ZYMFENTRA

1 INDICATIONS AND USAGE ZYMFENTRA is a tumor necrosis factor (TNF) blocker indicated in adults for maintenance treatment of: moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously. ( 1 ) moderately to severely active Crohn’s disease following treatment with an infliximab products administered intraneously. ( 1 ) ZYMFENTRA is indicated in adults for maintenance treatment of: moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously. moderately to severely active Crohn's disease following treatment with an infliximab product administered intravetnously.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious infections [ see Warnings and Precautions ( 5.1 ) ] Malignancies [ see Warnings and Precautions ( 5.2 ) ] Hepatitis B virus reactivation [ see Warnings and Precautions ( 5.3 ) ] Hepatotoxicity [ see Warning and Precautions ( 5.4 ) ] Congestive heart failure [ see Warnings and Precautions ( 5.5 ) ] Hematologic reactions [ see Warnings and Precautions ( 5.6 ) ] Hypersensitivity and other administration reactions [ see Warnings and Precautions ( 5.7 ) ] Neruologic reactions [ see Warnings and Precautions ( 5.8 ) ] Autoimmunity [ see Warnings and Precautions ( 5.11 ) ] Most common adverse reactions (>3%) are: Ulcerative Colitis: COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain. ( 6.1 ) Crohn's Disease: COVID-19, headache, upper respiratory tract infection, injection site reaction, diarrhea, increased blood creatine phosphokinase, arthralgia, increased alanine aminotransferase, hypertension, urinary tract infection, neutropenia, dizziness, and leukopenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact CELLTRION USA, Inc. at 1-800-560-9414 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to ZYMFENTRA in 518 adult subjects in two 54-weekrandomized, double-blind, placebo-controlled trials in subjects with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) (UC Trial I an CD Trial I). Subject who achieved clinical response following three induction doses of infliximab-dyyb administered as an intravenous infusion at Week 0, 2 and 6 were randomized 2:1 to ZYMFENTRA 120 mg or placebo as a subcutaneous injection every two weeks at Week 10 [ see Clinical Studies ( 14.1 and 14.2 )]. Ulcerative Colitis The most common adverse reactions reported in ≥3% of subjects and at a higher rate than Placebo in UC Trial I are shown in Table 1. Table 1 Adverse Reactions a in the Maintenance Phase of a Randomized, Double-Blind 54-Week Study of Subjects with UC (UC Tral I) ZYMFENTRA 120 mg Subcutaneous Injection b N=296 (%) Placebo N=140 (%) COVID-19 10 6 Anemia d 5 4 Arthralgia 4 1 Injection site reaction e 3 2 Increased alanine aminotransferase 3 1 Abdominal pain f 3 1 a reported in at least 3% of ZYMFENTRA-treated subjects and at a higher than placebo b ZYMFENTRA 120 mg as a subcutaneous injection every two weeks starting Week 10 following 3 intravenous induction doses of inflixiab-dyyb c Includes: COVID-19 and COVID-19 pneumonia d Includes: anemia and iron deficiency anemia e Some subjects had multiple occurences of injection site reactions. In this table, injection site reactions are counted only once per subject. Symptoms in individual subjects included one or more of injection site bruising, edema, erythema, induration, pain, pruritus and swelling. f Includes: abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal discomfort Crohn's Disease The most common adverse reactions reported in ≥3% of subjects and at a higher rate than placebo in CD Trial I are shown in Table 2. Table 2 Adverse Reactions a in the Maintenance Phase of a Randomized, Double-Blind 54-Week Study of Subjects with CD (CD Trial I) ZYMFENTRA 120 mg Subcutaneous Injection b N=222 (%) Placebo N=101 (%) COVID-19 10 5 Headache 8 4 Upper respiratory track infectionsd c 7 3 Injection site reaction d 5 1 Diarrhea 5 1 Increased blood creatine phosphokinase 4 2 Arthralgia 4 3 Increased alaine aninotransferase 4 1 Hypertensions e 3 2 Urinary track infection f 3 2 Neutropenia 3 0 Dizziness 3 0 Leukopenia 3 0 a reported in at least 3% of ZYMFENTRA-treated subjects and at a higher rate than placebo b ZYMFENTRA 120 mg administered subcutaneously starting at Week 10 and every 2 weeks thereafter for up to Week 54. c Includes: upper respiratory tract infection, acute sinusitis, chronic sinusitis, influenza like illness, nasopharyngitis, pharyngitis, pharyngitis streptococcal, rhinitis, rhinorrhea, rhinovirus