ICOTYDE

5 WARNINGS AND PRECAUTIONS Infections : Avoid treatment with ICOTYDE in patients with any clinically important active infection until the infection resolves or is adequately treated. If such an infection develops, discontinue ICOTYDE until the infection resolves. ( 5.1 ) Tuberculosis (TB) : Consider evaluating for TB prior to initiating treatment with ICOTYDE based on clinical judgment. Monitor patients for signs and symptoms of active TB during and after treatment with ICOTYDE. ( 5.2 ) Immunizations : Avoid use of live vaccines during treatment with ICOTYDE. ( 5.3 ) 5.1 Infections Medicines that interact with the immune system may increase the risk of infection. In the 16-week placebo-controlled trials in subjects with moderate-to-severe plaque psoriasis, the rate of serious infections for ICOTYDE-treated subjects was 0.2% compared to 0.4% of subjects who received placebo. Avoid treatment with ICOTYDE 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 ICOTYDE. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If a patient develops such an infection and/or is not responding to standard therapy, monitor the patient closely and discontinue ICOTYDE until the infection resolves. 5.2 Tuberculosis Consider evaluating patients for tuberculosis (TB) infection prior to initiating treatment with ICOTYDE based on clinical judgment. Consider anti-TB therapy prior to initiating ICOTYDE in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after ICOTYDE treatment. Avoid administering ICOTYDE to patients with active TB. 5.3 Immunizations Avoid use of live vaccines in patients during treatment with ICOTYDE. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with ICOTYDE, complete immunizations according to current immunization guidelines. No data are available on the response to live or inactive vaccines.

6 ADVERSE REACTIONS Most common adverse reactions (≥1%) are headache, nausea, cough, fungal infection, and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 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. The safety of ICOTYDE was evaluated in two placebo-controlled trials (Trial PSO-3 and Trial PSO-4) and two placebo- and active-controlled trials (Trial PSO-1 and Trial PSO-2) [see Clinical Studies (14) ] . A total of 2367 adults and pediatric subjects 12 years of age and older who weigh at least 40 kg with moderate-to-severe plaque psoriasis received ICOTYDE 200 mg orally once daily. Of these, 648 subjects were treated with ICOTYDE for at least one year. Data from these four trials were pooled to evaluate the safety of ICOTYDE compared to placebo for 16 weeks. Adverse Reactions Weeks 0 to 16 Table 1: Adverse Reactions that Occurred in ≥1% of Subjects in the ICOTYDE Group and More Frequently than in the Placebo Group in Trials PSO-1, PSO-2, PSO-3, and PSO-4 through Week 16 percentages based on Cochran-Mantel-Haenszel (CMH) adjusted proportions. Adverse Reactions ICOTYDE N=1296 n (%) Placebo N=568 n (%) Headache 51 (4.1) 19 (3.3) Nausea 15 (1.2) 3 (0.5) Cough 15 (1.2) 1 (0.2) Fungal Infection Fungal infection includes tinea pedis (n=4), tinea versicolor (n=2), oral candidiasis (n=2), onychomycosis (n=1), skin candida (n=1), urinary tract candidiasis (n=1), vulvovaginal candidiasis (n=1), fungal skin infection (n=1), genital infection fungal (n=1), ear infection fungal (n=1), laryngitis fungal (n=1). Two subjects experienced more than 1 event. 14 (1.1) 0 (0) Fatigue 15 (1.0) 3 (0.5) Adverse reactions that occurred in < 1% of subjects in the ICOTYDE group and at a higher rate than in the placebo group through Week 16 in Trials PSO-1, PSO-2, PSO-3, and PSO-4 were: gastritis, abdominal discomfort, and one fatal case involving upper gastrointestinal bleeding in a subject with underlying risk factors. A relationship of this event to ICOTYDE is not established. Adverse Reactions in Pediatric Subjects 12 Years of Age and Older The safety of ICOTYDE was evaluated in pediatric subjects 12 years of age and older who weigh at least 40 kg with moderate-to-severe plaque psoriasis in two placebo-controlled trials (Trial PSO-3 and Trial PSO-4). A total of 72 pediatric subjects were treated with ICOTYDE 200 mg orally once daily. Of these, 45 subjects were treated with ICOTYDE for at least one year. The adverse reactions observed in pediatric subjects were consistent with the most common adverse reactions (≥ 1%) observed in the overall population.

<table width="85%"><caption>Table 1: Adverse Reactions that Occurred in &#x2265;1% of Subjects in the ICOTYDE Group and More Frequently than in the Placebo Group in Trials PSO-1, PSO-2, PSO-3, and PSO-4 through Week 16 <footnote ID="K895">percentages based on Cochran-Mantel-Haenszel (CMH) adjusted proportions.</footnote></caption><col width="34%" align="left" valign="bottom"/><col width="33%" align="center" valign="bottom"/><col width="33%" align="center" valign="bottom"/><thead><tr><th styleCode="Lrule Rrule">Adverse Reactions</th><th styleCode="Rrule">ICOTYDE N=1296 n (%) </th><th styleCode="Rrule">Placebo N=568 n (%) </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">51 (4.1)</td><td styleCode="Rrule">19 (3.3)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nausea</td><td styleCode="Rrule">15 (1.2)</td><td styleCode="Rrule">3 (0.5)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Cough</td><td styleCode="Rrule">15 (1.2)</td><td styleCode="Rrule">1 (0.2)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Fungal Infection <footnote ID="K967">Fungal infection includes tinea pedis (n=4), tinea versicolor (n=2), oral candidiasis (n=2), onychomycosis (n=1), skin candida (n=1), urinary tract candidiasis (n=1), vulvovaginal candidiasis (n=1), fungal skin infection (n=1), genital infection fungal (n=1), ear infection fungal (n=1), laryngitis fungal (n=1). Two subjects experienced more than 1 event.</footnote></td><td styleCode="Rrule">14 (1.1)</td><td styleCode="Rrule">0 (0)</td></tr><tr><td styleCode="Lrule Rrule">Fatigue</td><td styleCode="Rrule">15 (1.0)</td><td styleCode="Rrule">3 (0.5)</td></tr></tbody></table>