Johnson & Johnson submits applications to FDA for TREMFYA approval in pediatric psoriasis; treatment targets children aged 6 and older with plaque psoriasis and age 5 and older with juvenile psoriatic arthritis

SPRING HOUSE, Pa. (December 2, 2024) – Johnson & Johnson today announced the submission of two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) seeking approval of TREMFYA^® (guselkumab) for the treatment of children 6 years and older with moderate-to-severe plaque psoriasis (PsO) and children 5 years of age and older with active juvenile psoriatic arthritis (jPsA).^a

The PsO submission is based on data from the Phase 3 PROTOSTAR study in pediatric patients with moderate to severe plaque PsO and bridging pharmacokinetic (PK) data from the Phase 3 VOYAGE 1 and 2 studies in adult patients with moderate to severe plaque PsO. The jPsA submission is based on PK extrapolation analyses from adult PsA studies (DISCOVER 1 and 2) and TREMFYA efficacy and safety data from the PROTOSTAR study.^b

“This milestone underscores our commitment to transform the standard of care for patients of all ages and builds on our expertise and legacy in IL-23 and immune-mediated diseases,” said Liza O’Dowd, M.D., Vice President, Immunodermatology Disease Area Leader, Johnson & Johnson Innovative Medicine. “There is a critical gap in the treatment of children and adolescents with these skin and joint conditions, where debilitating symptoms can present challenges related to physical appearance and ability to function. At Johnson & Johnson, we are working to address this gap by investigating the efficacy and well-characterized safety profile of TREMFYA for pediatric patients.”

TREMFYA^® is the first approved monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is an important driver of immune-mediated diseases such as plaque PsO and PsA.

Editor’s Notes:
a. TREMFYA^® is not currently approved to treat moderate to severe pediatric plaque psoriasis or active juvenile psoriatic arthritis (jPsA).
b. Data extrapolation is the process of estimating future trends or effects based on previous observations. With limited pediatric patients available for clinical trial inclusion, researchers can extrapolate data from adult patient trials to determine the potential efficacy and tolerability of a treatment for the pediatric population.

ABOUT PEDIATRIC PLAQUE PSORIASIS
Plaque psoriasis (PsO) is an immune-mediated disease resulting in overproduction of skin cells, which causes inflamed, scaly plaques that may be itchy or painful.[i] Almost one-third of PsO cases begin in childhood, with roughly 20,000 children under 10 diagnosed with psoriasis each year^.1 Having visible skin disease can be highly stressful for children and adolescents and can have a long-term impact on those affected.²

ABOUT JUVENILE PSORIATIC ARTHRITIS
Juvenile psoriatic arthritis (jPsA) is a form of juvenile idiopathic arthritis (JIA) characterized by chronic joint inflammation, swelling and psoriasis. Juvenile PsA is relatively rare, accounting for approximately 5% of the JIA population. In many cases, the skin manifestations start before the arthritis.³

ABOUT THE PHASE 3 PROTOSTAR STUDY (NCT03451851)
PROTOSTAR is a Phase 3, multicenter, randomized, placebo- and active comparator-controlled study evaluating the efficacy, safety, and pharmacokinetics of subcutaneously administered TREMFYA^® for the treatment of chronic plaque psoriasis in pediatric patients six years of age and older. Co-primary endpoints of the study were Investigator’s Global Assessment (IGA) 0/1 and PASI 75 at Week 16.⁴

ABOUT THE PHASE 3 VOYAGE STUDIES (NCT02207231 and NCT02207244)
VOYAGE 1 and 2 were Phase 3 randomized, double-blind, placebo- and active comparator-controlled studies designed to evaluate the efficacy and safety of TREMFYA^® compared with placebo and adalimumab in adults with moderate to severe plaque PsO. The co-primary endpoints of the studies were the proportions of patients receiving TREMFYA^® versus patients receiving placebo achieving Investigator’s Global Assessment (IGA) 0/1 (clear/almost clear skin) and PASI 90 at week 16.^5,6

ABOUT THE PHASE 3 DISCOVER STUDIES (NCT03162796 and NCT03158285)
DISCOVER-1 was a Phase 3, multicenter, randomized, double-blind study evaluating the efficacy and safety of TREMFYA^® administered by subcutaneous injection in participants with active PsA, including those previously treated with one to two tumor necrosis factor inhibitors (TNFi). The primary endpoint was response of ACR20 at week 24.⁷ DISCOVER-2 was a Phase 3, multicenter, randomized, double-blind study evaluating the efficacy and safety of TREMFYA^® administered by subcutaneous injection in biologic-naïve patients with active PsA. The primary endpoint was response of ACR20 at week 24.⁸

ABOUT TREMFYA^® (guselkumab)
Developed by Johnson & Johnson, TREMFYA^® is the first approved fully-human, dual-acting monoclonal antibody designed to neutralize inflammation at the cellular source by blocking IL-23 and binding to CD64 (a receptor on cell that produce IL-23). Findings for dual-acting are limited to in vitro studies that demonstrate guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model. The clinical significance of this finding is not known.

TREMFYA^® is a prescription medicine approved in the U.S. to treat:
· adults with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light).
· adults with active psoriatic arthritis.
· adults with moderately to severely active ulcerative colitis.⁹

TREMFYA^® is approved Europe, Canada, Japan, and a number of other countries for the treatment of adults with moderate-to-severe plaque psoriasis and for the treatment of adults with active psoriatic arthritis.

Johnson & Johnson maintains exclusive worldwide marketing rights to TREMFYA^®. For more information, visit: www.tremfya.com.

TREMFYA^® is a prescription medicine that may cause serious side effects, including:

• Serious Allergic Reactions. Stop using TREMFYA^® and get emergency medical help right away if you develop any of the following symptoms of a serious allergic reaction:

• Infections. TREMFYA^® may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with TREMFYA^® and may treat you for TB before you begin treatment with TREMFYA^® if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with TREMFYA^®.

Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including:

Do not take TREMFYA^® if you have had a serious allergic reaction to guselkumab or any of the ingredients in TREMFYA^®.

Before using TREMFYA^®, tell your healthcare provider about all of your medical conditions, including if you:

• have any of the conditions or symptoms listed in the section “What is the most important information I should know about TREMFYA^®?”
• have an infection that does not go away or that keeps coming back.
• have TB or have been in close contact with someone with TB.
• have recently received or are scheduled to receive an immunization (vaccine). You should avoid receiving live vaccines during treatment with TREMFYA^®.
• are pregnant or plan to become pregnant. It is not known if TREMFYA^® can harm your unborn baby.
  Pregnancy Registry: If you become pregnant during treatment with TREMFYA^®, talk to your healthcare provider about registering in the pregnancy exposure registry for TREMFYA^®. You can enroll by visiting www.mothertobaby.org/ongoing-study/tremfya-guselkumab, by calling 1-877-311-8972, or emailing MotherToBaby@health.ucsd.edu. The purpose of this registry is to collect information about the safety of TREMFYA^® during pregnancy.
• are breastfeeding or plan to breastfeed. It is not known if TREMFYA^® passes into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of TREMFYA^® include: respiratory tract infections, headache, injection site reactions, joint pain (arthralgia), diarrhea, stomach flu (gastroenteritis), fungal skin infections, herpes simplex infections, and bronchitis.

These are not all the possible side effects of TREMFYA^®. Call your doctor for medical advice about side effects.

Use TREMFYA^® exactly as your healthcare provider tells you to use it.

