COSENTYX

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 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.

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.

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.

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 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.

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.

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. active psoriatic arthritis (PsA) in adults and pediatric patients 2 years of age and older. active ankylosing spondylitis (AS) in adults and pediatric patients 12 years of age and older. active non-radiographic axial spondyloarthritis (nr-axSpA) in adults with objective signs of inflammation. active enthesitis-related arthritis (ERA) in pediatric patients 4 years of age and older. moderate to severe hidradenitis suppurativa (HS) in adults and pediatric patients 12 years of age and older. 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.

Mechanism of Action Secukinumab is a 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 a 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 and in HS lesions.

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 were increased following secukinumab treatment.

These pharmacodynamic activities are based on small exploratory trials.

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.

IL-17A producing lymphocytes have also been found in patients with nr-axSpA.

Immune Response to Non-Live Vaccines During Treatment Healthy individuals who received a single 150 mg dose of COSENTYX 2 weeks prior to vaccination with a non-U.S.-approved group C meningococcal polysaccharide conjugate vaccine and a 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. 12.3 Pharmacokinetics Pharmacokinetics Following Subcutaneous Administration The observed pharmacokinetics (PK) of secukinumab administered subcutaneously in patients with PsO, PsA, AS and nr-axSpA were similar.

The secukinumab PK is also similar in pediatric patients with ERA and PsO for the same weight tiered dosing regimen.

The mean steady-state trough concentration of secukinumab was approximately 26% lower in HS subjects than that of PsO subjects.

Following a single subcutaneous dose of either 150 mg or 300 mg (administered as two injections of 150 mg) of COSENTYX in PsO subjects, secukinumab reached peak mean (± SD) serum concentrations (C max ) of 13.7 ± 4.8 mcg/mL and 27.3 ± 9.5 mcg/mL, respectively, by approximately 6 days post dose.

Following multiple subcutaneous doses of

COSENTYX (administered as one or two injections of 150 mg), 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 approximately 30% higher than those from the prefilled syringe.

Following multiple subcutaneous doses of 300 mg administered via the 300 mg/2 mL UnoReady pen, the mean serum trough concentrations of secukinumab were generally consistent with those in the previous Sensoready pen study used to deliver 300 mg. Steady-state concentrations of secukinumab were achieved by Week 24 following the every 4-week dosing regimen.

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 administered as two injections of 150 mg).

In healthy subjects and subjects with

PsO, secukinumab bioavailability ranged from 55% to 77% following subcutaneous COSENTYX dose of 150 mg or 300 mg (administered as two injections of 150 mg).

Following subcutaneous administrations of 300 mg of COSENTYX at Weeks 0, 1, 2, 3, and and then every 4 weeks thereafter, steady-state concentrations of secukinumab were achieved by Week in both HS trials.

The mean (± SD) steady-state trough concentrations were 25.7 ± 15.7 mcg/mL and 26.0 ± 13.9 mcg/mL in HS Trial and HS Trial 2, respectively.

Following subcutaneous administrations of 300 mg of COSENTYX at Weeks 0, 1, 2, 3, and and then every 2 weeks thereafter, steady-state concentrations of secukinumab were achieved by Week in both HS trials.

The mean (± SD) steady-state trough concentrations were 55.0 ± 26.1 mcg/mL and 58.1 ± 30.1 mcg/mL in HS Trial and HS Trial 2, respectively.

The mean volume of distribution during the terminal phase (Vz) following a single intravenous administration ranged from 7.10 to 8.60 L in PsO subjects.

Secukinumab concentrations in interstitial fluid in lesional and non-lesional skin of PsO subjects ranged from 27% to 40% of those in serum at and 2 weeks after a single subcutaneous dose of COSENTYX 300 mg (administered as two injections of 150 mg).

The metabolic pathway of secukinumab has not been characterized.

As a human

IgG1κ monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

The mean systemic clearance (CL) ranged from 0.14 L/day to 0.22 L/day and the mean half-life ranged from to 31 days in PsO subjects following intravenous and subcutaneous administration across all PsO trials.

In a population

PK analysis, the mean systemic CL in subjects with HS was 0.26 L/day. The mean elimination half-life, as estimated from population PK analysis, was 23 days in HS subjects.

Dose Linearity Secukinumab exhibited dose-proportional

PK in subjects with PsO over a dose range from 25 mg (approximately 0.083 times the recommended dose) to 300 mg following subcutaneous administrations.

