Tremfya Drug Information

Plaque Psoriasis TREMFYA is indicated for the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with moderate-to-severe plaque psoriasis and who are candidates for systemic therapy or phototherapy.

Psoriatic Arthritis TREMFYA is indicated for the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with active psoriatic arthritis.

Ulcerative Colitis TREMFYA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.

Crohn's Disease TREMFYA is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.

Recommended Evaluations and Immunizations Prior to Treatment Initiation Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA. For the treatment of ulcerative colitis or Crohn's disease, obtain liver enzymes and bilirubin levels prior to initiating treatment with TREMFYA. For the treatment of plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin prior to initiating treatment with TREMFYA.

Adults The recommended dosage is 100 mg. TREMFYA may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (e.g., methotrexate). Use the lowest effective recommended dosage to maintain therapeutic response.

Preparation and Administration Instructions for Subcutaneous Injection TREMFYA is available for subcutaneous use in the following presentations: prefilled pen (TREMFYA PEN), One-Press injector, and prefilled syringes. Each prefilled pen, One-Press injector, or prefilled syringe is for one time use in one patient only. TREMFYA is intended for use under the guidance and supervision of a healthcare professional.

After proper training in subcutaneous injection technique: Adults Adults may self-inject with the TREMFYA prefilled syringe, One-Press injector, and prefilled pen. Inject into the front of the thighs, the lower abdomen except for the 2 inches around the navel, or the back of the upper arms (healthcare professional or caregiver only). Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg Pediatric self-administration is not recommended.

Administration of TREMFYA to pediatric patients with the prefilled syringe, One-Press injector and prefilled pen should be performed by a healthcare provider or by a caregiver who has received training and demonstrated proper subcutaneous injection technique. For the prefilled syringe only, injection can also be given in the back of the upper arms. Before injection, remove TREMFYA from the refrigerator and allow to reach room temperature up to 25 °C (77 °F) (30 minutes) without removing the needle cap.

Do not inject TREMFYA into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis. The TREMFYA Instructions for Use contains more detailed patient instructions on the preparation and administration of TREMFYA. If a dose is missed, administer the dose as soon as possible.

Thereafter, resume dosing at the regular scheduled time. 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 pen, One-Press injector, or prefilled syringe.

Preparation and Administration Instructions for Intravenous Infusion (Moderately to Severely Active Ulcerative Colitis and Crohn's Disease) Preparation Instructions: Withdraw and then discard 20 mL of the 0.9% Sodium Chloride Injection from the 250 mL infusion bag which is equal to the volume of TREMFYA to be added. Gently mix the diluted solution. Discard the vial with any remaining solution.

Visually inspect the diluted solution for particulate matter and discoloration before infusion. Infuse the diluted solution over a period of at least one hour. Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein binding filter (pore size 0.2 micrometer).

Do not infuse TREMFYA concomitantly in the same intravenous line with other medicinal products. Dispose any unused medicinal product in accordance with local requirements. Administration Instructions: TREMFYA solution for intravenous infusion must be diluted, prepared, and infused by a healthcare professional using aseptic technique.

TREMFYA does not contain preservatives. Storage of Diluted Solution: The diluted infusion solution may be kept at room temperature up to 25 °C (77 °F) for up to 10 hours. Storage time at room temperature begins once the diluted solution has been prepared.

The infusion should be completed within 10 hours after the dilution in the infusion bag. Do not freeze. Discard any unused portion of the infusion solution.

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 Adults with Plaque Psoriasis In clinical trials, a total of 1823 adult subjects with moderate-to-severe plaque psoriasis received TREMFYA. Weeks 0 to 16: In the 16-week placebo-controlled period of the pooled clinical trials (PsO1 and PsO2), 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.

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. Specific Adverse Reactions Infections Infections occurred in 23% of subjects in the TREMFYA group compared to 21% of subjects in the placebo group through 16 weeks of treatment. The most common (≥ 1%) infections that occurred more frequently in the TREMFYA group than in the placebo group 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.