Please read the full Prescribing InformationHIGHLIGHTS OF PRESCRIBING INFORMATION TREMFYA® (guselkumab) These highlights do not include all the information needed to use TREMFYA safely and effectively. See full prescribing information for TREMFYA. --------------------------- DOSAGE FORMS AND STRENGTHS --------------------------- TREMFYA® (guselkumab) injection, for subcutaneous use Subcutaneous Injection (3) TREMFYA® PEN (guselkumab) injection, for subcutaneous use • Injection: 100 mg/mL in a single-dose One-Press patient-controlled injector. TREMFYA® (guselkumab) injection, for intravenous use • Injection: 200 mg/2 mL in a single-dose prefilled pen (TREMFYA PEN). Initial U.S. Approval: 2017 • Injection: 100 mg/mL in a single-dose prefilled syringe. -------------------------------- RECENT MAJOR CHANGES -------------------------------- • Injection: 200 mg/2 mL in a single-dose prefilled syringe. Indications and Usage (1.3) 09/2024 Intravenous Infusion (3) Dosage and Administration (2.1, 2.4, 2.5, 2.6) 09/2024 • Injection: 200 mg/20 mL (10 mg/mL) solution in a single-dose vial. Warnings and Precautions (5.2, 5.3, 5.4) 09/2024 ----------------------------------- CONTRAINDICATIONS ----------------------------------- Serious hypersensitivity reactions to guselkumab or to any of the excipients. (4) ----------------------------------INDICATIONS AND USAGE------------------------------- TREMFYA is an interleukin-23 antagonist indicated for the treatment of adult -----------------------------WARNINGS AND PRECAUTIONS ----------------------------- patients with: • Hypersensitivity Reactions: Serious hypersensitivity reactions, including • moderate-to-severe plaque psoriasis who are candidates for systemic therapy anaphylaxis, may occur. (5.1) or phototherapy (1.1) • Infections: TREMFYA may increase the risk of infection. Do not initiate treatment • active psoriatic arthritis (1.2) with TREMFYA in patients with clinically important active infection until the • moderately to severely active ulcerative colitis (1.3) infection resolves or is adequately treated. If such an infection develops, discontinue TREMFYA until the infection resolves. (5.2) -----------------------------DOSAGE AND ADMINISTRATION----------------------------- • Tuberculosis (TB): Evaluate for TB prior to initiating treatment with TREMFYA. (5.3) • Complete all age-appropriate vaccinations as recommended by current • Immunizations: Avoid use of live vaccines. (5.4) immunization guidelines prior to treatment initiation. (2.1) ----------------------------------- ADVERSE REACTIONS ----------------------------------- Recommended Dosage Most common adverse reactions associated with TREMFYA are: Plaque Psoriasis • Plaque Psoriasis and Psoriatic Arthritis (≥1%): upper respiratory infections, • 100 mg administered by subcutaneous injection at Week 0, Week 4, and every headache, injection site reactions, arthralgia, bronchitis, diarrhea, 8 weeks thereafter. (2.2) gastroenteritis, tinea infections, and herpes simplex infections. (6.1) Psoriatic Arthritis • Ulcerative Colitis • 100 mg administered by subcutaneous injection at Week 0, Week 4, and every • Induction (≥2%): respiratory tract infections. (6.1) 8 weeks thereafter. TREMFYA can be used alone or in combination with a • Maintenance (≥3%): injection site reactions, arthralgia, and upper respiratory conventional DMARD (e.g., methotrexate). (2.3) tract infection. (6.1) Ulcerative Colitis • Induction: 200 mg administered by intravenous infusion over at least one hour at Week 0, Week 4, and Week 8. (2.4) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. • Maintenance: 100 mg administered by subcutaneous injection at Week 16, and at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. every 8 weeks thereafter, or 200 mg administered by subcutaneous injection at See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Week 12, and every 4 weeks thereafter. Use the lowest effective recommended Revised: 09/2024 dosage to maintain therapeutic response. (2.4) FULL PRESCRIBING INFORMATION: CONTENTS* 8 USE IN SPECIFIC POPULATIONS 1 INDICATIONS AND USAGE 8.1 Pregnancy 1.1 Plaque Psoriasis 8.2 Lactation 1.2 Psoriatic Arthritis 8.4 Pediatric Use 1.3 Ulcerative Colitis 8.5 Geriatric Use 2 DOSAGE AND ADMINISTRATION 11 DESCRIPTION 2.1 R ecommended Evaluations and Immunizations Prior to Treatment 12 CLINICAL PHARMACOLOGY Initiation 12.1 Mechanism of Action 2.2 Recommended Dosage for Plaque Psoriasis 12.2 Pharmacodynamics 2.3 Recommended Dosage for Psoriatic Arthritis 12.3 Pharmacokinetics 2.4 Recommended Dosage for Ulcerative Colitis 12.6 Immunogenicity 2.5 Preparation and Administration Instructions for Subcutaneous Injection 13 NONCLINICAL TOXICOLOGY 2.6 P reparation and Administration Instructions for Intravenous Infusion 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility (Ulcerative Colitis) 14 CLINICAL STUDIES 3 DOSAGE FORMS AND STRENGTHS 14.1 Plaque Psoriasis 4 CONTRAINDICATIONS 14.2 Psoriatic Arthritis 5 WARNINGS AND PRECAUTIONS 14.3 Ulcerative Colitis 5.1 Hypersensitivity Reactions 16 HOW SUPPLIED/STORAGE AND HANDLING 5.2 Infections 16.1 How Supplied 5.3 Pre-treatment Evaluation for Tuberculosis 16.2 Storage and Handling 5.4 Immunizations 17 PATIENT COUNSELING INFORMATION 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience *Sections or subsections omitted from the full prescribing information are not 6.2 Postmarketing Experience listed. 7 DRUG INTERACTIONS 7.1 CYP450 Substrates FULL PRESCRIBING INFORMATION 2 DOSAGE AND ADMINISTRATION 1 INDICATIONS AND USAGE 2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation 1.1 Plaque Psoriasis • Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA is indicated for the treatment of adult patients with moderate-to-severe TREMFYA [see Warnings and Precautions (5.3)]. plaque psoriasis who are candidates for systemic therapy or phototherapy. • Complete all age-appropriate vaccinations according to current immunization 1.2 Psoriatic Arthritis guidelines [see Warnings and Precautions (5.4)]. TREMFYA is indicated for the treatment of adult patients with active psoriatic arthritis. 2.2 Recommended Dosage for Plaque Psoriasis TREMFYA is administered by subcutaneous injection. The recommended dosage is 1.3 Ulcerative Colitis 100 mg at Week 0, Week 4, and every 8 weeks thereafter. TREMFYA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis. 1 TREMFYA® (guselkumab) TREMFYA® (guselkumab) 2.3 Recommended Dosage for Psoriatic Arthritis 3 DOSAGE FORMS AND STRENGTHS TREMFYA is administered by subcutaneous injection. The recommended dosage is TREMFYA/TREMFYA PEN is a clear and colorless to light yellow solution. 100 mg at Week 0, Week 4, and every 8 weeks thereafter. Subcutaneous Injection TREMFYA may be administered alone or in combination with a conventional • Injection: 100 mg/mL in a single-dose One-Press patient-controlled injector. disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate). • Injection: 200 mg/2 mL in a single-dose prefilled pen (TREMFYA PEN). 2.4 Recommended Dosage for Ulcerative Colitis • Injection: 100 mg/mL in a single-dose prefilled syringe. Induction: • Injection: 200 mg/2 mL in a single-dose prefilled syringe. The recommended induction dosage of TREMFYA is 200 mg administered by Intravenous Infusion intravenous infusion over at least one hour at Week 0, Week 4, and Week 8 [see Dosage and Administration (2.6)]. • Injection: 200 mg/20 mL (10 mg/mL) solution in a single-dose vial. Maintenance: 4 CONTRAINDICATIONS TREMFYA is contraindicated in patients with a history of serious hypersensitivity The recommended maintenance dosage of TREMFYA/TREMFYA PEN is: reaction to guselkumab or to any of the excipients [see Warnings and Precautions • 100 mg administered by subcutaneous injection at Week 16, and every 8 weeks (5.1)]. thereafter, or • 200 mg administered by subcutaneous injection at Week 12, and every 4 weeks 5 WARNINGS AND PRECAUTIONS thereafter. 5.1 Hypersensitivity Reactions Use the lowest effective recommended dosage to maintain therapeutic response. Serious hypersensitivity reactions, including anaphylaxis, have been reported with post market use of TREMFYA. Some cases required hospitalization. If a 2.5 Preparation and Administration Instructions for Subcutaneous Injection serious hypersensitivity reaction occurs, discontinue TREMFYA and initiate • Administer TREMFYA/TREMFYA PEN subcutaneously. Each prefilled syringe, appropriate therapy. One-Press injector, or Prefilled Pen is for one time use in one patient only. Instruct patients to inject the full amount (1 mL or 2 mL), which provides 100 mg 5.2 Infections or 200 mg of TREMFYA. TREMFYA may increase the risk of infection. In clinical trials in subjects with • TREMFYA/TREMFYA PEN is intended for use under the guidance and supervision plaque psoriasis, infections occurred in 23% of subjects in the TREMFYA group of a healthcare professional. TREMFYA/TREMFYA PEN may be administered by versus 21% of subjects in the placebo group through 16 weeks of treatment. Upper a healthcare professional, or a patient/caregiver may inject after proper training respiratory tract infections, gastroenteritis, tinea infections, and herpes simplex on correct subcutaneous injection technique. infections occurred more frequently in the TREMFYA group than in the placebo • Before injection, remove TREMFYA/TREMFYA PEN from the refrigerator and group [see Adverse Reactions (6.1)]. The rate of serious infections for the TREMFYA allow to reach room temperature (30 minutes) without removing the needle cap. group and the placebo group was ≤ 0.2%. A similar risk of infection was seen in • Inject into the front of the thighs, the lower abdomen except for the 2 inches placebo-controlled trials in subjects with psoriatic arthritis and ulcerative colitis. around the navel, or the back of the upper arms (healthcare professional or Treatment with TREMFYA should not be initiated in patients with any clinically caregiver only). important active infection until the infection resolves or is adequately treated. • Do not inject TREMFYA/TREMFYA PEN into areas where the skin is tender, In patients with a chronic infection or a history of recurrent infection, consider the bruised, red, hard, thick, scaly, or affected by psoriasis [see Instructions for risks and benefits prior to prescribing TREMFYA. Instruct patients to seek medical Use]. help if signs or symptoms of clinically important chronic or acute infection occur. • The TREMFYA/TREMFYA PEN Instructions for Use contains more detailed If a patient develops a clinically important or serious infection or is not responding patient instructions on the preparation and administration of TREMFYA/ to standard therapy, monitor the patient closely and discontinue TREMFYA until the TREMFYA PEN [see Instructions for Use]. infection resolves. • If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time. 5.3 Pre-treatment Evaluation for Tuberculosis • Inspect TREMFYA/TREMFYA PEN visually for particulate matter and Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with discoloration prior to administration. TREMFYA/TREMFYA PEN is a clear and TREMFYA. Initiate treatment of latent TB prior to administering TREMFYA. In clinical colorless to light yellow solution that may contain small translucent particles. Do trials, 105 subjects with plaque psoriasis, 71 subjects with psoriatic arthritis, and not use if the liquid contains large particles, is discolored or cloudy. TREMFYA/ 31 subjects with ulcerative colitis with latent TB who were concurrently treated TREMFYA PEN does not contain preservatives; therefore, discard any unused with TREMFYA and appropriate TB prophylaxis did not develop active TB. Monitor product remaining in the prefilled syringe, One-Press injector, or Prefilled Pen. patients for signs and symptoms of active TB during and after TREMFYA treatment. 2.6 Preparation and Administration Instructions for Intravenous Infusion Consider anti-TB therapy prior to initiating TREMFYA in patients with a past (Ulcerative Colitis) history of latent or active TB in whom an adequate course of treatment cannot be Preparation Instructions: confirmed. Do not administer TREMFYA to patients with active TB infection. 1. Withdraw and then discard 20 mL of the 0.9% Sodium Chloride Injection from 5.4 Immunizations the 250 mL infusion bag which is equal to the volume of TREMFYA to be added. Avoid use of live vaccines in patients treated with TREMFYA. Medications that 2. Withdraw 20 mL of TREMFYA from the vial and add it to the 250 mL intravenous interact with the immune system may increase the risk of infection following infusion bag of 0.9% Sodium Chloride Injection for a final concentration of 0.8 mg/mL. administration of live vaccines. Prior to initiating therapy with TREMFYA, complete Gently mix the diluted solution. Discard the vial with any remaining solution. all age-appropriate vaccinations according to current immunization guidelines. No 3. Visually inspect the diluted solution for particulate matter and discoloration data are available on the response to live or inactive vaccines. before infusion. Infuse the diluted solution over a period of at least one hour. 4. Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein 6 ADVERSE REACTIONS binding filter (pore size 0.2 micrometer). The following adverse reactions are discussed in greater detail in other sections 5. Do not infuse TREMFYA concomitantly in the same intravenous line with other of labeling: medicinal products. • Hypersensitivity Reactions [see Contraindications (4) and Warnings and 6. Dispose any unused medicinal product in accordance with local requirements. Precautions (5.1)] Administration Instructions: • Infections [see Warnings and Precautions (5.2)] • T REMFYA solution for intravenous infusion must be diluted, prepared, and 6.1 Clinical Trials Experience infused by a healthcare professional using aseptic technique. TREMFYA does Because clinical trials are conducted under widely varying conditions, adverse not contain preservatives. Each vial is for one time use in one patient only. reaction rates observed in the clinical trials of a drug cannot be directly compared • I nspect TREMFYA visually for particulate matter and discoloration prior to to rates in the clinical trials of another drug and may not reflect the rates observed administration. TREMFYA is a clear and colorless to light yellow solution that in practice. may contain small translucent particles. Do not use if the liquid contains large particles, is discolored, or is cloudy. Plaque Psoriasis In clinical trials, a total of 1823 subjects with moderate-to-severe plaque psoriasis Storage of Diluted Solution: received TREMFYA. Of these, 1393 subjects were exposed to TREMFYA for at least • T he diluted infusion solution may be kept at room temperature up to 25°C (77°F) 6 months and 728 subjects were exposed for at least 1 year. 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 Data from two placebo- and active-controlled trials (PsO1 and PsO2) in 1441 after the dilution in the infusion bag. subjects (mean age 44 years; 70% males; 82% white) were pooled to evaluate • D o not freeze. the safety of TREMFYA (100 mg administered subcutaneously at Weeks 0 and 4, • D iscard any unused portion of the infusion solution. followed by every 8 weeks). 