infection, sinusitis, tonsillitis d Some subjects had multiple occurrences of injection site reactions. In this table, injection site reactions are counted only once per subject. Symptoms in individual subjects included one or more of injection site bruising, edema, erythema, induration, pain, pruritus, rash, swelling, warmth. e Includes: hypertension and essential hypertension f Includes: urinary tract infection, pyelonephritis Adverse Reactions of Special Interest Infections In UC Trial I, at leaset one serious infection was reported in 3% of ZYMFENTRA-treated subjects compared to 1% in the plaebo group. Serious infections in the ZYMFENTRA-treated subjects were COVID-19, cystitis, pneumonia, salpingitis, and urinary tract injection [ see Warnings and Precautions ( 5.1 ) ]. In CD Trial I, infections were observed in 30% of ZYMFENTRA-treated subjects compare to 17% of placebo-treated subjects. At least one serious infection was reported in 3% of ZYMFENTRA-treated subjects compared to 1% in the placebo group. Serious infections in the ZYMFENTRA-treated subjects were abscess, appendicitis, bacterial arthritis, bartholinitis, bronchiolitis, and urinary tract infection [ see Warnings and Precautions ( 5.1 ) ]. Malignancies In UC Trial I, malignancy (prostate cancer) was reported in a ZYMFENTRA-treated subject. No malignancies were reported among placebo-treated subjects [ see Warnings and Precautions ( 5.2 ) ]. In another clinical trial in patients with CD, one malignancy (non-small cell lung cancer) was reported in a ZYMFENTRA-treated subject [ see Warnings and Precautions ( 5.2 ) ]. Hepatotoxicity Three cases of drug induced liver injury were noted in ZYMFENTRA-treated subjects that led to study drug discontinuation [ see W arnings and Precautions ( 5.4 ) ]. In two subjects in UC Trial I, ALT and AST levels started rising 7 to 12 months after starting ZYMFENTRA, reaching peak values of 4 to 11x ULN for ALT, and 2 to 7x ULN for AST. In both subjects, total bilirubin levels remains below 2x ULN. In one subject in CD Trial I, ALT and AST started rising within a month after starting ZYMFENTRA, reaching peack values of 18x ULN for ALT and 14.9x ULN for AST. At approximately 5 months, total bilirubin level also increased to a peak value of 2.5x ULN. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of outside of the U.S with a non-U.S approved infliximab product administered subcutaneously. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections and infestations: cellulitis, disseminated tuberculosis, lower respiratory tract infection, pneumonia, sepsis Neoplasms benign, malignant and unspecified: breast cancer, gastric cancer, lung cancer Nervous system disorders: multiple sclerosis General disorders and administration site conditions : fatigue, malaise The following additional adverse ractions have been identified during post-approval use of infliximab products administered intravenously. Neutropenia, agranuloxytosis (including infants exposed in utero to infliximab products), idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura. Interstitial lung disease (including pulmonary fibrosis/interstitial pneumonitis and rapidly progessive disease). Pericardial effusion, systemic and cutaneous vasculitis. Erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, linear IgA bullous dermatosis (LABD), acute generalized exanthematous pustulosis (AGEP), new onset and worsening psoriasis (all subtypes including pustular, primarily palmoplantar), lichenoid react. Peripheral demyelinating disorders (such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy) transverse myelitis, and neuropathies (additional neurologic reactions have also been observed). Acute liver failure, jaundice, hepatitis, and cholestasis. Serious infections and vaccine breakthrough infection including bovine tuberculosis (disseminated BCG infection) following vaccination in an infant exposed in utero to infliximab products. Malignancies, including leukemia, melanoma, Merkel cell carcinoma, and cervical cancer. Anaphylactic reactions, including anaphylactic shock, laryngeal/pharyngeal edema and severe bronchospasm, and seizure. Transient visual loss has been reported in association with infliximab products during or within 2 hours of infusion. Cerebrovascular accidents, myocardial ischemia/infarction (some fatal), and arrhythmia occurring within 24 hours of initiation of infusion have also been reported.

