Cosentyx Drug Information

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.

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

Important Intravenous Infusion Instructions 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.

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 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 and every 4 weeks thereafter may be acceptable.

Recommended Subcutaneous Dosage in Pediatric 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 and every 4 weeks thereafter. For patients < 50 kg, the recommended dose is 75 mg.

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 and every 4 weeks thereafter. If a patient continues to have active PsA, consider increasing the dosage to 300 mg by subcutaneous injection every 4 weeks. Recommended Intravenous Dosage COSENTYX injection for intravenous use (solution in vials) requires dilution prior to intravenous administration.

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.

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.

Recommended Dosage in Enthesitis-Related Arthritis COSENTYX may only be administered as a subcutaneous injection in pediatric patients aged 4 years and older with active ERA.

Recommended Dosage in Hidradenitis Suppurativa Recommended Subcutaneous Dosage in Adults The recommended dosage in adult patients with moderate to severe HS is 300 mg by subcutaneous injection at Weeks and every 4 weeks thereafter. If an adult patient does not adequately respond, consider increasing the dosage to 300 mg every 2 weeks. For patients ≥ 30 kg and < 90 kg, the recommended dose is 150 mg.

The removable cap of the COSENTYX Sensoready pen and prefilled syringes (150 mg/mL, 75 mg/0.5 mL) contains natural rubber latex and should not be handled by latex-sensitive individuals. Inspect COSENTYX visually for particulate matter and discoloration prior to administration. COSENTYX injection is a clear to slightly opalescent, colorless to slightly yellow solution.

Do not use if the liquid contains visible particles, is discolored or cloudy. Discard any unused product.

Preparation and Administration of COSENTYX for Intravenous Use COSENTYX (for intravenous use) must be diluted prior to infusion. Using aseptic technique, prepare COSENTYX (for intravenous use) as follows: Step 1. Volume Calculation Calculate the total volume of COSENTYX for intravenous use solution (in mL) required based on the patient’s actual body weight as follows: Loading dose (6 mg/kg) is 0.24 mL/kg Maintenance dose (1.75 mg/kg) is 0.07 mL/kg Use the number of vials based on total volume needed (one vial contains 5 mL of COSENTYX solution).

Step 2. Dilution Parenteral drug product should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulates or discolorations are noted.

Follow Table 1 for recommended infusion bag size based on patient's body weight. Table 1: Recommended Infusion Bags for Dilution and Preparation of COSENTYX for Intravenous Use Based on Body Weight and Dose From the infusion bag, withdraw and discard a volume of 0.9% Sodium Chloride Injection, USP, equal to the calculated volume of the COSENTYX solution required for the patient’s dose. From the vial(s), withdraw the calculated volume (mL) of COSENTYX solution and add slowly into the 0.9% Sodium Chloride Injection, USP infusion bag.

To mix the solution, gently invert the bag to avoid foaming. Do not shake. Discard unused COSENTYX product in vials because it does not contain preservatives.

Allow the diluted COSENTYX solution for infusion to warm to room temperature prior to the start of the intravenous infusion. Administer the diluted COSENTYX solution for infusion as soon as possible. If not administered immediately, store the diluted solution either: At room temperature 20ºC to 25ºC (68ºF to 77ºF) for no more than 4.5 hours from the start of the preparation (piercing the first vial) to the completion of infusion.

Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours, from the start of the time of the preparation (piercing the first vial) to the completion of infusion. This time includes the refrigeration of the diluted solution and the time to allow the diluted solution to warm to room temperature. Protect the diluted solution from light during storage under refrigeration.

Step 3. Administration Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.2 micrometer). When administration is complete, flush the line with 0.9% Sodium Chloride Injection, USP to guarantee that all the COSENTYX solution for infusion in the line has been administered.

Do not infuse COSENTYX concomitantly in the same intravenous line with other drugs. No physical or biochemical compatibility studies have been conducted to evaluate the IV coadministration of COSENTYX with other drugs.

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. Subjects randomized to COSENTYX received 300 mg or 150 mg doses subcutaneously at Weeks 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 12 in Trials PsO1, PsO2, PsO3, and PsO4 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. 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.

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. 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 ) who were candidates for systemic therapy.

The 162 subjects were randomized to receive placebo, a biologic active control, or COSENTYX. Subjects were dosed at Weeks 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.

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. 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 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.

In the original AS program, with 571 patients exposed to COSENTYX, there were 8 cases of IBD during the entire treatment period. 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. 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. 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.

The safety profile of COSENTYX observed in these HS trials was consistent with the known safety profile of COSENTYX observed in the PsO trials. 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.

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

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.

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.

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. 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.

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. 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. 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. 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.

Intravenous Administration The safety and effectiveness of intravenous COSENTYX in pediatric patients have not been established.

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.

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 (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.