subjects with moderate to severe HS. Additional evidence includes population pharmacokinetic modeling and simulation based on data from adult subjects with PsO and HS and pediatric subjects with PsO, as well as safety data from clinical trials in pediatric subjects with PsO and JIA (JPsA and ERA) [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.7)] . The safety and effectiveness of COSENTYX in pediatric patients with HS below the age of 12 years old or with a body weight less than 30 kg have not been established. Intravenous Administration The safety and effectiveness of intravenous COSENTYX in pediatric patients have not been established. 8.5 Geriatric Use Of the 3,430 PsO subjects exposed to subcutaneous COSENTYX in clinical trials, a total of 230 (7%) were 65 years of age and older, and 32 (1%) subjects were 75 years of age and older. Although no differences in safety or efficacy were observed between subjects 65 years of age and older and younger adult subjects, the number of subjects 65 years of age and older was not sufficient to determine whether they respond differently from younger adult subjects. Of the 1,060 subjects with HS exposed to COSENTYX in clinical trials, a total of 14 (1.3%) were 65 years of age and older. Clinical trials in HS did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

8.4 Pediatric Use Subcutaneous Administration Pediatric Plaque Psoriasis The safety and effectiveness of COSENTYX have been established for the treatment of moderate to severe PsO in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy [see Adverse Reactions (6.1) and Clinical Studies (14.2)] . The safety and effectiveness of COSENTYX in pediatric patients with PsO below the age of 6 years old have not been established. Juvenile Psoriatic Arthritis The safety and effectiveness of COSENTYX have been established for the treatment of active JPsA in pediatric patients aged 2 years and older who weigh 15 kg or more [see Adverse Reactions (6.1) and Clinical Studies (14.6)] . The safety and effectiveness of COSENTYX in pediatric patients with JPsA below the age of 2 years old or with a body weight less than 15 kg have not been established. Juvenile Ankylosing Spondylitis The safety and effectiveness of COSENTYX have been established for treatment of JAS in pediatric patients 12 years of age and older. Use of COSENTYX for this indication is supported by safety and efficacy data from adequate and well-controlled trials in adult subjects with AS. Additional evidence includes pharmacokinetic data from adult subjects with PsO, PsA, and AS and pediatric subjects with PsO, JPsA, and ERA, as well as safety data from clinical trials in pediatric subjects with PsO, JPsA, and ERA. The pharmacokinetics are predicted to be comparable between adult AS and pediatric subjects with JAS [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.4)] . The safety and effectiveness of COSENTYX in pediatric patients with JAS below the age of 12 years old have not been established. Axial Juvenile Spondyloarthritis Six pediatric patients with axial symptoms were participants in a study for JPsA and ERA (NCT03031782). Due to the limited number of patients and uncertainty fulfilling Axial Juvenile Spondyloarthritis (AxJSpA) classification criteria, the effectiveness and safety of COSENTYX in AxJSpA has not been established. Safety was comparable to pediatric patients treated with COSENTYX for JPsA and ERA [see Adverse Reactions (6.1)] . Enthesitis-Related Arthritis The safety and effectiveness of COSENTYX have been established for the treatment of active ERA in pediatric patients aged 4 years and older who weigh 15 kg or more [see Adverse Reactions (6.1) and Clinical Studies (14.6)] . The safety and effectiveness of COSENTYX in pediatric patients with ERA below the age of 4 years old or with body weight less than 15 kg have not been established. Hidradenitis Suppurativa The safety and effectiveness of COSENTYX have been established for the treatment of moderate to severe HS in pediatric patients 12 years of age and older who weigh 30 kg or more. Use of COSENTYX for this indication is supported by safety and efficacy data from adequate and well-controlled trials in adult subjects with moderate to severe HS. Additional evidence includes population pharmacokinetic modeling and simulation based on data from adult subjects with PsO and HS and pediatric subjects with PsO, as well as safety data from clinical trials in pediatric subjects with PsO and JIA (JPsA and ERA) [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.7)] . The safety and effectiveness of COSENTYX in pediatric patients with HS below the age of 12 years old or with a body weight less than 30 kg have not been established. Intravenous Administration The safety and effectiveness of intravenous COSENTYX in pediatric patients have not been established.