4 CONTRAINDICATIONS ZYMFENTRA is contraindicated in patients with a history of a severe hypersensitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients in ZYMFENTRA, or any murine proteins. Reactions have included anaphylaxis [ see Warnings and Precautions ( 5.7 ) ]. History of severe hypersentitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients in ZYMFENTRA or to any murine proteins. ( 4 )

11 DESCRIPTION Infliximab-dyyb, a tumor necrosis factor (TNF) blocker, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions). It has a molecular weight of approximately 145.9 kDa. Infliximab-dyyb is produced by a recombinant murine myeloma cell line, SP2/0. ZYMFENTRA (inifliximab-dyyb) injection for subcutaneous use is a sterile, preservative-free, clear to opalescent, colorless to pale brown solution. ZYMFENTRA is supplied in a single-dose prefilled syringe with 29 gauge fixed 1/2 inch needle, prefilled syringe with 29 gauge fixed 1/2 inch needle with needle guard, or prefilled pen with 27 gauge fixed 1/2 inch needle. Each mL of solution contains 120 mg infliximab-dyyb, acetic acid (0.19 mg), polysorbate 80 (0.5 mg), sodium acetate (0.56 mg), sorbitol (45 mg) and Water for Injection, USP. The pH is 5.0.

2 DOSAGE AND ADMINISTRATION Important Dosage Information. ( 2.1 ). ZYMFENTRA is indicated as maintenance treatment only, starting at Week 10 and thereafter. ▫ All patients must complete an intravenous induction regimen with an infliximab product before starting ZYMFENTRA. ZYMFENTRA is for subcutaneous use only. Recommeneded Maintenance Dosage in Ulcerative Colitis and Crohn's Direase ( 2.2 ) Week 10 and thereafter : Inject 120 mg subcutaneously once every two weeks. To switch patients who are responding to maintenance therapy with an infliximab product administered intravenously, administer the first subcutaneous dose of ZYMFENTRA in place of the next scheduled intravenous infusion and every two weeks thereafter. See the full prescribing information on how to administer subcutaneously. ( 2.3 ) 2.1 Important Dosage Information ZYMFENTRA is indicated as maintenance treatment only, starting at Week 10 and thereafter. ▫ All patients mush coplete an intravenous induction regimen with an infliximab product before starting ZYMFENTRA. For induction dosing information, see the corresponding full prescribing information for the chosen infliximab product. ZYMFENTRA is for subtutaneous use only. 2.2 Recommeneded Dosage for Maintenance Treatment in Ulcerative and Colitis Crohn's Disease Maintenance dosage starting at Week 10 and thereafter: 120 mg subcutaneously once every two weeks. To switch patients who are responding to maintenance therapy with an infliximab product administered intravenously, administer the first subcutaneous dose of ZYMFNETRA in place of the next scheduled intravenous infusion and every two weeks thereafter. 2.3 Subcutaenous Administration Instructions ZYMFENTRA is intended for use under the guidance and supervision of a healthcare professional. If a healthcare professional determines that it is appropriate, patients may self-inject ZYMFENTRA or caregivers may inject ZYMFENTRA using either the ZYMFENTRA prefilled syringe, ZYMFENTRA prefilled syringe with needle guard, or ZYMFENTRA prefilled pen after proper training in subcutaenous injection technique. Parental drug products should be inspected visually for particulate matter and discoloration prior to administration, whether solution and container permit. ZYMFENTRA should be a clear, colorless to pale brown solution. Do not use if particulates or discoloration is present. Inject into the front of the thighs, the abdomen excepts for the 2 inches around the navel, or the outer area of the upper arms (caregiver only). Rotate the injection site each time an injection is given. Allow at least 1.2 inches between the new injection site and the previous inejction site. Never inject into areas where the skin is red, bruised, tender, or indurated. Do not use the syringe or pen of it has been dropped or is visibly damaged. A damaged syringe may not function proprely. Do not resue or shake the syringe or pen at any time. Mixed Dose If an injection of ZYMFENTRA is missed, inject the next subcutaneous dose as soon as possible and then every two weeks thereafter.