2 TREMFYA® (guselkumab) TREMFYA® (guselkumab) Weeks 0 to 16: to 1.1% of subjects in the placebo group. Neutrophil count decreased occurred in In the 16-week placebo-controlled period of the pooled clinical trials (PsO1 0.3% of subjects in the TREMFYA q8w and 1.6% of subjects in the TREMFYA q4w and PsO2), adverse events occurred in 49% of subjects in the TREMFYA group group compared to 0% of subjects in the placebo group. The majority of events of compared to 47% of subjects in the placebo group and 49% of subjects in the U.S. neutrophil count decreased were mild, transient, not associated with infection and licensed adalimumab group. Serious adverse events occurred in 1.9% of subjects did not lead to discontinuation. in the TREMFYA group (6.3 events per 100 subject-years of follow-up) compared to Ulcerative Colitis 1.4% of subjects in the placebo group (4.7 events per 100 subject-years of follow- TREMFYA was studied up to 12 weeks in subjects with moderately to severely active up), and in 2.6% of subjects in U.S. licensed adalimumab group (9.9 events per ulcerative colitis in a randomized, double-blind, placebo-controlled induction 100 subject-years of follow-up). study (UC1) and a randomized, double-blind, placebo controlled, induction dose- Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% finding study (UC3; NCT04033445). Long-term safety up to 44 weeks was evaluated and at a higher rate in the TREMFYA group than in the placebo group during the in subjects who responded to induction therapy in a randomized, double-blind, 16-week placebo-controlled period. placebo-controlled maintenance study (UC2) [see Clinical Studies (14.3)]. Table 1: Adverse Reactions Occurring in ≥1% of Subjects through Week 16 in PsO1 In the induction studies (UC1 and UC3), 522 subjects received at least one dose of and PsO2 the TREMFYA intravenous induction regimen (i.e., 200 mg at Week 0, Week 4, and Week 8). Clinical response was defined as a decrease in modified Mayo score TREMFYAa (mMS) of ≥30% and ≥2 points from baseline with either a ≥1 decrease from baseline 100 mg Adalimumabb Placebo N=823 N=196 N=422 in rectal bleeding subscore (RBS) or RBS of 0 or 1. In the maintenance study (UC2), n (%) n (%) n (%) subjects who achieved clinical response after 12 weeks of TREMFYA intravenous induction treatment were randomized and received either TREMFYA 100 mg every Upper respiratory infectionsc 118 (14.3) 21 (10.7) 54 (12.8) 8 weeks (with the first dose given at Week 4 of UC2) or TREMFYA 200 mg every Headached 38 (4.6) 2 (1.0) 14 (3.3) 4 weeks (with the first dose given at Week 0 of UC2), by subcutaneous (SC) injection for up to an additional 44 weeks. Injection site reactionse 37 (4.5) 15 (7.7) 12 (2.8) Respiratory tract infections occurred in ≥2% of subjects treated with TREMFYA Arthralgia 22 (2.7) 4 (2.0) 9 (2.1) and at a higher rate than placebo (8.8% TREMFYA-treated subjects vs. 7.3% Diarrhea 13 (1.6) 3 (1.5) 4 (0.9) placebo-treated subjects) through Week 12 in the induction studies (UC1 and UC3). Respiratory tract infections included COVID-19, influenza, nasopharyngitis, Gastroenteritisf 11 (1.3) 4 (2.0) 4 (0.9) respiratory tract infection, upper respiratory tract infection, and viral respiratory Tinea infectionsg 9 (1.1) 0 0 tract infection. Herpes simplex infectionsh 9 (1.1) 0 2 (0.5) Adverse reactions that occurred in ≥3% of subjects treated with TREMFYA and at a higher rate than placebo through Week 44 in the maintenance study (UC2) are a S ubjects receiving 100 mg of TREMFYA at Week 0, Week 4, and every 8 weeks shown in Table 2. thereafter b U.S. licensed adalimumab Table 2: Adverse Reactions Occurring in ≥3% of Subjects through Week 44 in UC2 c Upper respiratory infections include nasopharyngitis, upper respiratory tract TREMFYAa TREMFYAa infection (URTI), pharyngitis, and viral URTI. 100 mg 200 mg d Headache includes headache and tension headache. e Subcutaneous Subcutaneous Injection site reactions include injection site erythema, bruising, hematoma, Injection Injection Placebo hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria. N=186 N=190 N=192 f Gastroenteritis includes gastroenteritis and viral gastroenteritis. n (%) n (%) n (%) g T inea infections include tinea pedis, tinea cruris, tinea infection, and tinea Injection site reactionsb 2 (1.1) 17 (8.9)c 2 (1) manuum infections. h Herpes simplex infections include oral herpes, herpes simplex, genital herpes, Arthralgia 8 (4.3) 15 (7.9) 13 (6.8) genital herpes simplex, and nasal herpes simplex. Upper respiratory Adverse reactions that occurred in < 1% but > 0.1% of subjects in the TREMFYA tract infection 6 (3.2) 13 (6.8) 8 (4.2) group and at a higher rate than in the placebo group through Week 16 in PsO1 and a Subjects receiving TREMFYA 100 mg at Week 16 and every 8 weeks thereafter or PsO2 were migraine, candida infections, and urticaria. TREMFYA 200 mg at Week 12 and every 4 weeks thereafter. Specific Adverse Reactions b Injection site reactions include administration site pain, injection site hematoma, Infections injection site hemorrhage, injection site hypersensitivity, injection site erythema, Infections occurred in 23% of subjects in the TREMFYA group compared to 21% of injection site pain, injection site pruritus, injection site rash, injection site reaction, subjects in the placebo group. and injection site urticaria. c The most common (≥ 1%) infections were upper respiratory infections, TREMFYA 200 mg was administered as two 100 mg injections. gastroenteritis, tinea infections, and herpes simplex infections; all cases were mild 6.2 Postmarketing Experience to moderate in severity and did not lead to discontinuation of TREMFYA. The following adverse reactions have been reported during post-approval of Elevated Liver Enzymes TREMFYA. Because these reactions are reported voluntarily from a population Elevated liver enzymes were reported more frequently in the TREMFYA group of uncertain size, it is not always possible to reliably estimate their frequency or (2.6%) than in the placebo group (1.9%). Of the 21 subjects who were reported establish a causal relationship to TREMFYA exposure. to have elevated liver enzymes in the TREMFYA group, all events except one Immune system disorders: Hypersensitivity, including anaphylaxis [see Warnings were mild to moderate in severity and none of the events led to discontinuation and Precautions (5.1)] of TREMFYA. Skin and subcutaneous tissue disorders: Rash [see Warnings and Precautions (5.1)] Safety through Week 48 7 DRUG INTERACTIONS Through Week 48, no new adverse reactions were identified with TREMFYA 7.1 CYP450 Substrates use and the frequency of the adverse reactions was similar to the safety profile The formation of CYP450 enzymes can be altered by increased levels of certain observed during the first 16 weeks of treatment. cytokines (e.g., IL-1, IL-6, IL-10, TNFα, interferon) during chronic inflammation. Psoriatic Arthritis Results from an exploratory drug-drug interaction study in subjects with moderate- TREMFYA was studied in two placebo-controlled trials in subjects with psoriatic to-severe plaque psoriasis suggested a low potential for clinically relevant drug arthritis (748  subjects on TREMFYA and 372  subjects on placebo). Of the interactions for drugs metabolized by CYP3A4, CYP2C9, CYP2C19 and CYP1A2 but 748  subjects who received TREMFYA, 375  subjects received TREMFYA  100  mg the interaction potential cannot be ruled out for drugs metabolized by CYP2D6. at Week  0, Week  4, and every 8  weeks thereafter and 373  subjects received However, the results were highly variable because of the limited number of TREMFYA 100 mg every 4 weeks. The overall safety profile observed in subjects subjects in the study. with psoriatic arthritis treated with TREMFYA is generally consistent with the Upon initiation of TREMFYA in patients who are receiving concomitant CYP450 safety profile in subjects with plaque psoriasis with the addition of bronchitis substrates, particularly those with a narrow therapeutic index, consider monitoring and neutrophil count decreased. In the 24-week placebo-controlled period, for therapeutic effect or drug concentration and consider dosage adjustment as combined across the two studies, bronchitis occurred in 1.6% of subjects in the needed [see Clinical Pharmacology (12.3)]. TREMFYA q8w group and 2.9% of subjects in the TREMFYA q4w group compared 3 TREMFYA® (guselkumab) TREMFYA® (guselkumab) 8 USE IN SPECIFIC POPULATIONS 11 DESCRIPTION 8.1 Pregnancy Guselkumab, an interleukin-23 antagonist, is a human immunoglobulin G1 lambda Pregnancy Exposure Registry (IgG1λ) monoclonal antibody. Guselkumab is produced in a mammalian cell line There is a pregnancy registry that monitors pregnancy outcomes in women using recombinant DNA technology and has an approximate molecular weight of exposed to TREMFYA during pregnancy. Patients should be encouraged approximately 147 kDa. to enroll in the registry by visiting www.mothertobaby.org/ongoing-study/ TREMFYA® (guselkumab) injection is a sterile, preservative free, clear, and tremfya-guselkumab, by calling 1-877-311-8972, or emailing MotherToBaby@ colorless to light yellow solution. health.ucsd.edu. TREMFYA for Subcutaneous Injection Risk Summary Available as a 100 mg/mL solution in a 1 mL or 2 mL glass prefilled syringe, in a 2 mL Available data from literature, post-marketing reports, and ongoing pregnancy prefilled pen, or in a 1 mL One-Press patient-controlled injector for subcutaneous use. registry with TREMFYA use in pregnant women are insufficient to establish a drug- Each TREMFYA 1 mL prefilled syringe or One-Press patient-controlled injector associated risk of major birth defects, miscarriage or other adverse maternal or delivers 100 mg guselkumab, L-histidine (0.6 mg), L-histidine monohydrochloride fetal outcomes. Human IgG antibodies are known to cross the placental barrier; monohydrate (1.5 mg), polysorbate 80 (0.5 mg), sucrose (79 mg) and water for therefore, TREMFYA may be transmitted from the mother to the developing fetus. injection at pH 5.8. In a combined embryofetal development and pre- and post-natal development Each TREMFYA 2 mL prefilled syringe or prefilled pen (TREMFYA PEN) delivers 200 mg study, no adverse developmental effects were observed in infants born to guselkumab, L-histidine (1.2 mg), L-histidine monohydrochloride monohydrate pregnant monkeys after subcutaneous administration of guselkumab during (3 mg), polysorbate 80 (1 mg), sucrose (158 mg) and water for injection at pH 5.8. organogenesis through parturition at doses up to 18 times the exposure (AUC) in TREMFYA for Intravenous Infusion humans administered 200 mg intravenously and 32 times the exposure (AUC) to the Available as 10 mg/mL solution in a 20 mL single-dose vial for intravenous use. 200 mg dose given subcutaneously. Neonatal deaths in monkeys were observed at 4 to 18 times the exposure (AUC) in humans administered 200 mg intravenously Each TREMFYA 20 mL vial delivers 200 mg guselkumab, EDTA disodium dihydrate and 7 to 32 times the exposure (AUC) to the 200 mg dose given subcutaneously (see (0.4 mg), L-histidine (11.3 mg), L-histidine monohydrochloride monohydrate Data). The clinical significance of these nonclinical findings is unknown. (26.6  mg), L-methionine (8 mg), polysorbate 80 (10 mg), sucrose (1700 mg) and water for injection at pH 5.8. 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 12 CLINICAL PHARMACOLOGY indicated population is unknown. In the U.S. general population, the estimated 12.1 Mechanism of Action background risk of major birth defects and miscarriage in clinically recognized Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 pregnancies is 2% to 4% and 15% to 20%, respectively. subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and Clinical Considerations immune responses. Guselkumab inhibits the release of proinflammatory cytokines Disease-Associated Maternal and Embryo/Fetal Risk and chemokines. Published data suggest that the risk of adverse pregnancy outcomes in women 12.2 Pharmacodynamics with inflammatory bowel disease (IBD) is associated with increased disease In evaluated subjects with plaque psoriasis, guselkumab reduced serum levels activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of IL-17A, IL-17F and IL-22 relative to pre-treatment levels based on exploratory gestation), low birth weight (less than 2500 g) infants, and small for gestational analyses of the pharmacodynamic markers. age at birth. In evaluated subjects with psoriatic arthritis, serum levels of acute phase proteins Data C-reactive protein, serum amyloid A and IL-6, and Th17 effector cytokines Animal Data IL-17A, IL-17F and IL-22 were elevated at baseline. Serum levels of these proteins In a combined embryofetal development and pre- and post-natal development measured at Week 4 and Week 24 were decreased compared to baseline following study, pregnant cynomolgus monkeys were administered weekly subcutaneous guselkumab treatment at Week 0, Week 4 and every 8 weeks thereafter. doses of guselkumab from the beginning of organogenesis to parturition at a The relationship between these pharmacodynamic markers and the mechanism(s) dose (50 mg/kg) resulting in exposures (AUC) 18 times the exposure in humans by which guselkumab exerts its clinical effects is unknown. administered 200 mg intravenously and 32 times the human exposure at 200 mg 12.3 Pharmacokinetics given subcutaneously. Neonatal deaths occurred in the offspring of one control Guselkumab exhibited linear pharmacokinetics in healthy subjects and subjects monkey, three monkeys administered guselkumab at 10 mg/kg/week (4 times the with plaque psoriasis following subcutaneous injections. In subjects with plaque exposure (AUC) in humans administered 200 mg intravenously and 7 times the psoriasis, following subcutaneous administration of 100 mg of TREMFYA at Weeks 0 exposure (AUC) at 200 mg given subcutaneously) and three monkeys administered and 4, and every 8 weeks thereafter, mean steady-state trough serum guselkumab guselkumab at 50 mg/kg/week (18 times the exposure (AUC) in humans concentration was approximately 1.2 mcg/mL. administered 200 mg intravenously and 32 times the exposure (AUC) following a The pharmacokinetics of guselkumab in subjects with psoriatic arthritis was similar 200 mg subcutaneous dose). The clinical significance of these findings is unknown. to that in subjects with plaque psoriasis. Following subcutaneous administration of No guselkumab-related effects on functional or immunological development were 100 mg of TREMFYA at Weeks 0, 4, and every 8 weeks thereafter, mean steady- observed in the infants from birth through 6 months of age. state trough serum guselkumab concentration was approximately 1.2 mcg/mL. 8.2 Lactation Following subcutaneous maintenance dosing of 100 mg TREMFYA every 8 weeks Risk Summary or 200 mg TREMFYA every 4 weeks in subjects with ulcerative colitis, mean steady- There are no data on the presence of guselkumab in human milk, the effects state trough serum guselkumab concentrations were approximately 1.4 mcg/mL on the breastfed infant, or the effects on milk production. Guselkumab was not and 10.7 mcg/mL, respectively. detected in the milk of lactating cynomolgus monkeys. Endogenous maternal IgG Absorption and monoclonal antibodies are transferred into human milk. The effects of local Following a single 100 mg subcutaneous injection in healthy subjects, guselkumab gastrointestinal exposure and the extent of systemic exposure in the breastfed reached a mean (± SD) maximum serum concentration of 8.09 ± 3.68 mcg/mL by infant to guselkumab are unknown. The developmental and health benefits of approximately 5.5 days post dose. The absolute bioavailability of guselkumab breastfeeding should be considered along with the mother's clinical need for following a single 100 mg subcutaneous injection was estimated to be TREMFYA and any potential adverse effects on the breastfed infant from TREMFYA approximately 49% in healthy subjects. or from the underlying maternal condition. Following the recommended intravenous induction dose regimen of TREMFYA 8.4 Pediatric Use 200 mg at Weeks 0, 4, and 8, mean (± SD) peak serum guselkumab concentration at The safety and efficacy of TREMFYA in pediatric patients (less than 18 years of Week 8 was 68.3 ± 17.3 mcg/mL in subjects with ulcerative colitis. age) have not been established. Distribution 8.5 Geriatric Use In subjects with plaque psoriasis, apparent volume of distribution was 13.5 L. In subjects with ulcerative colitis, apparent volume of distribution at steady-state Of the 4303 subjects with plaque psoriasis, psoriatic arthritis, or ulcerative colitis was 10.1 L. exposed to TREMFYA, a total of 240 subjects were 65 years or older, and 23 subjects were 75 years or older. Clinical studies of TREMFYA, within each indication, did Elimination not include sufficient numbers of subjects 65 years of age and older to determine Apparent clearance in subjects with plaque psoriasis was 0.516 L/day. Mean whether they respond differently from younger adult subjects. half-life of guselkumab was approximately 15 to 18 days in subjects with plaque psoriasis across trials. No clinically meaningful differences in the pharmacokinetics of guselkumab were observed based on age [see Clinical Pharmacology (12.3)]. The apparent clearance in subjects with ulcerative colitis was 0.531 L/day. Mean half-life of guselkumab was approximately 17 days in subjects with ulcerative colitis. 