Prescription Drugs

TREMFYA (guselkumab) Injection DESCRIPTION Guselkumab, an interleukin-23 blocker, is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. Guselkumab is produced in a mammalian cell line using recombinant DNA technology. TREMFYA (guselkumab) Injection is a sterile, preservative free, clear, colorless to light yellow solution that may contain small translucent particles. Each single-dose prefilled syringe for subcutaneous use contains 100 mg of guselkumab in 1 mL. TREMFYA is supplied as a single-dose solution in a 1 mL glass syringe with a 27G, half inch fixed needle assembled in a passive needle guard delivery system. Each TREMFYA prefilled syringe delivers 1 mL of solution containing guselkumab (100 mg), L-histidine (0.6 mg), L-histidine monohydrochloride monohydrate (1.5 mg), polysorbate 80 (0.5 mg), sucrose (79 mg) and water for injection at pH 5.8.

INDICATIONS TREMFYA™ is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. DOSAGE AND ADMINISTRATION Dosage TREMFYA is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter. Tuberculosis Assessment Prior To Initiation Of TREMFYA Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA [see WARNINGS AND PRECAUTIONS]. Important Administration Instructions Administer TREMFYA subcutaneously. Each prefilled syringe is for single-dose only. Instruct patients to inject the full amount (1 mL), which provides 100 mg of TREMFYA. Do not inject TREMFYA into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis [see Instructions For Use]. TREMFYA is intended for use under the guidance and supervision of a physician. TREMFYA may be administered by a health care professional, or a patient may self-inject after proper training in subcutaneous injection technique. The TREMFYA Instructions for Use contains more detailed patient instructions on the preparation and administration of TREMFYA [see Instructions For Use]. Preparation For Use Of TREMFYA Prefilled Syringe Before injection, remove TREMFYA prefilled syringe from the refrigerator and allow TREMFYA to reach room temperature (30 minutes) without removing the needle cap. Inspect TREMFYA visually for particulate matter and discoloration prior to administration. TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. Do not use if the liquid contains large particles, is discolored or cloudy. TREMFYA does not contain preservatives; therefore, discard any unused product remaining in the prefilled syringe. HOW SUPPLIED Dosage Forms And Strengths Injection: 100 mg/mL in a single-dose prefilled syringe TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. TREMFYA (guselkumab) Injection is a clear and colorless to light yellow solution that may contain small translucent particles. TREMFYA is supplied as a single-dose 100 mg/mL prefilled syringe: NDC CODE: 57894-640-01 Storage And Handling TREMFYA is sterile and preservative-free. Discard any unused portion. Store in a refrigerator at 2°C to 8°C (36°F to 46°F) Store in original carton until time of use Protect from light until use. Do not freeze. Do not shake Manufactured by: Janssen Biotech, Inc Horsham, PA 19044. Revised: July 2017.

SIDE EFFECTS The following adverse reactions are discussed in greater detail in other sections of labeling: Infections [see WARNINGS AND PRECAUTIONS] 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. In clinical trials, a total of 1748 subjects with moderate-to-severe plaque psoriasis received TREMFYA. Of these, 1393 subjects were exposed to TREMFYA for at least 6 months and 728 subjects were exposed for at least 1 year. Data from two placebo-and active-controlled trials (VOYAGE 1 and VOYAGE 2) in 1441 subjects (mean age 44 years; 70% males; 82% white) were pooled to evaluate the safety of TREMFYA (100 mg administered subcutaneously at Weeks 0 and 4, followed by every 8 weeks). Weeks 0 To 16 In the 16-week placebo-controlled period of the pooled clinical trials (VOYAGE 1 and VOYAGE 2), adverse events occurred in 49% of subjects in the TREMFYA group compared to 47% of subjects in the placebo group and 49% of subjects in the U.S. licensed adalimumab group. Serious adverse events occurred in 1.9% of the TREMFYA group (6.3 events per 100 subject-years of follow-up) compared to 1.4% of the placebo group (4.7 events per 100 subject-years of follow-up), and in 2.6% of U.S. licensed adalimumab group (9.9 events per 100 subject-years of follow-up). Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TREMFYA group than in the placebo group during the 16-week placebo-controlled period. Table 1: Adverse Reactions Occurring in ≥ 1% of Subjects through Week 16 in VOYAGE 1 and VOYAGE 2 TREMFYAa 100 mg N=823 n (%) Adalimumabb N=196 n (%) Placebo N=422 n (%) Upper respiratory infectionsc 118 (14.3) 21 (10.7) 54 (12.8) Headached 38 (4.6) 2 (1.0) 14 (3.3) Injection site reactionse 37 (4.5) 15 (7.7) 12 (2.8) Arthralgia 22 (2.7) 4 (2.0) 9 (2.1) Diarrhea 13 (1.6) 3 (1.5) 4 (0.9) Gastroenteritisf 11 (1.3) 4 (2.0) 4 (0.9) Tinea infectionsg 9 (1.1) 0 0 Herpes simplex infectionsh 9 (1.1) 0 2 (0.5) a subjects receiving 100 mg of TREMFYA at Week 0, Week 4, and every 8 weeks thereafter b U.S. licensed adalimumab c Upper respiratory infections include nasopharyngitis, upper respiratory tract infection (URTI), pharyngitis, and viral URTI. d Headache includes headache and tension headache. e Injection site reactions include injection site erythema, bruising, hematoma, hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria. f Gastroenteritis includes gastroenteritis and viral gastroenteritis. g Tinea infections include tinea pedis, tinea cruris, tinea infection, and tinea manuum infections. h Herpes simplex infections include oral herpes, herpes simplex, genital herpes, genital herpes simplex, and nasal herpes simplex. Adverse reactions that occurred in < 1% but > 0.1% of subjects in the TREMFYA group and at a higher rate than in the placebo group through Week 16 in VOYAGE 1 and VOYAGE 2 were migraine, candida infections, and urticaria. Specific Adverse Reactions Infections Infections occurred in 23% of the TREMFYA group compared to 21% of the placebo group. The most common ( ≥ 1%) infections were upper respiratory infections, gastroenteritis, tinea infections, and herpes simplex infections; all cases were mild to moderate in severity and did not lead to discontinuation of TREMFYA. Elevated Liver Enzymes Elevated liver enzymes were reported more frequently in the TREMFYA group (2.6%) than in the placebo group (1.9%). Of the 21 subjects who were reported to have elevated liver enzymes in the TREMFYA group, all events except one were mild to moderate in severity and none of the events led to discontinuation of TREMFYA. Safety Through Week 48 Through Week 48, no new adverse reactions were identified with TREMFYA use and the frequency of the adverse reactions was similar to the safety profile observed during the first 16 weeks of treatment. Immunogenicity As with all therapeutic proteins, there is the potential for immunogenicity with TREMFYA. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to guselkumab with the incidences of antibodies to other products may be misleading. Up to Week 52, approximately 6% of subjects treated with TREMFYA developed antidrug antibodies. Of the subjects who developed antidrug antibodies, approximately 7% had antibodies that were classified as neutralizing antibodies. Among the 46 subjects who developed antibodies to guselkumab and had evaluable data, 21 subjects exhibited lower trough levels of guselkumab, including one subject who experienced loss of efficacy after developing high antibody titers. However, antibodies to guselkumab were generally not associated with changes in clinical response or development of injection-site reactions. DRUG INTERACTIONS Live Vaccinations Avoid use of live vaccines in patients treated with TREMFYA [see WARNINGS AND PRECAUTIONS]. CYP450 Substrates The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, interferon) during chronic inflammation. Results from an exploratory drug-drug interaction study in subjects with moderate-to-severe psoriasis suggested a low potential for clinically relevant drug interactions for drugs metabolized by CYP3A4, CYP2C9, CYP2C19 and CYP1A2 but the interaction potential cannot be ruled out for drugs metabolized by CYP2D6. However, the results were highly variable because of the limited number of subjects in the study. Upon initiation of TREMFYA in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment as needed [see CLINICAL PHARMACOLOGY].