7 DRUG INTERACTIONS 7.1 Other Biological Products Used to Treat UC and CD The concurrent use of ZYMFENTRA with other immunosuppressive biological products used to treat UC and CD may increase the risk of infection and is not recommended [ see Warnings and Precautions ( 5.9 ) ]. Consider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA [ see Warnings and Precautions ( 5.10 ) ]. 7.2 Cytochrome P450 Substrates The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-1, IL-6, IL-10, IFN) during chronic inflammation. Therefore, ZYMFENTRA, an antagonist of TNFα, could normalize the formation of CYP450 enzymes potentially resulting in a decrease in exposure of CYP450 substrates. Upon initiation or discontinuation of TNF blockers, including ZYMFENTRA, in patients being treated with CYP450 substrates requiring therapeutic drug monitoring, monitor therpeutic parameters (e.g., INR for warfarin) or drug concentration (e.g., cyclosporine or theophylline). Dosage adjustment may be needed to maintain drug concentrations or parameters within the therapeutic range. See prescribing information for specific drugs. 7.3 Live Vaccines/Therapeutic Infectious Agents It is recommended that live vaccines not be given concurrently with ZYMFENTRA. It is also recommended that live vaccines not be given to infants after in utero exposure to infliximab products for 6 months following birth [ see Warnings and Precautions ( 5.12 ) ]. It is recommended that therapeutic infectious agents not be given concurrently with ZYMFENTRA [ see Warnings and Precautions ( 5.12 ) ].