The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%. 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. Adverse Reactions in Pediatric Subjects with Plaque Psoriasis The safety of TREMFYA was studied in one placebo- and active-controlled clinical trial (PsO5) that included 120 pediatric subjects 6 years of age and older with moderate-to-severe plaque psoriasis. The safety profile observed in pediatric subjects 6 years of age and older treated with TREMFYA up to 52 weeks was consistent with the safety profile observed in adult subjects with moderate-to-severe plaque psoriasis.

Adverse Reactions in Adults with Psoriatic Arthritis TREMFYA was studied in two placebo-controlled trials (PsA1 and PsA2) in adult subjects with psoriatic arthritis (748 subjects on TREMFYA and 372 subjects on placebo). The overall safety profile observed in adult subjects with psoriatic arthritis treated with TREMFYA is generally consistent with the safety profile in adult subjects with plaque psoriasis with the addition of bronchitis and neutrophil count decreased. In the 24-week placebo-controlled period, combined across the two studies, bronchitis occurred in 1.6% of subjects in the TREMFYA q8w group and 2.9% of subjects in the TREMFYA q4w group compared with 1.1% of subjects in the placebo group.

Neutrophil count decreased occurred in 0.3% of subjects in the TREMFYA q8w and 1.6% of subjects in the TREMFYA q4w group compared with 0% of subjects in the placebo group. The majority of events of neutrophil count decreased were mild, transient, not associated with infection and did not lead to discontinuation. A similar risk of infection and serious infections was seen in placebo-controlled trials in subjects with psoriatic arthritis as in subjects with plaque psoriasis.

TREMFYA was additionally studied in a placebo-controlled trial (PsA3) in 1054 subjects with psoriatic arthritis (668 subjects on TREMFYA and 386 subjects on placebo). The overall safety profile observed in subjects with psoriatic arthritis treated with TREMFYA in trial PsA3 is consistent with the safety profile observed in trials PsA1 and PsA2. Specific Adverse Reactions Elevated Liver Enzymes In the 24-week placebo-controlled period in trials PsA1, PsA2, and PsA3, elevated liver enzymes were reported more frequently in the TREMFYA q4w (6.1%) group compared with the q8w group (4.8%) and to the placebo group (2.8%).

Through Week 24, all events were mild to moderate in severity and none led to discontinuation of TREMFYA. Adverse Reactions in Adults with Ulcerative Colitis TREMFYA was studied up to 12 weeks in adult subjects with moderately to severely active ulcerative colitis in a randomized, double-blind, placebo-controlled induction trial (UC1) and a randomized, double-blind, placebo-controlled, induction dose-finding trial (UC3; NCT04033445). Long-term safety up to 44 weeks was evaluated in subjects who responded to induction therapy in trials UC1 or UC3 in a randomized, double-blind, placebo-controlled maintenance trial (UC2).

In a randomized, double-blind, placebo-controlled trial (UC4), subjects received subcutaneous TREMFYA at Weeks 0, 4, and 8 followed by one of two recommended subcutaneous TREMFYA dosing regimens for a total duration of up to 24 weeks. In the maintenance trial (UC2), subjects who achieved clinical response after 12 weeks of TREMFYA intravenous induction treatment were randomized and received either TREMFYA 100 mg every 8 weeks (with the first dose given at Week 4 of trial UC2) or TREMFYA 200 mg every 4 weeks (with the first dose given at Week 0 of trial UC2), by subcutaneous (SC) injection for up to an additional 44 weeks. Respiratory tract infections occurred in ≥2% of subjects treated with TREMFYA and at a higher rate than placebo (8.8% TREMFYA-treated subjects vs. 7.3% placebo-treated subjects) through Week 12 in the induction trials (UC1 and UC3).

Respiratory tract infections included COVID-19, influenza, nasopharyngitis, respiratory tract infection, upper respiratory tract infection, and viral respiratory tract infection. Adverse reactions that occurred in ≥3% of subjects treated with TREMFYA and at a higher rate than placebo through Week 44 in the maintenance trial (UC2) are shown in Table 2. Adverse reactions reported in trial UC4 through Week 24 in ≥3% of subjects treated with either subcutaneous TREMFYA dosing regimen and at a higher rate than placebo are shown in Table 3.