Secukinumab clearance and volume of distribution increase as body weight increases.

Specific Populations Patients with Hepatic or Renal Impairment No formal trial of the effect of hepatic or renal impairment on the PK of secukinumab was conducted.

PK analysis indicated that the clearance of secukinumab was not significantly influenced by age in adult subjects with PsO, PsA and AS.

Subjects who are 65 years and older had apparent clearance of secukinumab similar to subjects less than 65 years old.

In a pool of the two pediatric trials, subjects with moderate to severe PsO (6 years of age and older) were administered subcutaneous COSENTYX 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 who weighed less than 25 kg and received 75 mg of subcutaneous COSENTYX, subjects who weighed at least 25 kg and less than 50 kg and received 75 mg of subcutaneous COSENTYX, and subjects who weighed at least 50 kg and received 150 mg of subcutaneous COSENTYX, respectively.

In a pediatric trial, JPsA and ERA patients (2 to less than 18 years of age) were administered subcutaneous COSENTYX at the recommended pediatric dosing regimen.

At Week 24, patients who weighed at least 15 kg and less than 50 kg, and patients who weighed at least 50 kg had a 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.

Based on population pharmacokinetic modeling and simulation, secukinumab concentrations for the every 4-week dosing regimen in pediatric patients 12 years of age and older who weigh at least 30 kg with moderate to severe HS are predicted to be similar to exposures observed in adults with moderate to severe HS who received 300 mg of subcutaneous COSENTYX administered every 4 weeks.

The observed pre-dose (trough) concentrations are generally comparable between adults with AS, PsO, and PsA and pediatric patients with PsO, JPsA, and ERA.

Based on

PK comparison, secukinumab concentrations in pediatric patients (12 years of age and older) with JAS who received the recommended pediatric dosing regimen were predicted to be comparable to exposures observed in adults with AS.

P450 Substrates In adult subjects with PsO, midazolam (CYP3A4 substrate) PK was similar when administered alone, or when administered following either a single or five weekly subcutaneous administrations of 300 mg of COSENTYX.

Pharmacokinetics Following Intravenous Administration

Following an intravenous administration of 1.75 mg/kg maintenance dose every 4 weeks, with or without a loading dose of 6 mg/kg at Day 0, the secukinumab concentrations [steady state trough secukinumab concentrations (C min,ss ), mean secukinumab concentrations (C avg,ss ), and maximum secukinumab concentrations (C max,ss )] are estimated to be within the range of the steady state concentrations following subcutaneous administration of 150 mg and 300 mg doses of COSENTYX administered every 4 weeks. 12.6 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay.

Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies (ADA) in the trials described below with the incidence of ADA in other trials, including those of COSENTYX (secukinumab).

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.

In up to 52 weeks of treatment in controlled trials in adult patients with PsO, PsA, AS, nr-axSpA, HS, and in pediatric patients with PsO, JPsA and ERA, the incidence of anti-secukinumab antibodies (referred as ADA) formation was less than 1% (25 of 6268 total of subjects treated with COSENTYX).

Of the subjects treated with COSENTYX who developed ADA, approximately 8% developed neutralizing antibodies.

Because of the low occurrence of

ADA, the effect of these antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of COSENTYX is unknown.

Infections Hypersensitivity Reactions Inflammatory Bowel Disease Eczematous Eruptions Most common adverse reactions (> 1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection.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 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.

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 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 85 60 Diarrhea 28 18 10 Upper respiratory tract infection 17 22 5 Rhinitis 10 10 5 Oral herpes 9 1 2 Pharyngitis 8 7 0 Urticaria 4 8 1 Rhinorrhea 8 2 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.

COSENTYX groups, subjects with body weight (BW) less than 25 kg received 75 mg, subjects with BW 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 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 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.

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 profil.

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.

Consider contacting the Poison

Help line or a medical toxicologist for additional overdose management recommendations.

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.

Serious hypersensitivity to secukinumab or any excipients in COSENTYX.

Prior to

COSENTYX initiation, complete all age-appropriate vaccinations, evaluate patients for tuberculosis (TB).

Information for instructions on preparation and administration of COSENTYX.

COSENTYX for intravenous use must be diluted prior to administration.

Administer as an intravenous infusion after dilution over a period of 30 minutes.

Subcutaneous Dosage in Adults: Recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

For some patients, a dose of 150 mg may be acceptable.

