Tildrakizumab Asmn

5 WARNINGS AND PRECAUTIONS Hypersensitivity: If a serious allergic reaction occurs, discontinue ILUMYA immediately and initiate appropriate therapy. ( 5.1 ) Infections : ILUMYA may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, consider discontinuing ILUMYA until the infection resolves. ( 5.2 ) Pretreatment Evaluation for Tuberculosis (TB): Evaluate for TB prior to initiating treatment. ( 5.3 ) Immunizations : Avoid use of live vaccines. ( 5.4 ) 5.1 Hypersensitivity Cases of angioedema and urticaria occurred in ILUMYA treated subjects in clinical trials. If a serious hypersensitivity reaction occurs, discontinue ILUMYA immediately and initiate appropriate therapy [see Adverse Reactions (6.1) ]. 5.2 Infections ILUMYA may increase the risk of infection. Although infections were more common in the ILUMYA group (23%), the difference in frequency of infections between the ILUMYA group and the placebo group (22%) was less than 1% during the placebo-controlled period. However, subjects with active infections or a history of recurrent infections were not included in clinical trials. Upper respiratory infections occurred more frequently in the ILUMYA group than in the placebo group [see Adverse Reactions (6.1) ] . The rates of serious infections for the ILUMYA group and the placebo group were ≤0.3%. Treatment with ILUMYA should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing ILUMYA. Instruct patients to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, monitor the patient closely and consider discontinuation of ILUMYA until the infection resolves [see Adverse Reactions (6.1) ] . 5.3 Pretreatment Evaluation for Tuberculosis Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with ILUMYA. Initiate treatment of latent TB prior to administering ILUMYA. In clinical trials, of 55 subjects with latent TB who were concurrently treated with ILUMYA and appropriate TB prophylaxis, no subjects developed active TB (during the mean follow-up of 56.5 weeks). One other subject developed TB while receiving ILUMYA. Monitor patients for signs and symptoms of active TB during and after ILUMYA treatment. Consider anti-TB therapy prior to initiation of ILUMYA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Do not administer ILUMYA to patients with active TB infection. 5.4 Immunizations Prior to initiating therapy with ILUMYA, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid the use of live vaccines in patients treated with ILUMYA. No data are available on the response to live or inactive vaccines.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Most common (≥1%) adverse reactions associated with ILUMYA treatment are upper respiratory infections, injection site reactions, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 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. Plaque Psoriasis In clinical trials, a total of 1994 subjects with plaque psoriasis were treated with ILUMYA, of which 1083 subjects were treated with ILUMYA 100 mg. Of these, 672 subjects were exposed for at least 12 months, 587 for 18 months, and 469 for 24 months. Data from three placebo-controlled trials (Trials 1, 2, and 3) in 705 subjects (mean age 46 years, 71% males, 81% white) were pooled to evaluate the safety of ILUMYA (100 mg administered subcutaneously at Weeks 0 and 4, followed by every 12 weeks [Q12W]) [see Clinical Studies (14) ] . Placebo-Controlled Period (Weeks 0-16 of Trial 1 and Weeks 0-12 of Trials 2 and 3) Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the ILUMYA group than in the placebo group. Table 1: Adverse Reactions Occurring in ≥1% of Subjects in the ILUMYA Group and More Frequently than in the Placebo Group in the Plaque Psoriasis Trials 1, 2, and 3 * Upper respiratory infections include nasopharyngitis, upper respiratory tract infection, viral upper respiratory tract infection, and pharyngitis. † Injection site reactions include injection site urticaria, pruritus, pain, reaction, erythema, inflammation, edema, swelling, bruising, hematoma, and hemorrhage. Adverse Reaction ILUMYA Placebo 100 mg (N=705) (N=355) N (%) N (%) Upper respiratory infections* 98 (14) 41 (12) Injection site reactions † 24 (3) 7 (2) Diarrhea 13 (2) 5 (1) During the placebo-controlled period of Trials 1, 2, and 3, adverse reactions that occurred at rates less than 1% but greater than 0.1% in the ILUMYA group and at a higher rate than in the placebo group included dizziness and pain in extremity. Cases of angioedema and urticaria were reported in ILUMYA-treated subjects in clinical trials . Safety through Week 260 The safety profile of ILUMYA through Week 260 of the open-label extension periods of Trial 2 and Trial 3 was consistent with the safety profile observed during the double-blind periods . Psoriasis of the Scalp The safety of ILUMYA was assessed in a multicenter, randomized, double-blind, placebo-controlled trial (Trial 4) in 231 subjects with psoriasis of the scalp [ see Clinical Studies (14) ]. No new safety signals were identified through follow-up to Week 72. Psoriasis of the Nail The safety of ILUMYA was assessed in a multicenter, randomized, double-blind, placebo-controlled trial (Trial 5) in 99 subjects with psoriasis of the nail [ see Clinical Studies (14) ]. No new safety signals were identified through Week 28.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors outcomes in women with plaque psoriasis who become pregnant while being treated with ILUMYA during pregnancy. These patients can enroll in this registry by calling MotherToBaby a service of the Organization of Teratology Information Specialists (OTIS) at 1-866-626-6847 or by visiting the website https://mothertobaby.org/ongoing-study/ilumya-tildrakizumab-asmn. Risk Summary Available data from clinical trials, published literature, and pharmacovigilance with ILUMYA use in pregnant women are insufficient to inform a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Monoclonal antibodies are actively transported across the placenta (see Clinical Considerations). An embryofetal developmental study conducted with tildrakizumab in pregnant monkeys revealed no treatment-related effects to the developing fetus when tildrakizumab was administered subcutaneously during organogenesis to near parturition at doses up to 159 times the maximum recommended human dose (MRHD). When dosing was continued until parturition, an increase in neonatal death was observed at 59 times the MRHD (see Data). The clinical significance of this nonclinical finding is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Therefore, ILUMYA may be present in infants exposed in utero . The potential clinical impact of tildrakizumab exposure in infants exposed in utero should be considered. Data Animal Data In an embryofetal developmental study, subcutaneous doses up to 300 mg/kg tildrakizumab were administered to pregnant cynomolgus monkeys once every two weeks during organogenesis to gestation day 118 (22 days from parturition). No maternal or embryofetal toxicities were observed at doses up to 300 mg/kg (159 times the MRHD of 100 mg, based on AUC comparison). Tildrakizumab crossed the placenta in monkeys. In a pre- and postnatal developmental study, subcutaneous doses up to 100 mg/kg tildrakizumab were administered to pregnant cynomolgus monkeys once every two weeks from gestation day 50 to parturition. Neonatal deaths occurred in the offspring of one control monkey, two monkeys at 10 mg/kg dose (6 times the MRHD based on AUC comparison), and four monkeys at 100 mg/kg dose (59 times the MRHD based on AUC comparison). The clinical significance of these nonclinical findings is unknown. No tildrakizumab-related adverse effects were noted in the remaining infants from birth through 6 months of age. 8.2 Lactation Risk Summary There are no data on the presence of tildrakizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk. Tildrakizumab was detected in the milk of monkeys [ see Data ] . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ILUMYA and any potential adverse effects on the breastfed child from ILUMYA or from the underlying maternal condition. Data Animal Data Tildrakizumab was detected in breast milk of monkeys in the pre- and postnatal developmental study described in 8.1. The mean tildrakizumab concentrations in milk were approximately 0.09 – 0.2% of that in serum on postpartum days 28 and 91. 8.4 Pediatric Use Safety and effectiveness of ILUMYA in pediatric patients (<18 years of age) have not been established. 8.5 Geriatric Use A total of 1083 subjects were exposed to ILUMYA 100 mg during Phase 2 and 3 trials. A total of 92 subjects were 65 years or older, and 17 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 responded differently from younger subjects [see Clinical Pharmacology (12.3) ] .

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors outcomes in women with plaque psoriasis who become pregnant while being treated with ILUMYA during pregnancy. These patients can enroll in this registry by calling MotherToBaby a service of the Organization of Teratology Information Specialists (OTIS) at 1-866-626-6847 or by visiting the website https://mothertobaby.org/ongoing-study/ilumya-tildrakizumab-asmn. Risk Summary Available data from clinical trials, published literature, and pharmacovigilance with ILUMYA use in pregnant women are insufficient to inform a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Monoclonal antibodies are actively transported across the placenta (see Clinical Considerations). An embryofetal developmental study conducted with tildrakizumab in pregnant monkeys revealed no treatment-related effects to the developing fetus when tildrakizumab was administered subcutaneously during organogenesis to near parturition at doses up to 159 times the maximum recommended human dose (MRHD). When dosing was continued until parturition, an increase in neonatal death was observed at 59 times the MRHD (see Data). The clinical significance of this nonclinical finding is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Therefore, ILUMYA may be present in infants exposed in utero . The potential clinical impact of tildrakizumab exposure in infants exposed in utero should be considered. Data Animal Data In an embryofetal developmental study, subcutaneous doses up to 300 mg/kg tildrakizumab were administered to pregnant cynomolgus monkeys once every two weeks during organogenesis to gestation day 118 (22 days from parturition). No maternal or embryofetal toxicities were observed at doses up to 300 mg/kg (159 times the MRHD of 100 mg, based on AUC comparison). Tildrakizumab crossed the placenta in monkeys. In a pre- and postnatal developmental study, subcutaneous doses up to 100 mg/kg tildrakizumab were administered to pregnant cynomolgus monkeys once every two weeks from gestation day 50 to parturition. Neonatal deaths occurred in the offspring of one control monkey, two monkeys at 10 mg/kg dose (6 times the MRHD based on AUC comparison), and four monkeys at 100 mg/kg dose (59 times the MRHD based on AUC comparison). The clinical significance of these nonclinical findings is unknown. No tildrakizumab-related adverse effects were noted in the remaining infants from birth through 6 months of age.