In the 24-week trial (UC4), serious infections occurred in 1.8% of subjects treated with TREMFYA versus 0.7% of subjects in the placebo group. Adverse Reactions in Adults with Crohn's Disease TREMFYA was studied in four clinical trials in adult subjects with moderately to severely active Crohn's disease. Through Week 12 in trials CD1, CD2, and CD4; headache (including headache, migraine, and sinus headache) was reported in ≥3% of subjects treated with intravenous TREMFYA and at a greater rate than placebo (3.4% TREMFYA-treated subjects vs. 1.9% placebo-treated subjects).

In TREMFYA-treated subjects in trial CD2, one case of active extrapulmonary TB was reported between Weeks 12–48 and one case of active pulmonary TB was reported after Week 48. Both subjects had negative baseline screenings and resided in TB-endemic regions. In general, the safety profile in subjects treated with subcutaneous TREMFYA from Week 12 up to Week 48 in these trials was generally similar to that reported with intravenous TREMFYA through Week 12.

Trial CD3 In trial CD3, 347 subjects were enrolled, of whom 230 subjects were randomized to receive TREMFYA. These elevations occurred without concomitant elevations in total bilirubin.

Postmarketing Experience

The following adverse reactions have been reported during post-approval of TREMFYA. Because these reactions 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 TREMFYA exposure. Immune system disorders: Hypersensitivity, including anaphylaxis Skin and subcutaneous tissue disorders: Rash

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 trial in subjects with moderate-to-severe plaque 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 trial.

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.

Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to Tremfya during pregnancy. Patients should be encouraged to enroll in the registry by visiting www.mothertobaby.org/ongoing-study/tremfya-guselkumab, by calling 1-877-311-8972, or emailing [email protected]. Risk Summary Available data from literature, post-marketing reports, and ongoing pregnancy registry with Tremfya use in pregnant women are insufficient to establish 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 ). 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 18 times the exposure (AUC) in humans administered 200 mg intravenously and 16 times the exposure (AUC) to the 400 mg dose given subcutaneously. The clinical significance of these nonclinical findings 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 respectively.

Clinical Considerations Disease-associated Maternal and Embryo/Fetal Risk Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses and peaks during the third trimester.

Therefore, Tremfya may be present in infants exposed in utero. The potential clinical impact of guselkumab exposure in infants exposed in utero should be considered. 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 from the beginning of organogenesis to parturition at a dose (50 mg/kg) resulting in exposures (AUC) 18 times the exposure in humans administered 200 mg intravenously and 16 times the human exposure at 400 mg given subcutaneously.

No guselkumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.

Pediatric Use Plaque Psoriasis The safety and effectiveness of TREMFYA for the treatment of moderate-to-severe plaque psoriasis have been established in pediatric patients 6 years of age and older who are candidates for systemic therapy or phototherapy. The safety and effectiveness of TREMFYA have not been established in pediatric patients with plaque psoriasis who are younger than 6 years of age. Psoriatic Arthritis The safety and effectiveness of TREMFYA have been established for treatment of active psoriatic arthritis in pediatric patients 6 years of age and older.

Use of TREMFYA in this age group is supported by evidence from adequate and well controlled trials of TREMFYA in adults with plaque psoriasis and psoriatic arthritis, pharmacokinetic data from adult subjects with plaque psoriasis and psoriatic arthritis and pediatric subjects with plaque psoriasis, and safety data from a clinical trial in 120 subjects 6 to 17 years of age with plaque psoriasis. The observed pre-dose (trough) concentrations are generally comparable between adult subjects with plaque psoriasis, adult subjects with psoriatic arthritis and pediatric subjects with plaque psoriasis, and the systemic exposure is expected to be comparable between adult and pediatric patients with psoriatic arthritis. Ulcerative Colitis The safety and effectiveness of TREMFYA have not been established in pediatric patients with ulcerative colitis.

Crohn's Disease The safety and effectiveness of TREMFYA have not been established in pediatric patients with Crohn's disease.

TREMFYA is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients.