TALTZ

Warnings and Precautions ( 5.1 , 5.4 ) 08/2024

1 INDICATIONS AND USAGE TALTZ ® is a humanized interleukin-17A antagonist indicated for the treatment of: patients aged 6 years or older with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. ( 1.1 ) adults with active psoriatic arthritis. ( 1.2 ) adults with active ankylosing spondylitis. ( 1.3 ) adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation. ( 1.4 ) 1.1 Plaque Psoriasis TALTZ ® is indicated for the treatment of patients 6 years of age and older with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. 1.2 Psoriatic Arthritis TALTZ is indicated for the treatment of adult patients with active psoriatic arthritis. 1.3 Ankylosing Spondylitis TALTZ is indicated for the treatment of adult patients with active ankylosing spondylitis. 1.4 Non-radiographic Axial Spondyloarthritis TALTZ is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.

2 DOSAGE AND ADMINISTRATION Administer by subcutaneous injection. Adult Plaque Psoriasis ( 2.2 ) Recommended dosage is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks. Pediatric Plaque Psoriasis ( 2.3 ) For patients weighing greater than 50 kg, recommended dosage is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks. For patients weighing 25-50 kg, recommended dosage is 80 mg at Week 0, followed by 40 mg every 4 weeks. For patients weighing less than 25 kg, recommended dosage is 40 mg at Week 0, followed by 20 mg every 4 weeks. Psoriatic Arthritis ( 2.4 ) Recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks. For psoriatic arthritis patients with coexistent moderate-to-severe plaque psoriasis, use the dosing regimen for adult plaque psoriasis. ( 2.2 ) TALTZ may be administered alone or in combination with a conventional DMARD (e.g., methotrexate). Ankylosing Spondylitis ( 2.5 ) Recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks. Non-radiographic Axial Spondyloarthritis ( 2.6 ) Recommended dosage is 80 mg by subcutaneous injection every 4 weeks. 2.1 Testing and Procedures Prior to Treatment Initiation Perform the following evaluations prior to TALTZ initiation: Evaluate patients for tuberculosis (TB) infection. TALTZ initiation is not recommended in patients with active TB infection. Initiate treatment of latent TB prior to initiation of TALTZ [see Warnings and Precautions ( 5.2 )] . Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with TALTZ [see Warnings and Precautions ( 5.6 )] . 2.2 Recommended Dosage in Adult Plaque Psoriasis TALTZ is administered by subcutaneous injection. The recommended dosage in adults with moderate-to-severe plaque psoriasis is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks. 2.3 Recommended Dosage in Pediatric Plaque Psoriasis TALTZ is administered by subcutaneous injection every 4 weeks (Q4W). The recommended dosage in pediatric patients from 6 to less than 18 years of age with moderate-to-severe plaque psoriasis is based on the following weight categories. Table 1: Recommended Dosage for Pediatric Patients 6 Years of Age and Older with Plaque Psoriasis Pediatric Patient's Weight Starting Dose (Week 0) Dose every 4 weeks (Q4W) Thereafter Greater than 50 kg 160 mg (two 80 mg injections) 80 mg 25 to 50 kg 80 mg 40 mg Less than 25 kg 40 mg 20 mg 2.4 Recommended Dosage in Psoriatic Arthritis The recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks. For psoriatic arthritis patients with coexistent moderate-to-severe plaque psoriasis, use the dosing regimen for adult plaque psoriasis [see Dosage and Administration ( 2.2 )] . TALTZ may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate). 2.5 Recommended Dosage in Ankylosing Spondylitis The recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks. 2.6 Recommended Dosage in Non-radiographic Axial Spondyloarthritis The recommended dosage is 80 mg by subcutaneous injection every 4 weeks. 2.7 Preparation and Administration Instructions TALTZ is intended for use under the guidance and supervision of a healthcare provider. Adult patients may self-inject or caregivers may give injections of TALTZ after training in subcutaneous injection technique using the autoinjector or prefilled syringe. Safety and effectiveness of pediatric self-administration has not been established. Therefore, TALTZ should be administered to pediatric patients by a healthcare provider or by a caregiver who has received train …

3 DOSAGE FORMS AND STRENGTHS TALTZ is a clear and colorless to slightly yellow solution available as: Injection: 80 mg/mL solution of TALTZ in a single-dose prefilled autoinjector Injection: 80 mg/mL solution of TALTZ in a single-dose prefilled syringe Injection: 40 mg/0.5 mL solution of TALTZ in a single-dose prefilled syringe Injection: 20 mg/0.25 mL solution of TALTZ in a single-dose prefilled syringe Injection: ( 3 ) 80 mg/mL solution in a single-dose prefilled autoinjector 80 mg/mL solution in a single-dose prefilled syringe 40 mg/0.5 mL solution in a single-dose prefilled syringe 20 mg/0.25 mL solution in a single-dose prefilled syringe

4 CONTRAINDICATIONS TALTZ is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients [see Warnings and Precautions ( 5.3 )] . Serious hypersensitivity reaction to ixekizumab or to any of the excipients. ( 4 )

6 ADVERSE REACTIONS The following adverse drug reactions are discussed in greater detail in other sections of the label: Infections [see Warnings and Precautions ( 5.1 )] Hypersensitivity Reactions [see Contraindications ( 4 ) and Warnings and Precautions ( 5.3 )] Eczematous Eruptions [see Warnings and Precautions ( 5.4 )] Inflammatory Bowel Disease [see Warnings and Precautions ( 5.5 )] Most common (≥1%) adverse reactions associated with TALTZ treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-545-5979 (1-800-LillyRx) 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 and controlled 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. Adult Plaque Psoriasis Weeks 0 to 12 : Three placebo-controlled trials in subjects with plaque psoriasis were integrated to evaluate the safety of TALTZ compared to placebo for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with plaque psoriasis received TALTZ (160 mg at Week 0, 80 mg every 2 weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of TALTZ (use up to 12 weeks) was also compared with an active comparator, U.S. approved etanercept [see Clinical Studies ( 14 )] . In the 12-week, placebo-controlled period, adverse events occurred in 58% of the TALTZ Q2W group (2.5 per subject-year of follow-up) compared with 47% of the placebo group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the TALTZ group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up). Table 2 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TALTZ group than in the placebo group during the 12-week placebo-controlled period of the pooled clinical trials. Table 2: Adverse Reactions Occurring in ≥1% of the TALTZ Group and More Frequently than in the Placebo Group in the Plaque Psoriasis Clinical Trials through Week 12 a Upper respiratory tract infections cluster includes nasopharyngitis and rhinovirus infection. b U.S. approved etanercept. Adverse Reactions TALTZ 80 mg Q2W (N=1167) n (%) Etanercept b (N=287) n (%) Placebo (N=791) n (%) Injection site reactions 196 (17) 32 (11) 26 (3) Upper respiratory tract infections a 163 (14) 23 (8) 101 (13) Nausea 23 (2) 1 (<1) 5 (1) Tinea infections 17 (2) 0 1 (<1) Adverse reactions that occurred at rates less than 1% in the TALTZ group and more frequently than in the placebo group during the 12-week induction period included rhinitis, oral candidiasis, urticaria, influenza, conjunctivitis, inflammatory bowel disease, and angioedema. Weeks 13 to 60 : A total of 332 subjects received the recommended maintenance regimen of TALTZ 80 mg dosed every 4 weeks. During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with TALTZ (1.0 per subject-year of follow-up) compared to 58% of subjects treated with placebo (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with TALTZ (0.05 per subject-year of follow-up) and none in the subjects treated with placebo. Weeks 0 to 60 : Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with TALTZ (1.4 per subject-year of follow-up) compared to 48% of subjects treated with placebo (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with TALTZ (0.06 per subject-year of follow-up), and in 2% of subjects treated with placebo (0.06 per subject-year of follow-up). Specific Adverse Drug Reactions Injection Site React …

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TALTZ during pregnancy. Pregnant women exposed to TALTZ are encouraged to enroll in the TALTZ Pregnancy Registry by calling 1-800-284-1695. Contact information for the registry is also available on http://www.pregnancyregistry.lilly.com. Risk Summary Available data from the published literature and the pharmacovigilance database with TALTZ use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Human IgG is known to cross the placental barrier; therefore, TALTZ may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys during organogenesis at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD [see Data] . The clinical significance of these nonclinical findings is unknown. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by subcutaneous injection during organogenesis to near parturition at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys. In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly subcutaneous doses of ixekizumab up to 19 times the MRHD from the beginning of organogenesis to parturition. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or congenital defect. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the surviving infants from birth through 6 months of age. 8.2 Lactation Risk Summary There are no available data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TALTZ and any potential adverse effects on the breastfed infant from TALTZ or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of TALTZ have been established in pediatric subjects aged 6 years to less than 18 years with moderate-to-severe plaque psoriasis. The safety and effectiveness of TALTZ in other pediatric indications and for pediatric subjects less than 6 years of age have not been established. 8.5 Geriatric Use Of the 4204 adult psoriasis subjects exposed to TALTZ, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects [see Clinical Pharmacology ( 12. …

12.1 Mechanism of Action Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds with 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. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.

11 DESCRIPTION Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) with neutralizing activity against IL-17A. Ixekizumab is produced by recombinant DNA technology in a recombinant mammalian cell line and purified using standard technology for bioprocessing. Ixekizumab is comprised of two identical light chain polypeptides of 219 amino acids each and two identical heavy chain polypeptides of 445 amino acids each and has a molecular weight of 146,158 Daltons for the protein backbone of the molecule. TALTZ injection is a sterile, preservative free, clear and colorless to slightly yellow solution, for subcutaneous use available as 80 mg of ixekizumab in a 1 mL single-dose prefilled autoinjector or a single-dose prefilled syringe, 40 mg of ixekizumab in a 0.5 mL single-dose prefilled syringe, or 20 mg of ixekizumab in a 0.25 mL single-dose prefilled syringe. The prefilled autoinjector and prefilled syringe each contain a 1 mL glass syringe with a fixed 27 gauge 1⁄2 inch needle. The TALTZ 80 mg prefilled autoinjector and prefilled syringe are manufactured to deliver 80 mg of ixekizumab. The TALTZ 40 mg prefilled syringe is manufactured to deliver 40 mg of ixekizumab. The TALTZ 20 mg prefilled syringe is manufactured to deliver 20 mg of ixekizumab. Each TALTZ 80 mg/mL single-dose autoinjector or TALTZ 80 mg/mL single-dose prefilled syringe is composed of ixekizumab (80 mg); Polysorbate 80, USP (0.3 mg); Sucrose, USP (80 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 – 6.2. Each TALTZ 40 mg/0.5 mL single-dose prefilled syringe is composed of ixekizumab (40 mg); Polysorbate 80, USP (0.15 mg); Sucrose, USP (40 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 – 6.2. Each TALTZ 20 mg/0.25 mL single-dose prefilled syringe is composed of ixekizumab (20 mg); Polysorbate 80, USP (0.08 mg); Sucrose, USP (20 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 – 6.2.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied TALTZ injection is a sterile, preservative free, clear and colorless to slightly yellow solution available in: a single-dose prefilled autoinjector or a single-dose prefilled syringe to deliver 80 mg ixekizumab. a single-dose prefilled syringe to deliver 40 mg ixekizumab. a single-dose prefilled syringe to deliver 20 mg ixekizumab. TALTZ is supplied as: Pack Size NDC Code Autoinjector Carton of 1 0002-1445-11 80 mg single-dose Carton of 2 0002-1445-27 Carton of 3 0002-1445-09 Prefilled syringe 80 mg single-dose Carton of 1 0002-7724-11 40 mg single-dose Carton of 1 0002-8905-11 20 mg single-dose Carton of 1 0002-8900-11 Storage and Handling TALTZ is sterile and preservative-free. Discard any unused portion. TALTZ must be protected from light until use. Store refrigerated at 2°C to 8°C (36°F to 46°F). If needed, patients/caregivers may store TALTZ at room temperature up to 30°C (86°F) for up to 5 days in the original carton to protect from light. Once TALTZ has been stored at room temperature, do not return to the refrigerator and discard, if unused, within 5 days. Record the date when TALTZ is first removed from the refrigerator in the spaces provided on the carton. For the 2 or 3 autoinjector pack, remove a single autoinjector at a time leaving the remaining autoinjector(s) in the original carton in the refrigerator. Ensure the unrefrigerated TALTZ is protected from light. Do not freeze. Do not use TALTZ if it has been frozen. Do not shake. Discard the TALTZ single-dose autoinjector or syringe after use in a puncture-resistant container. Not made with natural rubber latex.

How Supplied TALTZ injection is a sterile, preservative free, clear and colorless to slightly yellow solution available in: a single-dose prefilled autoinjector or a single-dose prefilled syringe to deliver 80 mg ixekizumab. a single-dose prefilled syringe to deliver 40 mg ixekizumab. a single-dose prefilled syringe to deliver 20 mg ixekizumab. TALTZ is supplied as: Pack Size NDC Code Autoinjector Carton of 1 0002-1445-11 80 mg single-dose Carton of 2 0002-1445-27 Carton of 3 0002-1445-09 Prefilled syringe 80 mg single-dose Carton of 1 0002-7724-11 40 mg single-dose Carton of 1 0002-8905-11 20 mg single-dose Carton of 1 0002-8900-11