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Infections TREMFYA may increase the risk of infection. In clinical trials, infections occurred in 23% of subjects in the TREMFYA group versus 21% of subjects in the placebo group through 16 weeks of treatment. Upper respiratory tract infections, gastroenteritis, tinea infections, and herpes simplex infections occurred more frequently in the TREMFYA group than in the placebo group [see ADVERSE REACTIONS]. The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%. Treatment with TREMFYA 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 TREMFYA. 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 discontinue TREMFYA until the infection resolves. Pre-treatment Evaluation For Tuberculosis Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA. Initiate treatment of latent TB prior to administering TREMFYA. In clinical studies, 105 subjects with latent TB who were concurrently treated with TREMFYA and appropriate TB prophylaxis did not develop active TB (during the mean follow-up of 43 weeks). Monitor patients for signs and symptoms of active TB during and after TREMFYA treatment. Consider anti-TB therapy prior to initiating TREMFYA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Do not administer TREMFYA to patients with active TB infection. Immunizations Prior to initiating therapy with TREMFYA, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TREMFYA. No data are available on the response to live or inactive vaccines. Patient Counseling Information Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before starting TREMFYA therapy, and each time the prescription is renewed, as there may be new information they need to know. Infections Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any symptoms of an infection [see WARNINGS AND PRECAUTIONS]. Instruction On Injection Technique Instruct the patient or caregivers to perform the first self-injection under the supervision and guidance of a qualified healthcare professional for proper training in subcutaneous injection technique. Instruct patients who are self-administering to inject the full dose of TREMFYA [see Medication Guide and Instructions for Use]. Instruct patients or caregivers in the technique of proper needle and syringe disposal. Needles and syringes should be disposed of in a puncture-resistant container. Advise patients and caregivers not to reuse needles or syringes. Remind patients if they forget to take their dose of TREMFYA to inject their dose as soon as they remember. They should then take their next dose at the appropriate scheduled time. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of TREMFYA. No effects on fertility parameters were observed after male guinea pigs were subcutaneously administered guselkumab at a dose of 25 mg/kg twice weekly (15 times the MRHD based on a mg/kg comparison). No effects on fertility parameters were observed after female guinea pigs were subcutaneously administered guselkumab at doses up to 100 mg/kg twice-weekly (60 times the MRHD based on a mg/kg comparison). Use In Specific Populations Pregnancy Risk Summary There are no available data on TREMFYA use in pregnant women to inform a drug associated risk of adverse developmental outcomes. Human IgG antibodies are known to cross the placental barrier; therefore, TREMFYA may be transmitted from the mother to the developing fetus. In a combined embryofetal development and pre-and post-natal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of guselkumab during organogenesis through parturition at doses up to 30 times the maximum recommended human dose (MRHD). Neonatal deaths were observed at 6-to 30-times the MRHD (see Data). The clinical significance of these nonclinical findings is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated 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% to 4% and 15% to 20%, respectively. Data Animal Data In a combined embryofetal development and pre-and post-natal development study, pregnant cynomolgus monkeys were administered weekly subcutaneous doses of guselkumab up to 50 mg/kg (30 times the MRHD based on a mg/kg comparison) from the beginning of organogenesis to parturition. Neonatal deaths occurred in the offspring of one control monkey, three monkeys administered guselkumab at 10 mg/kg/week (6 times the MRHD based on a mg/kg comparison) and three monkeys administered guselkumab at 50 mg/kg/week (30 times the MRHD based on a mg/kg comparison). The clinical significance of these findings is unknown. No guselkumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age. Lactation Risk Summary There are no data on the presence of guselkumab in human milk, the effects on the breastfed infant, or the effects on milk production. Guselkumab was not detected in the milk of lactating cynomolgus monkeys. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TREMFYA and any potential adverse effects on the breastfed infant from TREMFYA or from the underlying maternal condition. Pediatric Use The safety and efficacy of TREMFYA in pediatric patients (less than 18 years of age) have not been established. Geriatric Use Of the 1748 subjects with plaque psoriasis exposed to TREMFYA, a total of 93 subjects were 65 years or older, and 4 subjects were 75 years or older. No overall differences in safety or effectiveness were observed between older and younger subjects who received TREMFYA. However, the number of subjects aged 65 years and older was not sufficient to determine whether they respond differently from younger subjects [see CLINICAL PHARMACOLOGY].