4 TREMFYA® (guselkumab) TREMFYA® (guselkumab) Metabolism 18 years of age and older with moderate-to-severe plaque psoriasis who were The exact pathway through which guselkumab is metabolized has not been eligible for systemic therapy or phototherapy. Subjects had an Investigator’s Global characterized. As a human IgG monoclonal antibody, guselkumab is expected to Assessment (IGA) score of ≥3 (“moderate”) on a 5-point scale of overall disease be degraded into small peptides and amino acids via catabolic pathways in the severity, a Psoriasis Area and Severity Index (PASI) score ≥12, and a minimum same manner as endogenous IgG. affected body surface area (BSA) of 10%. Subjects with guttate, erythrodermic, or Specific Populations pustular psoriasis were excluded. No apparent differences in clearance were observed in subjects ≥ 65 years of Trials PsO1 and PsO2 age compared to subjects < 65 years of age, suggesting no dose adjustment is In PsO1 and PsO2, 1443 subjects were randomized to either TREMFYA (100 mg at needed for elderly subjects. Clearance and volume of distribution of guselkumab Weeks 0 and 4 and every 8 weeks thereafter) administered with a prefilled syringe, increases as body weight increases, however, observed clinical trial data indicate placebo or U.S. licensed adalimumab (80 mg at Week 0 and 40 mg at Week 1, that dose adjustment for body weight is not warranted. No specific trials have followed by 40 mg every other week thereafter). been conducted to determine the effect of renal or hepatic impairment on the Both trials assessed the responses at Week 16 compared to placebo for the two pharmacokinetics of guselkumab. co-primary endpoints: Drug Interactions • the proportion of subjects who achieved an IGA score of 0 (“cleared”) or 1 Population pharmacokinetic analyses indicated that concomitant use of NSAIDs, oral (“minimal”); corticosteroids and conventional DMARDs such as methotrexate (MTX), azathioprine • the proportion of subjects who achieved at least a 90% reduction from baseline (AZA), and 6-mercaptopurine (6-MP), did not affect the clearance of guselkumab. in the PASI composite score (PASI 90). Cytochrome P450 Substrates Comparisons between TREMFYA and U.S. licensed adalimumab were secondary The effects of guselkumab on the pharmacokinetics of midazolam (metabolized endpoints at the following time points: by CYP3A4), warfarin (metabolized by CYP2C9), omeprazole (metabolized by • at Week 16 (PsO1 and PsO2), the proportions of subjects who achieved an IGA CYP2C19), dextromethorphan (metabolized by CYP2D6), and caffeine (metabolized score of 0 or 1, a PASI 90, and a PASI 75 response; by CYP1A2) were evaluated in an exploratory study with 6 to 12 evaluable subjects with moderate-to-severe plaque psoriasis. Changes in AUC • at Week 24 (PsO1 and PsO2), and at Week 48 (PsO1), the proportions of subjects inf of midazolam, S-warfarin, omeprazole, and caffeine after a single dose of guselkumab were not achieving an IGA score of 0, an IGA score of 0 or 1, and a PASI 90 response. clinically relevant. For dextromethorphan, changes in AUCinf after guselkumab Other evaluated outcomes included improvement in psoriasis symptoms assessed were not clinically relevant in 9 out of 10 subjects; however, a 2.9-fold change in on the Psoriasis Symptoms and Signs Diary (PSSD) and improvements in psoriasis AUCinf was observed in one individual [see Drug Interactions (7.1)]. of the scalp at Week 16. 12.6 Immunogenicity In both trials, subjects were predominantly men and white, with a mean age of The observed incidence of anti-drug antibodies is highly dependent on the 44 years and a mean weight of 90 kg. At baseline, subjects had a median affected sensitivity and specificity of the assay. Differences in assay methods preclude BSA of approximately 21%, a median PASI score of 19, and 18% had a history of meaningful comparisons of the incidence of anti-drug antibodies in the studies psoriatic arthritis. Approximately 24% of subjects had an IGA score of severe. In described below with the incidence of anti-drug antibodies in other studies, both trials, 23% had received prior biologic systemic therapy. including those of guselkumab or of other guselkumab products. Clinical Response Plaque Psoriasis Table 3 presents the efficacy results at Week 16 in PsO1 and PsO2. Up to Week 52, approximately 6% of subjects treated with TREMFYA developed Table 3: Efficacy Results at Week 16 in Adults with Plaque Psoriasis (NRIa) antidrug antibodies. Of the subjects who developed antidrug antibodies, approximately 7% had antibodies that were classified as neutralizing antibodies. PsO1 PsO2 Among the 46 subjects who developed antibodies to guselkumab and had evaluable TREMFYA Placebo TREMFYA Placebo data, 21 subjects exhibited lower trough levels of guselkumab, including one subjects (N=329) (N=174) (N=496) (N=248) who experienced loss of efficacy after developing high antibody titers. Up to Week Endpoint n (%) n (%) n (%) n (%) 156, approximately 9% of subjects treated with TREMFYA developed antidrug antibodies and of these subjects approximately 6% were classified as neutralizing IGA response of 0/1b,c 280 (85) 12 (7) 417 (84) 21 (8) antibodies. However, antibodies to guselkumab were generally not associated with PASI 90 responseb 241 (73) 5 (3) 347 (70) 6 (2) changes in clinical response or development of injection-site reactions. a NRI = Non-Responder Imputation Psoriatic Arthritis b Co-Primary Endpoints Up to Week 24, 2% (n=15) of subjects treated with TREMFYA developed antidrug c IGA response of 0 (cleared) or 1 (minimal) antibodies. Of these subjects, 1 had antibodies that were classified as neutralizing antibodies. Overall, the small number of subjects who were positive for antibodies Table 4 presents the results of an analysis of all the North America sites (i.e., U.S. to guselkumab limits definitive conclusion of the effect of immunogenicity on the and Canada), demonstrating superiority of TREMFYA to U.S. licensed adalimumab. pharmacokinetics, efficacy and safety of guselkumab. Table 4: Efficacy Results in Adults with Plaque Psoriasis (NRIa) Ulcerative Colitis PsO1 PsO2 Up to Week 56 in Studies UC1, UC2 and UC3, 11% (n=48) of subjects treated with TREMFYA at the recommended dosage developed antidrug antibodies. Of these TREMFYA Adalimumabc TREMFYA Adalimumabc (N=115)b (N=115)b (N=160)b (N=81)b subjects who tested positive for anti-guselkumab antibodies and were evaluable for neutralizing antibodies, 16% (n=6) had antibodies that were classified as Endpoint n (%) n (%) n (%) n (%) neutralizing antibodies. Most of the subjects who were positive for antibodies to IGA response of 0/1 (cleared or minimal) guselkumab had low titers. Two subjects with the highest antibody titers exhibited low trough levels of guselkumab. There was no identified clinically significant Week 16 97 (84) 70 (61) 119 (74) 50 (62) effect of antidrug antibodies on injection site reactions, or effectiveness of Week 24 97 (84) 62 (54) 119 (74) 46 (57) guselkumab, over the treatment duration of 56 weeks. Week 48 91 (79) 62 (54) NA NA 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility IGA response of 0 (cleared) Animal studies have not been conducted to evaluate the carcinogenic or Week 24 61 (53) 27 (23) 76 (48) 23 (28) mutagenic potential of TREMFYA. Week 48 54 (47) 28 (24) NA NA No effects on fertility parameters were observed after male guinea pigs were subcutaneously administered guselkumab at a dose of 25 mg/kg twice weekly PASI 75 response (6 times the exposure (AUC) in humans administered 200 mg intravenously and Week 16 105 (91) 80 (70) 132 (83) 51 (63) 10 times the exposure (AUC) at the 200 mg subcutaneous dose). No effects on fertility parameters were observed after female guinea pigs were PASI 90 response subcutaneously administered guselkumab at doses up to 100 mg/kg twice weekly Week 16 84 (73) 47 (41) 102 (64) 34 (42) (12 times the exposure (AUC) in humans administered 200 mg intravenously and 21 times the exposure (AUC) at the 200 mg subcutaneous dose). Week 24 92 (80) 51 (44) 113 (71) 41 (51) 14 CLINICAL STUDIES Week 48 84 (73) 53 (46) NA NA 14.1 Plaque Psoriasis a NRI = Non-Responder Imputation Four multicenter, randomized, double-blind trials (PsO1 [NCT02207231], PsO2 b Subjects from sites in the United States and Canada [NCT02207244], PsO3 [NCT02203032], and PsO4 [NCT02905331]) enrolled subjects c U.S. licensed adalimumab 5 TREMFYA® (guselkumab) TREMFYA® (guselkumab) An improvement was seen in psoriasis involving the scalp in subjects randomized Clinical Response to TREMFYA compared to placebo at Week 16. In both trials, subjects treated with TREMFYA 100 mg q8w demonstrated a greater Examination of age, gender, race, body weight, and previous treatment with clinical response including ACR20, compared to placebo at Week 24 (Tables 5 and 6). systemic or biologic agents did not identify differences in response to TREMFYA Similar responses were seen regardless of prior anti-TNFα exposure in PsA1, and among these subgroups. in both trials similar responses were seen regardless of concomitant cDMARD use, previous treatment with cDMARDs, gender and body weight. Maintenance and Durability of Response To evaluate maintenance and durability of response (PsO2), subjects randomized Table 5: Percent of Subjects with ACR Responses in PsA1 to TREMFYA at Week 0 and who were PASI 90 responders at Week 28 were Placebo TREMFYA re-randomized to either continue treatment with TREMFYA every 8 weeks or be (N=126) 100 mg q8w withdrawn from therapy (i.e., receive placebo). (N=127) At Week 48, 89% of subjects who continued on TREMFYA maintained PASI 90 Response Response Difference from Placebo compared to 37% of subjects who were re-randomized to placebo and withdrawn Rate Rate (95% CI) from TREMFYA. For responders at Week 28 who were re-randomized to placebo and withdrawn from TREMFYA, the median time to loss of PASI 90 was approximately ACR 20 responsea 15 weeks. Week 16 25% 52% 27 (15, 38) Patient Reported Outcomes Week 24 22% 52% 30 (19, 41) Greater improvements in symptoms of psoriasis (itch, pain, stinging, burning and ACR 50 responsea skin tightness) at Week 16 in TREMFYA compared to placebo were observed in both trials based on the Psoriasis Symptoms and Signs Diary (PSSD). Greater Week 16 13% 23% 10 (1, 19) proportions of subjects on TREMFYA compared to U.S. licensed adalimumab Week 24 9% 30% 21 (12, 31) achieved a PSSD symptom score of 0 (symptom-free) at Week 24 in both trials. ACR 70 responsea Trial PsO3 Week 16 6% 8% 2 (-4, 8) PsO3 [NCT02203032] evaluated the efficacy of 24 weeks of treatment with TREMFYA in subjects (N=268) who had not achieved an adequate response, defined as IGA Week 24 6% 12% 6 (-0.3, 13) ≥2 at Week 16 after initial treatment with U.S. licensed ustekinumab (dosed 45 mg a Subjects with missing data at a visit were imputed as non-responders at that or 90 mg according to the subject’s baseline weight at Week 0 and Week 4). These visit. Subjects who met escape criteria (less than 5% improvement in both tender subjects were randomized to either continue with U.S. licensed ustekinumab and swollen joint counts) at Week 16 were allowed to initiate or increase the treatment every 12 weeks or switch to TREMFYA 100 mg at Weeks 16, 20, and every dose of the permitted concomitant medication and remained on the randomized 8 weeks thereafter. Baseline characteristics for randomized subjects were similar group. Subjects who initiated or increased the dose of non-biologic DMARD to those observed in PsO1 and PsO2. or oral corticosteroids over baseline, discontinued study/study medication or In subjects with an inadequate response (IGA ≥2 at Week 16 to U.S. licensed initiated protocol prohibited medications/therapies for PsA prior to a visit were ustekinumab), greater proportions of subjects on TREMFYA compared to U.S. considered non-responders at that visit. licensed ustekinumab achieved an IGA score of 0 or 1 with a ≥2 grade improvement Table 6: Percent of Subjects with ACR Responses in PsA2 at Week 28 (31% vs. 14%, respectively; 12 weeks after randomization). Placebo TREMFYA Trial PsO4 (N=246) 100 mg q8w PsO4 [NCT02905331] evaluated the efficacy, safety, and pharmacokinetics of (N=248) TREMFYA administered with the One-Press injector. In this study, 78 subjects Response Response Difference from Placebo were randomized to receive either TREMFYA (100 mg at Weeks 0 and 4 and Rate Rate (95% CI) every 8 weeks thereafter) [N=62], or placebo [N=16]. Baseline characteristics for subjects were comparable to those observed in PsO1 and PsO2. The co-primary ACR 20 responsea endpoints were the same as those for PsO1 and PsO2. Secondary endpoints Week 16 34% 55% 22 (13, 30) included the proportion of subjects who achieved an IGA score of 0 at Week 16 and the proportion of subjects who achieved a PASI 100 response at Week 16. Week 24 33% 64% 31 (23, 40) A greater proportion of subjects in the guselkumab group achieved an IGA score ACR 50 responsea of 0 or 1 or a PASI 90 response at Week 16 (81% and 76%, respectively) than in the Week 16 9% 29% 19 (13, 26) placebo group (0% for both endpoints). The proportion of subjects who achieved an IGA score of 0 at Week 16 was higher in the guselkumab group compared to Week 24 14% 32% 17 (10, 24) the placebo group (56% vs. 0%). The proportion of subjects who achieved a PASI ACR 70 responsea 100 response at Week 16 was higher in the guselkumab group compared to the Week 16 1% 14% 13 (9, 17) placebo group (50% vs. 0%). Week 24 4% 19% 15 (9, 20) 14.2 Psoriatic Arthritis a The safety and efficacy of TREMFYA were assessed in 1120 subjects in 2 Subjects with missing data at a visit were imputed as non-responders at that randomized, double-blind, placebo-controlled trials (PsA1 [NCT03162796] and PsA2 visit. Subjects who met escape criteria (less than 5% improvement in both tender [NCT03158285]) in adult subjects with active psoriatic arthritis (PsA) (≥3 swollen and swollen joint counts) at Week 16 were allowed to initiate or increase the joints, ≥3 tender joints, and a C-reactive protein (CRP) level of ≥0.3 mg/dL in PsA1 dose of the permitted concomitant medication and remained on the randomized and ≥5 swollen joints, ≥5 tender joints, and a CRP level of ≥0.6 mg/dL in PsA2) group. Subjects who initiated or increased the dose of non-biologic DMARD who had inadequate response to standard therapies (e.g., conventional DMARDs or oral corticosteroids over baseline, discontinued study/study medication or [cDMARDs]), apremilast, or nonsteroidal anti-inflammatory drugs [NSAIDs]). initiated protocol prohibited medications/therapies for PsA prior to a visit were Subjects in these trials had a diagnosis of PsA for at least 6 months based on the considered non-responders at that visit. Classification criteria for Psoriatic Arthritis (CASPAR) and a median duration of The percentage of subjects achieving ACR20 response in PsA2 by visit is shown PsA of 4 years at baseline. in Figure 1. In PsA1 approximately 31% of subjects had been previously treated with up Figure 1: Subjects Achieving ACR 20 Response by Visit Through Week 24 in PsA2 to 2 anti-tumor necrosis factor alpha (anti-TNFα) agents whereas in PsA2 all 100 subjects were biologic naïve. Approximately 58% of subjects from both trials had concomitant methotrexate (MTX) use. Subjects with different subtypes of PsA were enrolled in both trials, including polyarticular arthritis with the absence of 80 rheumatoid nodules (40%), spondylitis with peripheral arthritis (30%), asymmetric peripheral arthritis (23%), distal interphalangeal involvement (7%) and arthritis mutilans (1%). At baseline, over 65% and 42% of the subjects had enthesitis and dactylitis, respectively and 79% had ≥3% body surface area (BSA) psoriasis skin involvement. 40 PsA1 evaluated 381 subjects who were treated with placebo SC, TREMFYA 100 mg SC at Weeks 0, 4 and every 8 weeks (q8w) thereafter, or TREMFYA 100 mg SC every 20 4 weeks (q4w). PsA2 evaluated 739 subjects who were treated with placebo SC, TREMFYA 100 mg SC at Weeks 0, 4 and q8w thereafter, or TREMFYA 100 mg SC q4w. The primary endpoint in both trials was the percentage of subjects achieving an ACR20 response at Week 24. 12 16 20 24 Weeks ---@--- Placebo (n=246) Guselkumab 100 mg (n=248) 6 Percent of Subjects (%) TREMFYA® (guselkumab) TREMFYA® (guselkumab) The results of the components of the ACR response criteria are shown in Table 7. Treatment with TREMFYA resulted in an improvement in the skin manifestations of psoriasis in subjects with PsA. Table 7: Mean change (SDa) from Baseline in ACR Component Scores at Treatment with TREMFYA resulted in improvement in dactylitis and enthesitis in Week 16 and 24 based on Observed Data subjects with pre-existing dactylitis or enthesitis. PsA1 PsA2 Physical Function Placebo TREMFYA Placebo TREMFYA TREMFYA treated subjects in the TREMFYA 100 mg q8w group in both PsA1 and (N=126) 100 mg N=246 100 mg PsA2 showed greater mean improvement from baseline in physical function q8w q8w compared to subjects treated with placebo as assessed by the Health Assessment (N=127) (N=248) Questionnaire-Disability Index (HAQ-DI) at Weeks 16 and 24. In both studies, the proportion of HAQ-DI responders (≥0.35 improvement in HAQ-DI score) was No. of Swollen Joints greater in the TREMFYA q8w dose group compared to placebo at Weeks 16 and 24. Baseline 10.1 (7.1) 10.9 (9.3) 12.3 (6.9) 11.7 (6.8) Other Health-Related Outcomes Mean change at -4.2 (7.0) -7.3 (7.0) -5.8 (7.1) -7.2 (6.0) General health status was assessed by the Short Form health survey (SF-36). At Week 16 Week 24, subjects in the TREMFYA 100 mg q8w dose group in both PsA1 and PsA2 showed greater improvement from baseline in the SF-36 physical component Mean change at -5.1 (6.9) -7.3 (8.0) -6.4 (7.2) -8.1 (6.1) summary (PCS) compared with placebo. There was not a statistically significant Week 24 improvement observed in the SF-36 MCS. At Week 24, there was numerical improvement in the physical functioning, role-physical, bodily-pain, general health, No. of Tender Joints social-functioning and vitality domains but not in the role-emotional and mental Baseline 19.8 (14.4) 20.2 (14.5) 21.6 (13.1) 19.8 (11.9) health domains. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue score (FACIT-F) in Studies PsA1 and PsA2. Treatment with Mean change at -4.5 (10.8) -10.2 (10.4) -6.8 (10.5) -9.0 (9.4) TREMFYA resulted in improvement in fatigue as measured by FACIT-F. Week 16 14.3 Ulcerative Colitis Mean change at -6.8 (13.0) -10.5 (12.0) -7.3 (11.2) -10.4 (9.5) Induction Trial: UC1 Week 24 In the 12-week induction study (UC1; NCT04033445), 701 subjects with moderately Patient’s Assessment of Painb to severely active ulcerative colitis were randomized 3:2 to receive either TREMFYA 200 mg or placebo by intravenous infusion at Week 0, Week 4, and Week 8. Disease Baseline 5.8 (2.2) 6.0 (2.1) 6.3 (1.8) 6.3 (2.0) activity was assessed by the modified Mayo score (mMS), a 3-component Mayo score (0-9) which consists of the following subscores (0 to 3 for each subscore): Mean change at -0.8 (2.3) -1.7 (2.4) -0.9 (2.3) -2.2 (2.5) stool frequency (SFS), rectal bleeding (RBS), and findings on centrally reviewed Week 16 endoscopy (ES). An ES of 2 was defined by marked erythema, lack of vascular Mean change at -0.7 (2.4) -2.2 (2.6) -1.1 (2.4) -2.5 (2.5) pattern, friability, and/or erosions; an ES of 3 was defined by spontaneous bleeding Week 24 and ulceration. Enrolled subjects with a mMS between 5 and 9 and an ES of 2 or 3 were classified as having moderately to severely active ulcerative colitis. Subjects Patient Global Assessmentb with inadequate response, loss of response, or intolerance to corticosteroids, Baseline 6.1 (2.2) 6.5 (2.0) 6.5 (1.8) 6.5 (1.9) immunomodulators (azathioprine, 6-mercaptopurine), biologic therapy (TNF blockers, vedolizumab), and/or Janus kinase (JAK) inhibitors were enrolled. Mean change at -1.0 (2.3) -2.0 (2.6) -1.0 (2.3) -2.3 (2.6) At baseline in UC1, the median mMS was 7, 64% of subjects had severely active Week 16 disease (mMS ≥7), and 68% of subjects had an ES of 3. In UC1, 49% of subjects had Mean change at -0.9 (2.5) -2.5 (2.7) -1.2 (2.6) -2.5 (2.5) previously failed (inadequate response, loss of response, or intolerance) treatment Week 24 with at least one biologic therapy and/or JAK inhibitor, 48% were biologic and JAK inhibitor naïve, and 3% had previously received but not failed a biologic or JAK Physician Global Assessmentb inhibitor. The median age was 39 years (ranging from 18 to 79 years); 43% were female; and 72% identified as White, 21% as Asian, 1% as Black or African American, Baseline 6.3 (1.7) 6.2 (1.7) 6.7 (1.5) 6.6 (1.6) <1% as American Indian or Alaskan Native, and <1% as multiple racial groups. Mean change at -1.9 (2.2) -2.9 (2.4) -2.1 (2.2) -3.5 (2.3) Enrolled subjects were permitted to use stable doses of oral aminosalicylates, Week 16 immunomodulators (azathioprine, 6-mercaptopurine, methotrexate), and/or oral Mean change at -2.2 (2.3) -3.5 (2.4) -2.5 (2.3) -3.8 (2.3) corticosteroids (up to 20 mg/day prednisone or equivalent). At baseline, 72% Week 24 of subjects were receiving aminosalicylates, 21% of subjects were receiving immunomodulators, and 43% of subjects were receiving corticosteroids. Disability Index (HAQ-DI)c Concomitant biologic therapies or JAK inhibitors were not permitted. Baseline 1.2 (0.7) 1.2 (0.6) 1.3 (0.6) 1.3 (0.6) In UC1, the primary endpoint was clinical remission at Week 12 as defined by the mMS. Secondary endpoints at Week 12 included endoscopic improvement, clinical Mean change at -0.1 (0.5) -0.3 (0.5) -0.1 (0.5) -0.3 (0.5) response, and histologic endoscopic mucosal improvement (see Table 8). Week 16 Table 8: Proportion of Subjects with Ulcerative Colitis Meeting Efficacy Endpoints Mean change at -0.1 (0.5) -0.3 (0.6) -0.2 (0.5) -0.4 (0.5) at Week 12 in UC1 Week 24 Endpoint Placebo TREMFYA 200 mg Treatment CRP (mg/dL) Intravenous Difference Infusiona (95% CI) Baseline 1.4 (1.9) 1.6 (2.4) 2.1 (2.7) 2.0 (2.4) Clinical remissionb Mean change at -0.2 (1.5) -0.6 (2.2) -0.6 (2.5) -1.0 (2.2) Week 16 Total Population N=280 N=421 15% 8% 23% (10%, 20%)c Mean change at -0.0 (2.8) -0.7 (2.1) -0.5 (2.5) -1.1 (2.2) Week 24 Prior biologic and/or JAK N=136 N=208 inhibitor failured 4% 13% a SD= standard deviation Without prior biologic or JAK N=144 N=213 b Assessment based on Visual Analog Scale (cm) with the left end indicating inhibitor failuree 12% 32% “no pain” (for patient’s assessment of pain), “very well” (for patient global assessment), or “no arthritis activity” (for physician global assessment) and Endoscopic improvementf the right end indicating “the worst possible pain” (for patient assessment of Total Population N=280 N=421 16% pain), “poor” (for patient global assessment), or “extremely active arthritis (for 11% 27% (10%, 21%)c physician global assessment). c Disability Index of the Health Assessment Questionnaire; 0 = no difficulty to Prior biologic and/or JAK N=136 N=208 3 = inability to perform, measures the patient’s ability to perform the following: inhibitor failured 5% 15% dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of Without prior biologic or JAK N=144 N=213 daily living inhibitor failuree 17% 38% 7 TREMFYA® (guselkumab) TREMFYA® (guselkumab) Table 8: Proportion of Subjects with Ulcerative Colitis Meeting Efficacy Endpoints Table 9: Proportion of Subjects with Ulcerative Colitis Meeting Efficacy Endpoints at Week 12 in UC1 (continued) at Week 44 in UC2 Endpoint Placebo TREMFYA 200 mg Treatment Endpoint Placebo TREMFYA TREMFYA Treatment Difference Intravenous Difference Infusiona 100 mg 200 mg vs Placebo (95% CI) Every 8 Weeks Every 4 Weeks (95% CI) Clinical responseg Subcutaneous Subcutaneous Injectiona Injectionb TREMFYA TREMFYA Total Population N=280 N=421 34% 100 mg 200 mg 28% 62% (27%, 41%)c Clinical remissionc Prior biologic and/or JAK N=136 N=208 inhibitor failured 20% 51% Total populationd N=190 N=188 N=190 25% 30% Without prior biologic or JAK N=144 N=213 19% 45% 50% (16%, (21%, 34%)e 38%)e inhibitor failuree 35% 71% Histologic endoscopic mucosal improvement (HEMI)h Prior biologic N=75 N=77 N=88 and/or JAK 8% 40% 40% Total Population N=280 N=421 16% inhibitor failuref 8% 24% (11%, 21%)c Without prior N=115 N=111 N=102 Prior biologic and/or JAK N=136 N=208 biologic or JAK 26% 49% 59% inhibitor failured 4% 13% inhibitor failureg Without prior biologic or JAK N=144 N=213 Corticosteroid-free clinical remissionh inhibitor failuree 10% 33% a T REMFYA 200 mg as an intravenous infusion at Week 0, Week 4, and Week 8 Total populationd N=190 N=188 N=190 26% 29% b A stool frequency subscore of 0 or 1 and not increased from baseline, a rectal 18% 45% 49% (17%, (20%, bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability 34%)e 38%)e c p <0.001, adjusted treatment difference (95% CI) based on Cochran-Mantel- Haenszel method (adjusted for stratification factors: biologic and/or JAK- Prior biologic N=75 N=77 N=88 inhibitor failure status and concomitant use of corticosteroids at baseline) and/or JAK 7% 40% 40% inhibitor failuref d Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) and/or a Janus kinase (JAK) inhibitor for Without prior N=115 N=111 N=102 ulcerative colitis biologic or JAK 26% 49% 57% e I ncludes subjects that were biologic and/or JAK inhibitor naïve and subjects with inhibitor failureg biologic and/or JAK inhibitor exposure who did not meet criteria for failure. Of these, 7 subjects in the placebo group and 11 subjects in the TREMFYA group Endoscopic improvementi were previously exposed to, but did not fail, a biologic or JAK inhibitor f A n endoscopy subscore of 0 or 1 with no friability Total populationd N=190 N=188 N=190 30% 31% g D ecrease from induction baseline in the modified Mayo score by ≥30% and 19% 49% 52% (21%, (22%, 38%)e 40%)e ≥2 points, with either a ≥1 point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1 Prior biologic N=75 N=77 N=88 h A n endoscopy subscore of 0 or 1 with no friability and Geboes score ≤3.1 and/or JAK 8% 45% 42% (indicating neutrophil infiltration in <5% of crypts, no crypt destruction, and no inhibitor failuref erosions, ulcerations, or granulation tissue) Without prior N=115 N=111 N=102 Study UC1 was not designed to evaluate the relationship of histologic endoscopic biologic or JAK 26% 52% 60% mucosal improvement at Week 12 to disease progression and long-term outcomes. inhibitor failureg Rectal Bleeding and Stool Frequency Subscores Histologic endoscopic mucosal improvement (HEMI)j Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 4 in subjects treated with TREMFYA compared to placebo. Total populationd N=190 N=188 N=190 26% 30% 17% 44% 48% (17%, (21%, Endoscopic Assessment 34%)e 38%)e Normalization of the endoscopic appearance of the mucosa (endoscopic remission) was defined as ES of 0. At Week 12 of UC1, a greater proportion of Prior biologic N=75 N=77 N=88 subjects treated with TREMFYA compared to placebo-treated subjects achieved and/or JAK 8% 38% 39% inhibitor failuref endoscopic remission (15% vs 5%). Fatigue Response Without prior N=115 N=111 N=102 In UC1, subjects treated with TREMFYA experienced a clinically meaningful biologic or JAK 23% 48% 56% inhibitor failureg improvement in fatigue, assessed by the PROMIS-Fatigue Short form 7a, at Week 12, compared to placebo-treated subjects. The effect of TREMFYA to improve Maintenance of Clinical Remission at Week 44 in subjects who achieved clinical fatigue after 12 weeks of induction has not been established. remission after 12 weeks of induction Maintenance Trial: UC2 Total populationk N=59 N=66 N=69 26% 38% The maintenance trial (UC2) evaluated 568 subjects who received one of two 34% 61% 72% (9%, (23%, intravenous TREMFYA induction regimens, including the recommended 200 mg 43%)l 54%)e regimen, for 12 weeks in Studies UC1 or UC3 (induction dose-finding study) and demonstrated clinical response per mMS after 12 weeks. Subjects were re- Prior biologic N=15 N=20 N=18 randomized to receive a subcutaneous maintenance regimen of either TREMFYA and/or JAK 27% 60% 56% inhibitor failuref 100 mg every 8 weeks, TREMFYA 200 mg every 4 weeks, or placebo for up to an additional 44 weeks. Without prior N=44 N=46 N=51 In UC2, 42% of subjects had failed (inadequate response, loss of response, or biologic or JAK 36% 61% 78% intolerance) treatment with one or more biologics or JAK inhibitors. inhibitor failurem The primary endpoint was clinical remission at Week 44 defined by mMS. Secondary endpoints included corticosteroid-free clinical remission, endoscopic improvement, histologic endoscopic mucosal improvement, all at Week 44 and maintenance of clinical remission at Week 44 in subjects who achieved clinical remission 12 weeks after intravenous TREMFYA induction treatment (see Table 9). 8 TREMFYA® (guselkumab) TREMFYA® (guselkumab) a T REMFYA 100 mg as a subcutaneous injection every 8 weeks after the induction 17 PATIENT COUNSELING INFORMATION regimen Advise the patient and/or caregiver to read the FDA-approved patient labeling b T REMFYA 200 mg as a subcutaneous injection every 4 weeks after the induction (Medication Guide and Instructions for Use) before starting TREMFYA therapy, and regimen each time the prescription is renewed, as there may be new information they need c A stool frequency subscore of 0 or 1 and not increased from induction baseline, a to know. rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability d Subjects who achieved clinical response 12 weeks following the intravenous Hypersensitivity Reactions administration of TREMFYA in either induction study UC1 or induction dose- Advise patients to discontinue TREMFYA and seek immediate medical attention if finding study UC3 they experience any symptoms of serious hypersensitivity reactions [see Warnings e p <0.001, adjusted treatment difference (95% CI) based on Cochran-Mantel- and Precautions (5.1)]. Haenszel method adjusted for randomization stratification factors Infections f Includes inadequate response, loss of response, or intolerance to biologic Instruct patients of the importance of communicating any history of infections to therapy (TNF blockers, vedolizumab) and/or a Janus kinase (JAK) inhibitor for ulcerative colitis the healthcare provider and contacting their healthcare provider if they develop g I ncludes subjects that were biologic and/or JAK inhibitor naïve and subjects any symptoms of an infection [see Warnings and Precautions (5.2)]. with biologic and/or JAK inhibitor exposure who did not meet criteria for failure. Immunizations Of these, 7 subjects in the placebo group, 6 subjects in the TREMFYA 100 mg Advise patients treated with TREMFYA to avoid use of live vaccines [see Warnings group, and 6 subjects in the TREMFYA 200 mg group were previously exposed to, and Precautions (5.4)]. but did not fail, a biologic or JAK inhibitor h N ot requiring any treatment with corticosteroids for at least 8 weeks prior to Instruction on Injection Technique week 44 and also meeting the criteria for clinical remission at week 44 Instruct patients or caregivers to perform the first self-injection under the i A n endoscopy subscore of 0 or 1 with no friability supervision and guidance of a qualified healthcare professional for proper training j An endoscopy subscore of 0 or 1 with no friability and Geboes score ≤3.1 in subcutaneous injection technique. Instruct patients who are self-administering (indicating neutrophil infiltration in <5% of crypts, no crypt destruction, and no to inject the full dose of TREMFYA/TREMFYA PEN [see Medication Guide and erosions, ulcerations, or granulation tissue) Instructions for Use]. k S ubjects who achieved clinical remission 12 weeks following intravenous Instruct patients or caregivers in the technique of proper needle and syringe administration of TREMFYA in either induction study UC1 or induction dose- disposal. Needles and syringes should be disposed of in a puncture-resistant finding study UC3 l p <0.01, adjusted treatment difference (95% CI) based on Cochran-Mantel- container. Advise patients and caregivers not to reuse needles or syringes. Haenszel method adjusted for randomization stratification factors Remind patients if they forget to take their dose of TREMFYA/TREMFYA PEN to m I ncludes subjects that were biologic and/or JAK inhibitor naïve and subjects inject their dose as soon as they remember. They should then take their next dose with biologic and/or JAK inhibitor exposure who did not meet criteria for failure. at the appropriate scheduled time. Of these, 3 subjects in the placebo group, 3 subjects in the TREMFYA 100 mg group, and 3 subjects in the TREMFYA 200 mg group were previously exposed to, Pregnancy but did not fail, a biologic or JAK inhibitor. Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in patients exposed to TREMFYA during pregnancy [see Use in Specific Study UC2 was not designed to evaluate the relationship of histologic endoscopic Populations (8.1)]. mucosal improvement at Week 44 to disease progression and long-term outcomes. Manufactured by: Endoscopic Assessment Janssen Biotech, Inc. Normalization of the endoscopic appearance of the mucosa (endoscopic Horsham, PA 19044, USA remission) was defined as ES of 0. In UC2, greater proportions of subjects treated US License No. 1864 with TREMFYA 100 mg every 8 weeks or TREMFYA 200 mg every 4 weeks achieved endoscopic remission at Week 44 compared to placebo-treated subjects (35% and For patent information: www.janssenpatents.com 34%, respectively, vs. 15%). © Johnson & Johnson and its affiliates 2017-2024 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied TREMFYA®/TREMFYA® PEN (guselkumab) injection is a clear and colorless to light yellow solution supplied as follows: Subcutaneous Injection • Carton of one 100 mg/mL single-dose One-Press patient-controlled injector (NDC: 57894-640-11) • C arton of one 200 mg/2 mL single-dose prefilled pen (TREMFYA PEN) (NDC: 57894-651-02) • Carton of one 100 mg/mL single-dose prefilled syringe with a 27G, half inch fixed needle assembled in a passive needle guard delivery system (NDC: 57894-640-01) • C arton of one 200 mg/2 mL single-dose prefilled syringe with a 27G, half inch fixed needle assembled in a passive needle guard delivery system (NDC: 57894- 651-22) Intravenous Infusion • Carton of one 200 mg/20 mL (10 mg/mL) single-dose vial (NDC: 57894-650-02) 16.2 Storage and Handling TREMFYA is sterile and preservative-free. Discard any unused portion. • Store in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF). • Store in original carton until time of use. • Protect from light until use. • Do not freeze. • Do not shake. • Not made with natural rubber latex. 