Patients 6 Years and Older: Recommended weight-based dosage is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

For patients < 50 kg, the dose is 75 mg. For patients ≥ 50 kg, the dose is 150 mg. Psoriatic Arthritis: Adult Patients Subcutaneous Dosage: For PsA patients with coexistent moderate to severe PsO, use the dosage and administration for PsO.

For other

PsA patients, administer with or without a loading dosage.

With a loading dosage: 150 mg at Weeks 0, 1, 2, 3, and 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.

The recommended intravenous dosages are: With a loading dosage: 6 mg/kg given at Week 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).

Patients 2 Years and Older Subcutaneous Dosages: Administer by subcutaneous injection at Weeks 0, 1, 2, 3, and 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. 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 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.

Patients 12 Years and Older Subcutaneous Dosage: Administer by subcutaneous injection at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

For patients < 50 kg, the dose is 75 mg. For patients ≥ 50 kg, the dose is 150 mg. Non-Radiographic Axial Spondyloarthritis: Subcutaneous Dosage: Administer with or without a loading dosage.

The recommended dosage is

Recommended weight-based dosage is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and 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. Hidradenitis Suppurativa: Subcutaneous Dosage in Adults: Recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

If a patient does not adequately respond, consider increasing the dosage to 300 mg every 2 weeks.

Patients 12 Years and Older: Recommended weight-based dosage is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

For patients ≥ 30 kg and < 90 kg, the dose is 150 mg. For patients ≥ 90 kg, the dose is 300 mg. 2.1 Testing and Procedures Prior to Treatment Initiation Perform the following evaluations prior to COSENTYX initiation: Evaluate for active or latent tuberculosis (TB).

COSENTYX initiation is not recommended in patients with active TB infection.

Initiate treatment of latent TB prior to initiation of COSENTYX.

Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with COSENTYX. 2.2 Important Administration Instructions COSENTYX is for use under the guidance and supervision of a healthcare provider.

UnoReady pen, Sensoready pen, and prefilled syringes are for subcutaneous use only.

Solution in vials is for intravenous use in adult patients only.

Important Subcutaneous Administration Instructions

Adult patients may self-administer COSENTYX or be injected by a caregiver after proper training in subcutaneous injection technique.

Pediatric patients should not self-administer

An adult caregiver should prepare and inject COSENTYX after proper training in subcutaneous injection technique.

Administer each subcutaneous injection at a 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 subcutaneous

COSENTYX in the upper, outer arm may be performed by a caregiver or healthcare provider.

COSENTYX “Instructions for Use” for each presentation and strength contains more detailed instructions on the preparation and administration of COSENTYX for patients and caregivers.

Intravenous infusion is only for use by a healthcare professional in a healthcare setting.

Prepare COSENTYX intravenous infusion by diluting

COSENTYX injection in vial(s) and administering based on patient body weight.

Intravenous infusion may be administered only in adults with PsA, AS, and nr-axSpA. 2.3 Recommended Dosage in Plaque Psoriasis Recommended Subcutaneous Dosage in Adults The recommended dosage in adults with PsO is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

Each 300 mg dosage is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg. For some patients, a dosage of 150 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter may be acceptable.

Patients 6 Years of Age and Older The recommended weight-based dosage in pediatric patients 6 years of age and older with PsO is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

For patients < 50 kg, the recommended dose is 75 mg. For patients ≥ 50 kg, the recommended dose is 150 mg. 2.4 Recommended Dosage in Adults with Psoriatic Arthritis COSENTYX may be administered with or without methotrexate.

Recommended Subcutaneous Dosage For adult patients with PsA and with coexistent moderate to severe PsO, use the dosage and administration recommendations for adults with PsO.

For other adult patients with

PsA, administer COSENTYX with or without a loading dosage by subcutaneous injection.

The recommended dosage in adults with PsA: With a loading dosage is 150 mg at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

Without a loading dosage is 150 mg every 4 weeks.

If a patient continues to have active PsA, consider increasing the dosage to 300 mg by subcutaneous injection every 4 weeks.

Each 300 mg dosage is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg. Recommended Intravenous Dosage COSENTYX injection for intravenous use (solution in vials) requires dilution prior to intravenous administration.

The recommended intravenous dosage regimen in adults with PsA: With a loading dosage is 6 mg/kg loading dose given at Week 0, followed by 1.75 mg/kg every 4 weeks thereafter (maintenance dosage).

Without a loading dosage is 1.75 mg/kg every 4 weeks.

Administer as an intravenous infusion over a period of 30 minutes.

Total doses exceeding 300 mg per infusion are not recommended for the 1.75 mg/kg maintenance dose in adults with PsA. 2.5 Recommended Dosage in Pediatric Patients 2 Years of Age and Older with Juvenile Psoriatic Arthritis COSENTYX may be administered with or without methotrexate.

The recommended weight-based subcutaneous dosage in pediatric patients 2 years of age and older with PsA at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter is as follows: For patients ≥ 15 kg and < 50 kg, the recommended dose is 75 mg. For patients ≥ 50 kg, the recommended dose is 150 mg. 2.6 Recommended Dosage in Adults with Ankylosing Spondylitis Recommended Subcutaneous Dosage Administer COSENTYX with or without a loading dosage by subcutaneous injection in adult patients with active AS.

The recommended dosage

With a loading dosage is 150 mg at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter.

If a patient continues to have active AS, consider increasing the dosage to 300 mg every 4 weeks by subcutaneous injection.

The recommended intravenous dosage regimen in adult patients with active AS: With a loading dosage is 6 mg/kg loading dose given at Week 0, followed by 1.75 mg/kg every 4 weeks thereafter (maintenance dosage).

Total doses exceeding 300 mg per infusion are not recommended for the 1.75 mg/kg maintenance dose in patients with AS. 2.7 Recommended Dosage in Pediatric Patients 12 Years of Age and Older with Juvenile Ankylosing Spondylitis The recommended weight-based subcutaneous dosage in pediatric patients 12 years of age and older with AS at Weeks 0, 1, 2, 3, and and every 4 weeks thereafter is as follows: For patients < 50 kg, the recommended dose is 75 mg. For patients ≥ 50 kg, the recommended dose is 150 mg. 2.8 Recommended Dosage in Adults with Non-Radiographic Axial Spondyloarthritis Recommended Subcutaneous Dosage Administer COSENTYX with or without a loading dosage by subcutaneous injection in adult patients with active nr-axSpA.

COSENTYX injection for intravenous use (solution in vials) requires dilution prior to intravenous administration.

The recommended intravenous dosage regimen in adult patients with active nr-axSpA: With a loading dosage is 6 mg/kg loading dose given at Week 0, followed by 1.75 mg/kg every 4 weeks thereafter (maintenance dosage).

Total doses exceeding 30.

COSENTYX (secukinumab) injection is a clear to opalescent, colorless to slightly yellowish solution available as follows: COSENTYX injection for subcutaneous use Strength Dosage Form Carton Contents NDC 75 mg/0.5 mL COSENTYX prefilled syringe 1 prefilled syringe 0078-1056-97 150 mg/mL COSENTYX prefilled syringe 1 prefilled syringe 0078-0639-97 2 prefilled syringes 0078-0639-98 COSENTYX Sensoready pen 1 Sensoready pen 0078-0639-68 2 Sensoready pens 0078-0639-41 300 mg/2 mL COSENTYX prefilled syringe 1 prefilled syringe 0078-1070-97 COSENTYX UnoReady pen 1 UnoReady pen 0078-1070-68 The removable cap of the COSENTYX Sensoready pen and prefilled syringes (150 mg/mL, 75 mg/0.5 mL) contains natural rubber latex.

COSENTYX pens and prefilled syringes are equipped with a needle safety guard.

COSENTYX injection for intravenous use Strength Dosage Form Carton Contents NDC 125 mg/5 mL COSENTYX vial 1 vial of solution for dilution prior to intravenous infusion 0078-1168-61 Storage and Handling Refrigerate COSENTYX at 2ºC to 8ºC (36ºF to 46ºF).

COSENTYX 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 a preservative; discard any unused portion.

If removed from refrigeration, COSENTYX Sensoready pen and prefilled syringes (150 mg/mL, 75 mg/0.5 mL): May be stored for up to 4 days at room temperature not to exceed 30°C (86°F).

Write the date

COSENTYX is removed from and returned to the refrigerator in the space provided on the carton.

Discard if stored outside of the refrigerator over 4 days.

May be returned to the refrigerator only one time and must be stored at 2ºC to 8ºC (36ºF to 46ºF) until used or expired.

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) .

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.

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 and on postpartum days 4, 10, and at doses up to 150 mg/kg/dose.

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.

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.

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.

The safety and effectiveness of COSENTYX in pediatric patients with JAS below the age of 12 years old have not been established.

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.

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.

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.

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) .

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.

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.