COSENTYX

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.

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. ( 2.2 , 2.11 , 2.12 ) Administration of Intravenous Formulation: COSENTYX for intravenous use must be diluted prior to administration. Administer as an intravenous infusion after dilution over a period of 30 minutes. ( 2.12 ) Plaque Psoriasis: Subcutaneous Dosage in Adults: Recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. For some patients, a dose of 150 mg may be acceptable. ( 2.3 ) Subcutaneous Dosage in Pediatric Patients 6 Years and Older: Recommended weight-based dosage is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. For patients < 50 kg, the dose is 75 mg. For patients ≥ 50 kg, the dose is 150 mg. ( 2.3 ) Psoriatic Arthritis: Adult Patients Subcutaneous Dosage: For PsA patients with coexistent moderate to severe PsO, use the dosage and administration for PsO. ( 2.3 ) For other PsA patients, administer with or without a loading dosage. With a loading dosage : 150 mg at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter Without a loading dosage : 150 mg every 4 weeks If a patient continues to have active PsA, consider a dosage of 300 mg every 4 weeks. ( 2.4 ) Intravenous Dosage: The recommended intravenous dosages are: With a loading dosage : 6 mg/kg given at Week 0 as a loading dose, followed by 1.75 mg/kg every 4 weeks thereafter (max. maintenance dose 300 mg per infusion). Without a loading dosage : 1.75 mg/kg every 4 weeks (max. maintenance dose 300 mg per infusion). ( 2.4 ) Pediatric Patients 2 Years and Older Subcutaneous Dosages : Administer by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter: For patients ≥ 15 kg and < 50 kg the dose is 75 mg. For patients ≥ 50 kg the dose is 150 mg. ( 2.5 ) Ankylosing Spondylitis: Adult Patients Subcutaneous Dosage: Administer with or without a loading dosage. The recommended dosages are: With a loading dosage : 150 mg at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. Without a loading dosage : 150 mg every 4 weeks. If a patient continues to have active ankylosing spondylitis, consider a dosage of 300 mg every 4 weeks. ( 2.6 ) Intravenous Dosage: The recommended intravenous dosages are: With a loading dosage : 6 mg/kg given at Week 0 as a loading dose, followed by 1.75 mg/kg every 4 weeks thereafter (max. maintenance dose 300 mg per infusion). Without a loading dosage : 1.75 mg/kg every 4 weeks (max. maintenance dose 300 mg per infusion). ( 2.6 ) Pediatric Patients 12 Years and Older Subcutaneous Dosage: Administer by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. For patients < 50 kg, the dose is 75 mg. For patients ≥ 50 kg, the dose is 150 mg. ( 2.7 ) Non-Radiographic Axial Spondyloarthritis: Subcutaneous Dosage: Administer with or without a loading dosage. The recommended dosage is: With a loading dosage : 150 mg at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. Without a loading dosage : 150 mg every 4 weeks. ( 2.8 ) Intravenous Dosage: The recommended intravenous dosages are: With a loading dosage : 6 mg/kg given at Week 0 as a loading dose, followed by 1.75 mg/kg every 4 weeks thereafter (max. maintenance dose 300 mg per infusion). Without a loading dosage : 1.75 mg/kg every 4 weeks (max. maintenance dose 300 mg per infusion). ( 2.8 ) Enthesitis-Related Arthritis: Recommended weight-based dosage is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. For patients ≥ 15 kg and < 50 kg the dose is 75 mg. For patients ≥ 50 kg the dose is 150 mg. ( 2.9 ) Hidradenitis Suppurativa: Subcutaneous Dosage in Adults : Recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 and every 4 we…

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 s…

4 CONTRAINDICATIONS COSENTYX is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients in COSENTYX. Cases of anaphylaxis and angioedema have been reported during treatment with COSENTYX [see Warnings and Precautions (5.2)] . Serious hypersensitivity to secukinumab or any excipients in COSENTYX. ( 4 )

7 DRUG INTERACTIONS Certain CYP450 Substrates Increased concentrations of cytokines (e.g., IL-17) during chronic inflammation associated with certain diseases including PsO, PsA, AS, nr-axSpA, ERA, and HS may suppress the formation of CYP enzymes. Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those where minimal decreases in the concentration may reduce CYP substrate effectiveness or minimal increases in the concentration may increase CYP substrate adverse reactions, consider monitoring for therapeutic effect or concentration of the CYP substrate and consider dosage adjustment of the CYP substrate as needed [see Clinical Pharmacology (12.3)] .

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.

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 treat…