9 Medication Guide TREMFYA® (trem fye´ ah) TREMFYA® (trem fye´ ah) PEN TREMFYA® (trem fye´ ah) (guselkumab) (guselkumab) (guselkumab) injection, for subcutaneous use injection, for subcutaneous use injection, for intravenous use What is the most important information I should know about TREMFYA? TREMFYA may cause serious side effects, including: • Serious allergic reactions. Stop using TREMFYA and get emergency medical help right away if you develop any of the following symptoms of a serious allergic reaction: ° fainting, dizziness, feeling lightheaded ° trouble breathing or throat tightness (low blood pressure) ° chest tightness ° swelling of your face, eyelids, lips, ° skin rash, hives mouth, tongue or throat ° itching • Infections. TREMFYA is a medicine that may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with TREMFYA and may treat you for TB before you begin treatment with TREMFYA if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with TREMFYA. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including: ° fever, sweats, or chills ° muscle aches ° weight loss ° cough ° warm, red, or painful skin or sores ° diarrhea or stomach pain ° shortness of breath on your body different from your ° burning when you urinate or ° blood in your phlegm (mucus) psoriasis urinating more often than normal See “What are the possible side effects of TREMFYA?” for more information about side effects. What is TREMFYA? TREMFYA is a prescription medicine used to treat adults: • with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light) • with active psoriatic arthritis (PsA). • with moderately to severely active ulcerative colitis It is not known if TREMFYA is safe and effective in children under 18 years of age. Do not use TREMFYA if you have had a serious allergic reaction to guselkumab or any of the other ingredients in TREMFYA. See the end of this Medication Guide for a complete list of ingredients in TREMFYA. Before using TREMFYA, tell your healthcare provider about all of your medical conditions, including if you: • h ave any of the conditions or symptoms listed in the section “What is the most important information I should know about TREMFYA?” • have an infection that does not go away or that keeps coming back. • have TB or have been in close contact with someone with TB. • have recently received or are scheduled to receive an immunization (vaccine). You should avoid receiving live vaccines during treatment with TREMFYA. • are pregnant or plan to become pregnant. It is not known if TREMFYA can harm your unborn baby. Pregnancy Registry: If you become pregnant during treatment with TREMFYA, talk to your healthcare provider about registering in the pregnancy exposure registry for TREMFYA. You can enroll in this registry by visiting www.mothertobaby.org/ongoing-study/ tremfya-guselkumab, by calling 1-877-311-8972, or emailing MotherToBaby@health.ucsd.edu. The purpose of this registry is to collect information about the safety of TREMFYA during pregnancy. • are breastfeeding or plan to breastfeed. It is not known if TREMFYA passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. 10 TREMFYA® (guselkumab) How should I use TREMFYA/TREMFYA PEN? See the detailed “Instructions for Use” that comes with TREMFYA/TREMFYA PEN for information on how to prepare and inject a dose of TREMFYA, and how to properly throw away (dispose of) the used TREMFYA prefilled syringe, One-Press injector or prefilled pen (TREMFYA PEN). • U se TREMFYA exactly as your healthcare provider tells you to use it. • I f you miss your TREMFYA dose, inject a dose as soon as you remember. Then, take your next dose at your regular scheduled time. Call your healthcare provider if you are not sure what to do. • I f you inject more TREMFYA than prescribed, call your healthcare provider right away. • A dults with plaque psoriasis or psoriatic arthritis will receive TREMFYA as an injection under the skin (subcutaneous injection). • Adults with ulcerative colitis will receive their starter doses with TREMFYA through a vein in the arm (intravenous infusion) in a healthcare facility by a healthcare provider. After completing the starter doses, patients will receive TREMFYA as an injection under the skin (subcutaneous injection). What are the possible side effects of TREMFYA? TREMFYA may cause serious side effects including: • See “What is the most important information I should know about TREMFYA?” The most common side effects of TREMFYA include: • respiratory tract infections • headache • injection site reactions • joint pain (arthralgia) • diarrhea • stomach flu (gastroenteritis) • fungal skin infections • herpes simplex infections • bronchitis These are not all the possible side effects of TREMFYA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store TREMFYA? • Store TREMFYA in the refrigerator between 36°F to 46°F (2°C to 8°C). • Keep TREMFYA in the original carton to protect it from light until time of use. • TREMFYA is not made with natural rubber latex. • Do not freeze TREMFYA. • Do not shake TREMFYA. Keep TREMFYA and all medicines out of the reach of children. General information about the safe and effective use of TREMFYA. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TREMFYA for a condition for which it was not prescribed. Do not give TREMFYA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about TREMFYA that is written for health professionals. What are the ingredients in TREMFYA? Active ingredient: guselkumab Inactive ingredients: Single-dose prefilled syringe, single-dose One-Press patient-controlled injector, single-dose prefilled pen for subcutaneous use: L-histidine, L-histidine monohydrochloride monohydrate, polysorbate 80, sucrose and water for injection. Single- dose vial for intravenous infusion: EDTA disodium dihydrate, L-histidine, L-histidine monohydrochloride monohydrate, L-methionine, polysorbate 80, sucrose and water for injection. Manufactured by: Janssen Biotech, Inc., Horsham, PA 19044, USA, U.S. License Number 1864 For patent information: www.janssenpatents.com © Johnson & Johnson and its affiliates 2017-2024 For more information, call 1-800-526-7736 or go to www.tremfya.com. This Medication Guide had been approved by the U.S. Food and Drug Administration. Revised: 09/2024 11 TREMFYA® (guselkumab) Instructions for Use TREMFYA® (trem fye´ ah) (guselkumab) SINGLE-DOSE Prefilled Syringe Important TREMFYA comes as a single-dose prefilled Prefilled syringe parts syringe containing one 100 mg dose. Each TREMFYA prefilled syringe can only be used Before use one time. Throw the used prefilled syringe away (See Step 3) after one dose, even if Plunger there is medicine left in it. Do not reuse your Do not hold or pull plunger at TREMFYA prefilled syringe. any time. If your healthcare provider decides that you or a caregiver may be able to give your injections of TREMFYA at home, you should Safety guard receive training on the right way to prepare and inject TREMFYA using the prefilled Finger flange syringe before attempting to inject. Do not Body try to inject yourself until you have been Hold syringe body below shown the right way to give the injections by finger flange. your healthcare provider. Viewing window Read this Instructions for Use before using your TREMFYA prefilled syringe and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or Needle cover your treatment. Do not remove until you are ready to inject TREMFYA The TREMFYA prefilled syringe is intended (See Step 2). for injection under the skin, not into the muscle or vein. After injection, the needle will retract into the body of the device and After use lock into place. Plunger locks Safety guard Storage information activates Store in refrigerator at 36° to 46°F (2° to 8°C). You will need these supplies: • 1 TREMFYA prefilled syringe Do not freeze TREMFYA prefilled syringe. Not provided in the TREMFYA Keep TREMFYA prefilled syringe and all prefilled syringe carton: medicines out of reach of children. • 1 Alcohol swab Do not shake your TREMFYA prefilled syringe. Needle • 1 Cotton ball or gauze pad retracts • 1 Adhesive bandage Keep TREMFYA prefilled syringe in the into the • 1 Sharps container original carton to protect from light and body (See Step 3) physical damage. 12 TREMFYA® (guselkumab) 1. Prepare for your injection Inspect carton Choose injection site Clean injection site Remove your TREMFYA prefilled Select from the following areas Wash your hands well with soap syringe carton from the for your injection: and warm water. refrigerator. Keep the prefilled • Front of thighs (recommended) Wipe your chosen injection site syringe in the carton and let it sit on a flat surface at room • Lower stomach area (lower with an alcohol swab and allow temperature for at least 30 abdomen), except for a 2-inch it to dry. minutes before use. area right around your navel Do not touch, fan, or blow on (belly-button) the injection site after you have Do not warm the prefilled syringe any other way. • Back of upper arms (only if cleaned it. someone else is giving you the Check the expiration date (‘EXP’) injection) on the back panel of the carton. Do not inject into skin that is Do not use your prefilled syringe tender, bruised, red, hard, thick, if the expiration date has passed. scaly or affected by psoriasis. Do not inject TREMFYA if the perforations on the carton are broken. Call your healthcare provider or pharmacist for a refill. Inspect liquid Take your TREMFYA prefilled syringe out of the carton. Check the TREMFYA prefilled syringe liquid in the viewing window. It should be clear to slightly yellow and may contain tiny white or clear particles. You may also see one or more air bubbles. This is normal. Do not inject if the liquid is cloudy or discolored, or has large particles. Call your healthcare provider or pharmacist for a refill. 13 TREMFYA® (guselkumab) 2. Inject TREMFYA using prefilled syringe 45° Remove needle cover Position fingers and Release pinch and Hold your prefilled syringe by insert needle reposition hand the body and pull needle cover Place your thumb, index and Use your free hand to grasp the straight off. It is normal to see a middle fingers directly under the body of the prefilled syringe. drop of liquid. finger flange, as shown. Inject TREMFYA within 5 minutes Do not touch plunger or area of removing the needle cover. above finger flange as this may Do not put needle cover back on, cause the needle safety device as this may damage the needle or to activate. cause a needle stick injury. Use your other hand to pinch Do not touch needle or let it touch skin at the injection site. Position any surface. syringe at about a 45 degree angle to the skin. Do not use a TREMFYA prefilled syringe if it is dropped. Call It is important to pinch enough your healthcare provider or skin to inject under the skin and not into the muscle. Press plunger pharmacist for a refill. Insert needle with a quick, dart- Place thumb from the opposite like motion. hand on the plunger and press the plunger all the way down until it stops. Release pressure from plunger The safety guard will cover the needle and lock into place, removing the needle from your skin. 14 TREMFYA® (guselkumab) How should I dispose of the used 3. After your injection prefilled syringe? If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: • made of a heavy-duty plastic • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out • upright and stable during use • leak-resistant • properly labeled to warn of hazardous Dispose of your prefilled Check injection site waste inside the container syringe There may be a small amount When your sharps disposal container is almost full, you will need to follow your Put your used TREMFYA prefilled of blood or liquid at the community guidelines for the right way syringe in an FDA-cleared sharps injection site. Hold pressure to dispose of your sharps disposal disposal container right away over your skin with a cotton container. There may be state or local after use. ball or gauze pad until any bleeding stops. laws about how you should throw away Do not throw away (dispose of) used needles and syringes. your TREMFYA prefilled syringe in Do not rub the injection site. For more information about safe sharps your household trash. If needed, cover injection site disposal, and for specific information Do not recycle your used sharps with a bandage. about sharps disposal in the state that disposal container. you live in, go to the FDA’s website at: For more information, see Need help? www.fda.gov/safesharpsdisposal “How should I dispose of the This Instructions for Use has been approved used prefilled syringe?” Call your healthcare provider by the U.S. Food and Drug Administration. to talk about any questions Manufactured by: you may have. For additional Janssen Biotech, Inc. assistance or to share your Horsham, PA 19044 feedback call 800-JANSSEN US License No. 1864 (800-526-7736). Approved: December 2017 15 TREMFYA® (guselkumab) INSTRUCTIONS FOR USE TREMFYA® [trem fye’ ah] (guselkumab) injection, for subcutaneous use One-Press Patient-Controlled Injector This “Instructions for Use” contains information on how to inject TREMFYA. Important Information You Please read this Instructions for Use before using your One-Press injector and each time you get a new Need to Know Before Injecting One-Press injector. There may be new information. TREMFYA This leaflet does not take the place of talking with your healthcare provider about your medical condition or your TREMFYA comes in a single-dose One-Press injector treatment. containing one 100 mg dose. During injection, push handle all the way down Storage information until teal body is not visible to inject the full dose. DO NOT LIFT ONE-PRESS during injection. If you Store in refrigerator at 36° to 46°F (2° to 8°C). do, the One-Press will lock and you will not get Do not freeze your One-Press injector. the full dose. Do not shake your One-Press injector. Each One-Press injector can only be used one time. Throw Keep your One-Press injector and all medicines out of away (See Step 3) after one dose, even if there is medicine reach of children. left in it. Do not reuse your One-Press injector. Keep your One-Press injector in the original carton to protect from light and physical damage. If your healthcare provider decides that you or a caregiver may be able to give your injections of TREMFYA at home, you should receive training on the right way to prepare Need help? and inject TREMFYA using the One-Press injector. Do not Call your healthcare provider to talk about any questions try to inject yourself until you have been trained by your healthcare provider. you may have. For additional assistance or to share your feedback call 800-JANSSEN (800-526-7736). 16 TREMFYA® (guselkumab) One-Press injector parts Before use After use H andle Handle is Pressed all the way down. Teal Body The teal body Window is not visible. After lifting, Needle Guard the needle guard locks and the yellow band is Bottom Cap visible. Remove cap Do not lift during before injecting the injection. (see Step 2). You will need: • 1 One-Press injector Not provided in the carton: • 1 Alcohol swab • 1 Cotton ball or gauze pad • 1 Adhesive bandage • 1 Sharps container (See Step 3) 17 TREMFYA® (guselkumab) 1. Preparing to Inject TREMFYA Inspect carton and allow Check the expiration date Choose injection site TREMFYA to come to room (‘EXP’) on the carton Select from the following areas temperature Do not use your One-Press for your injection: Remove your One-Press injector injector if the expiration date • Front of thighs (recommended) carton from the refrigerator. has passed. • Lower stomach area (lower Keep your One-Press injector in Do not inject TREMFYA if the abdomen), except for a 2-inch the carton and let it sit on a flat seal on the carton is broken. area right around your navel surface at room temperature for Call your healthcare provider (belly-button) at least 30 minutes before use. or pharmacist for a new Do not warm your One-Press One-Press injector. • Back of upper arms (only if someone else is giving you the injector any other way. injection) Do not inject into skin that is tender, bruised, red, hard, thick, scaly, or affected by psoriasis. 18 TREMFYA® (guselkumab) 1. Preparing to Inject TREMFYA (continued) Wash hands Inspect liquid in window Wash your hands well with Take your One-Press injector soap and warm water. out of the carton. Check the liquid in the window. Clean injection site It should be clear to slightly Wipe your chosen injection site yellow and may contain tiny with an alcohol swab and allow white or clear particles. You it to dry. may also see one or more air Do not touch, fan, or blow on bubbles. This is normal. the injection site after you have Do not inject if the liquid is: cleaned it. • cloudy, • discolored, or • has large particles. Call your healthcare provider or pharmacist for a new One-Press injector. 19 TREMFYA® (guselkumab) 2. Injecting TREMFYA Pull off bottom cap Place straight on skin. Confirm your injection is Keep hands away from the Push handle all the way down complete needle guard after the cap is until teal body is not visible Your injection is complete removed. It is normal to see a when: few drops of liquid. DO NOT LIFT ONE-PRESS during • The teal body is not visible. Inject TREMFYA within injection! 5 minutes of removing the cap. If you do, the needle guard will • You cannot press the handle Do not put the cap back on. lock, showing a yellow band, and down anymore. you will not get the full dose. • You may hear a click. This could damage the needle. Do not use a One-Press injector You may hear a click when the if it is dropped after removing injection begins. Keep pushing. the cap. Call your healthcare If you feel resistance, keep pushing. provider or pharmacist for a This is normal. new One-Press injector. The medication injects as you push. Do this at a speed that is comfortable for you. Lift straight up The yellow band indicates that the needle guard is locked. 20 TREMFYA® (guselkumab) Disposing of TREMFYA 3. After your injection One-Press injector If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: • made of a heavy-duty plastic • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out • upright and stable during use • leak-resistant • properly labeled to warn of Dispose of your Check injection site hazardous waste inside the One-Press injector container There may be a small amount of Put your used One-Press injector blood or liquid at the injection When your sharps disposal container is in a sharps disposal container site. Hold pressure over your skin almost full, you will need to follow your right away after use. with a cotton ball or gauze pad community guidelines for the right way to dispose of your sharps disposal Do not throw away (dispose of) until any bleeding stops. container. There may be state or local your One-Press injector in your Do not rub the injection site. laws about how you should throw away household trash. If needed, cover injection site used needles and syringes. Do not recycle your used sharps with a bandage. For more information about safe sharps disposal container. disposal, and for specific information For more information, see about sharps disposal in the state that “Disposing of TREMFYA you live in, go to the FDA’s website at: One-Press injector”. www.fda.gov/safesharpsdisposal. You may also consult your pharmacist. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured by: Janssen Biotech, Inc. Horsham, PA 19044 US License No. 1864 Revised: June 2023 21 TREMFYA® (guselkumab) Instructions for Use TREMFYA® (trem fye´ ah) (guselkumab) SINGLE-DOSE injection, for subcutaneous use 200mg/2mL Prefilled Syringe This Instructions for Use contains information on how to inject TREMFYA. Important Information Prefilled syringe parts You Need to Know Before Before use Injecting TREMFYA Plunger TREMFYA comes in a single-dose prefilled Do not hold or pull plunger at syringe containing one 200 mg dose. any time. If your healthcare provider decides that you or a caregiver may be able to give your injections of TREMFYA at home, you should Safety guard receive training on the correct way to prepare and inject TREMFYA before using Finger flange the prefilled syringe. Body Read this Instructions for Use before using your TREMFYA prefilled syringe and each time Viewing window you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment. Needle Each TREMFYA prefilled syringe can only be used one time. Throw the used prefilled Needle cover syringe away (see Step 4) after one dose, Do not remove until you are even if there is still medicine left in it. Do not ready to inject (See Step 3). reuse your TREMFYA prefilled syringe. The TREMFYA prefilled syringe is intended for injection under the skin, not into the muscle After use or vein. After injection, the needle will retract Plunger locks into the device and lock into place. Safety guard Storage information activates You will need: Store in refrigerator between 36°F to 46°F • 1 prefilled syringe (2°C to 8°C). Not provided in the carton: Do not freeze TREMFYA prefilled syringe. • Alcohol swabs Do not shake your TREMFYA prefilled syringe. • Cotton balls or gauze pads Keep TREMFYA prefilled syringe and all Needle • Adhesive bandages medicines out of reach of children. retracts • Sharps container into the (See Step 4) Keep TREMFYA prefilled syringe in the original body carton to protect from light and physical damage. 22 TREMFYA® (guselkumab) 1. Get ready 2. Prepare to inject TREMFYA WAIT 3MI0N Allow TREMFYA to come Take the prefilled syringe out of Choose injection site to room temperature and the carton. Select from the following areas inspect carton Inspect liquid to see that for your injection: Remove the carton from the it is clear and colorless to • Front of thighs refrigerator and let the carton slightly yellow • Lower stomach area (lower sit on a flat surface at room Check the liquid in the viewing abdomen), except for a 2-inch temperature for approximately window. It should be clear and area right around your navel 30 minutes before use. colorless to slightly yellow and (belly-button) Do not warm the prefilled syringe may contain tiny white or clear • Back of upper arms (only if someone any other way. particles. You may also see air else is giving you the injection) Check the expiration (‘EXP’) date. bubbles. This is normal. Do not inject into skin that is tender, Do not use your prefilled syringe Do not inject if the liquid is: bruised, red, scaly, thick or hard. Avoid if the expiration date has passed • cloudy or areas with scars or stretch marks. or if the seal on the carton is • discolored or broken. Contact your healthcare provider or pharmacist for a new • has large particles prefilled syringe. Do not use the prefilled syringe if it is dropped. Call your healthcare provider or pharmacist for a new prefilled syringe. Wash hands and clean injection site Wash your hands well with soap and warm water. Wipe your chosen injection site with an alcohol swab and allow it to dry. Do not touch, fan, or blow on the injection site after you have cleaned it. 23 TREMFYA® (guselkumab) 3. Inject TREMFYA 45° Remove needle cover when Pinch injection site and Release pressure from you are ready to inject insert needle at about a plunger to remove the Hold the prefilled syringe by 45-degree angle needle from the skin the body and pull needle cover It is important to pinch enough The needle will retract into the straight off. It is normal to see a skin to inject under the skin and device and lock into place. few drops of liquid. not into muscle. Inject TREMFYA within 5 minutes Insert needle with a quick dart- of removing the needle cover. like motion. Do not put needle cover back on, as this may damage the needle or cause a needle stick injury. Do not touch needle or let it touch SLOWLY any surface. Do not use the prefilled syringe if it is dropped. Call your healthcare provider or pharmacist for a new prefilled syringe. Do not hold or pull the plunger at any time. Slowly press plunger all the way down until it stops to inject all of the liquid You will feel some resistance as you press the plunger, this is normal. 24 TREMFYA® (guselkumab) Disposing of TREMFYA prefilled 4. After your injection syringe If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: • made of heavy-duty plastic • can be closed with a tight-fitting, puncture resistant lid, without sharps being able to come out • upright and stable during use • leak-resistant • properly labeled to warn of hazardous Check injection site Dispose of your prefilled waste inside the container There may be a small amount of syringe When your sharps disposal container blood or liquid at the injection is almost full, you will need to follow Put the used prefilled syringe site. Gently hold pressure over your community guidelines for the right in an FDA-cleared sharps the injection site with a cotton way to dispose of your sharps disposal disposal container right away ball or gauze pad until any container. There may be state or local after use. bleeding stops. laws about how you should throw away Do not throw away (dispose used needles and syringes. Do not rub the injection site. of) your prefilled syringe in If needed, cover the injection site your household trash. For more information about safe sharps with a bandage. disposal, and for specific information Do not recycle your used about sharps disposal in the state that sharps disposal container. you live in, go to the FDA’s website at: For more information, see www.fda.gov/safesharpsdisposal. You Disposing of TREMFYA may also consult your pharmacist. prefilled syringe. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Need help? Manufactured by: Janssen Biotech, Inc. Call your healthcare provider Horsham, PA 19044, USA to talk about any questions US License No. 1864 you may have. For additional assistance or to share your feedback, call 800-526-7736. Approved: September 2024 25 uassuel TREMFYA® (guselkumab) INSTRUCTIONS FOR USE TREMFYA® PEN [trem fye’ ah Pen] (guselkumab) injection, for subcutaneous use 200mg/2mL Prefilled Pen This Instructions for Use contains information on how to inject TREMFYA PEN. SINGLE-DOSE Important Information You Storage information Need to Know Before Injecting Store in refrigerator between 36° to 46°F (2° to 8°C). TREMFYA PEN Do not freeze your TREMFYA PEN. TREMFYA PEN comes in a single-dose Prefilled Pen Do not shake your TREMFYA PEN. containing one 200 mg dose. Keep your TREMFYA PEN and all medicines out of reach If your healthcare provider decides that you or a caregiver of children. may be able to give your injections of TREMFYA PEN at Keep your TREMFYA PEN in the original carton to protect home, you should receive training on the correct way to from light and physical damage. prepare and inject TREMFYA PEN before using the Prefilled Pen. Read this Instructions for Use before using your Prefilled Pen and each time you get a new Prefilled Pen. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment. Each TREMFYA PEN can only be used one time. Throw the used Prefilled Pen away (see Step 4) after one dose, even if there is still medicine left in it. Do not reuse your Prefilled Pen. 26 TREMFYA® (guselkumab) TREMFYA PEN parts Before use You will need: • 1 Prefilled Pen Not provided in the carton: • Alcohol swabs After use • Cotton balls or gauze pads Plunger rod fills • Adhesive bandages the viewing • Sharps container (See Step 4) window Viewing Window Yellow Needle Guard Thin Hidden Needle Cap Do not remove until you are ready to inject (See Step 3) 27 TREMFYA® (guselkumab) 1. Get ready 2. Prepare to Inject TREMFYA PEN WAIT 30 MIN Allow TREMFYA PEN to Take your Prefilled Pen out of Choose injection site come to room temperature the carton. Select from the following areas for and inspect carton Inspect liquid in window your injection: Remove the carton from the to see that it is clear and • Front of thighs refrigerator and let the carton colorless to slightly yellow • Lower stomach area (lower sit on a flat surface at room Check the liquid in the viewing abdomen), except for a 2-inch temperature for approximately window. It should be clear and area right around your navel 30 minutes before use. colorless to slightly yellow and (belly-button) Do not warm the Prefilled Pen may contain tiny white or clear • Back of upper arms (only if any other way. particles. You may also see air someone else is giving you Check the expiration (‘EXP’) date. bubbles. This is normal. the injection) Do not use the Prefilled Pen if Do not inject if the liquid is: Do not inject into skin that is tender, the expiration date has passed • cloudy or bruised, red, scaly, thick or hard. Avoid or if the seal on the carton is • discolored or areas with scars or stretch marks. broken. Contact your healthcare provider or pharmacist for a new • has large particles Prefilled Pen. Call your healthcare provider or pharmacist for a new Prefilled Pen. Wash hands and clean injection site Wash your hands well with soap and warm water. Wipe your chosen injection site with an alcohol swab and allow it to dry. Do not touch, fan, or blow on the injection site after you have cleaned it. 28 TREMFYA® (guselkumab) 3. Inject TREMFYA PEN 10 SEC ist CLICK! 2nd CLICK! Remove cap when you are Position the Prefilled Pen Keep holding your ready to inject straight onto the injection Prefilled Pen firmly site then push and hold against the skin for about Do Not Touch Yellow the Prefilled Pen 10 seconds to hear a Needle Guard! second click This may start the injection Do Not Lift The Prefilled Pen and you will not receive You are almost done. During Injection! the dose. If you do, the yellow needle guard will lock and the full Pull the cap straight off. It is dose will not be delivered. normal to see a few drops of liquid. Position your Prefilled Pen Inject TREMFYA PEN within straight onto the injection site 5 minutes of removing cap. with the yellow needle guard Do not put the cap back on as against the skin and the this may damage the needle. viewing window facing you. Do not use your Prefilled Pen Press down on the Prefilled if it is dropped after removing Pen and keep holding it down the cap. Call your healthcare against the skin. provider or pharmacist for a You will hear the first click. new Prefilled Pen. 29 | TREMFYA® (guselkumab) Disposing of TREMFYA PEN 3. Inject TREMFYA PEN (continued) If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: • made of heavy-duty plastic • can be closed with a tight-fitting, puncture resistant lid, without sharps being able to come out • upright and stable during use • leak-resistant • properly labeled to warn of hazardous Keep holding firmly against waste inside the container Lift straight up the skin and confirm your When your sharps disposal container is injection is complete almost full, you will need to follow your community guidelines for the right way Your injection is complete when to dispose of your sharps disposal the plunger rod stops moving container. There may be state or local and fills the viewing window. laws about how you should throw away used needles and syringes. For more information about safe sharps 4. After your injection disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: www.fda.gov/safesharpsdisposal. You may also consult your pharmacist. Need help? Call your healthcare provider to talk about any questions you may have. For additional assistance or to share your feedback, call 800-526-7736. Check injection site Dispose of your Prefilled Manufactured by: Janssen Biotech, Inc. There may be a small amount of Pen and cap Horsham, PA 19044, USA blood or liquid at the injection Put your used Prefilled Pen and cap US License No. 1864 site. Gently hold pressure over in an FDA-cleared sharps disposal This Instructions for Use has been the injection site with a cotton container right away after use. approved by the U.S. Food and Drug ball or gauze pad until any Do not throw away (dispose of) your Administration bleeding stops. Prefilled Pen in your household trash. Approved: September 2024 Do not rub the injection site. If Do not recycle your used sharps needed, cover the injection site disposal container. cp-126899v9 with a bandage. For more information, see Janssen Disposing of TREMFYA PEN. 30, including , for TREMFYA^® and discuss any questions that you have with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Dosage Forms and Strengths: TREMFYA^® is available in a 100 mg/mL prefilled syringe and One-Press patient-controlled injector for subcutaneous injection, a 200 mg/2 mL prefilled syringe and prefilled pen (TREMFYA^® PEN) for subcutaneous injection, and a 200 mg/20 mL (10 mg/mL) single dose vial for intravenous infusion.

ABOUT JOHNSON & JOHNSON
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

Janssen Research & Development, LLC and Janssen Biotech, Inc. are Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA^®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future evevents or developments.

Footnotes
¹ National Psoriasis Foundation. About psoriasis. Available at: https://www.psoriasis.org/children-with-psoriasis/. Accessed October 2024.

² Bronckers IM, Paller AS, van Geel MJ, van de Kerkhof PC, Seyger MM. Psoriasis in Children and Adolescents: Diagnosis, Management and Comorbidities. Paediatr Drugs. 2015 Oct;17(5):373-84. doi: 10.1007/s40272-015-0137-1.

³ Brunello, Francesco et al. New Insights on Juvenile Psoriatic Arthritis. Frontiers in pediatrics. 2022. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC9199423/#:~:text=Juvenile%20psoriatic%20arthritis%20(JPsA)%20is,Idiopathic%20Arthritis%20(JIA)%20population. Accessed October 2024.

⁴ ClinicalTrials.gov.A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR). Identifier: NCT03451851. Available at: https://clinicaltrials.gov/study/NCT03451851

⁵ Clinicaltrials.gov. A Study of Guselkumab in the Treatment of Participants With Moderate to Severe Plaque-Type Psoriasis (VOYAGE 1). Identifier NCT02207231. https://www.clinicaltrials.gov/ct2/show/NCT02207231. Accessed October 2024.

⁶ Clinicaltrials.gov. A Study of Guselkumab in the Treatment of Participants With Moderate to Severe Plaque-Type Psoriasis With Randomized Withdrawal and Retreatment (VOYAGE 2). Identifier NCT02207244. https://www.clinicaltrials.gov/ct2/show/NCT02207244. Accessed October 2024.

⁷ ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti-Tumor Necrosis Factor (TNF) Alpha Agent(s) (DISCOVER 1). Identifier: NCT03162796. Available at: https://clinicaltrials.gov/ct2/show/NCT03162796. Accessed October 2024.

⁸ ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis. Identifier: NCT03158285. Available at: https://clinicaltrials.gov/ct2/show/NCT03158285. Accessed October 2024.

⁹ TREMFYA^® Prescribing Information. Available at: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TREMFYA-pi.pdf. Accessed October 2024.

Media contact:
Craig Stoltz
+1 215-779-9396
cstoltz@its.jnj.com

Investor contact:
Lauren Johnson
investor-relations@its.jnj.com