12 CLINICAL PHAMACOLOGY 12.1 Mechanism of Action Infliximab-dyyb neutralize the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibit binding of TNFα with its receptors. Infliximab-dyyb has shown biological activities, such as TNFα neutralization activity and TNFα binding affinities, complement 1q (C1q) binding affinity and crystallizable fragment (Fc) receptor binding affinities in a wide variety of in vitro bioasays. The relationship of these biological response markers to the mechanism(s) by which infliximab-dyyb exerts its clinical effects is unknown. 12.2 Pharmacodynamics No formal pharmacodynamic studies have been conducted. 12.3 Phamacokinetics Following single and multiple subcutaneous dosing of infliximab-dyyb, exposures to infliximab-dyyb (i.e., AUC) are proportionally increased over the dose range from 120 mg to 240 mg (2 times the recommended dosage). After a single subcutaneous dose of infliximab-dyyb 120 mg in healthy subjects, the median (SD) C max and AUC inf were 10.0 (3.2) mcg/mL and 6945.6 (2830.2) mcg·h/mL, respectively. Following recommended subcutaneous maintenance dose of ZYMFENTRA (120 mg every 2 weeks) in adult subjects with UC and CD from Week 10 after intravenous induction treatment with infliximab-dyyb, steady-state was achieved by Week 22, and the mean (SD) trough serum concentrations of infliximab-dyyb at steady-state were 14.6 (7.8) mcg/mL and 14.6 (8.9) mcg/mL in subjects with UC and CD, respectively. Pharmacokinetics are comparable between healthy subjects, and subjects with UC or CD. Absorption In healthy subjects, the median time to reach the maximum serum concentration (T max ) was 7 days after a single subcutaneous dose of infliximab-dyyb 120 mg. In healthy subjects, AUC inf following a single subcutaneous dosed of infliximab-dyyb 120 mg was approximately 23% relative to a single intravenous dose of infliximab-dyyb 5 mg/kg. Following infliximab-dyyb 120 mg subcuaneosly every 2 weeks, steady state AUC for 8-week internal was 25-35% higher compared to infliximab-dyyb 5 mg/kg administered intravenously every 8 weeks in subjects with UC and CD. Distribution Population pharmacokinetic analyses showed that the volume of distribution of infliximab-dyyb was 3.36 L. Elimination In healthy subjects, the mean half-life was 332 hours after a single subcutaneous dose of infliximab-dyyb 120 mg. Populatoin pharmacokinetic analyses showed that the clearance of infliximab-dyyb was 0.013 L/hr and the clearance was increased in the presence of anti-drug antibody. The metabolic pathway of infliximab has not been characterized. As a IgG1κ monoclonal antibody, infliximab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. Specific Populations Weight Population pharmacokinetic analysis indicated that exposure to infliximab-dyyb was inversely related to body weight. However, the magnitude of body weight effect on systemic exposure was not clinically meaningful in adult subjects with UC and CD weighing from 39 to 130 kg. Age, Sex and Race Age (≥65 years ofld), sex, or race did not have a clinically meaningful effect on pharmacokinetics of infliximab-dyyb. Drug Interaction Studies Population pharmacokinetic analysis showed that co-administered methotrexate did not have clinically meaningful effect on the pharmacokinetics of infliximab-dyyb. 12.6 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Difference in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of infliximab-dyyb or of other infliximab products. In UC and CD clinical studies (UC Trial I and CD Trial I), approximately 64% subjects developed anti-drug antibodies to infliximab-dyyb following induction treatment with infliximab-dyyb intravenously and maintenance treatment with ZYMFENTRA by Week 54 [183/287 (64%) in subjects with UC, and 151/232 (65%) in subjects with CD] [see Clinical Studies ( 14 ) ]. Among subjects with anti-drug antibodies, 92% had neutralizing antibodies [161/183 (88%) subjects with UC, and 147/151 (97%) subjects with CD]. Use of concomitant immunosuppressant agents (azathioprine, 6-mercaptopurine and methotrexate) appeared to reduce the frequency of ADA to infliximab-dyyb. Anti-Drug Antibody Effects on Pharmacokinetics Subjects who were positive for anti-drug antibodies showed lower infliximab-dyyb trough seum concentrations of infliximab-dyyb by approximately 30 to 40% compared to subjects who were negative for anti-drug antibodies. In some subjects with high titers of anti-drug antibodies and positive neutralizing antibodies, trough seum concentrations of infliximab-dyyb were below the lower limit of quantitation (<0.1 mcg/mL). There was no identified clinically significant effect of anti-drug antibodies on the safety and effectiveness of ZYMFENTRA in Study UC I and Study CD I.

12.1 Mechanism of Action Infliximab-dyyb neutralize the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibit binding of TNFα with its receptors. Infliximab-dyyb has shown biological activities, such as TNFα neutralization activity and TNFα binding affinities, complement 1q (C1q) binding affinity and crystallizable fragment (Fc) receptor binding affinities in a wide variety of in vitro bioasays. The relationship of these biological response markers to the mechanism(s) by which infliximab-dyyb exerts its clinical effects is unknown.

12.2 Pharmacodynamics No formal pharmacodynamic studies have been conducted.

12.3 Phamacokinetics Following single and multiple subcutaneous dosing of infliximab-dyyb, exposures to infliximab-dyyb (i.e., AUC) are proportionally increased over the dose range from 120 mg to 240 mg (2 times the recommended dosage). After a single subcutaneous dose of infliximab-dyyb 120 mg in healthy subjects, the median (SD) C max and AUC inf were 10.0 (3.2) mcg/mL and 6945.6 (2830.2) mcg·h/mL, respectively. Following recommended subcutaneous maintenance dose of ZYMFENTRA (120 mg every 2 weeks) in adult subjects with UC and CD from Week 10 after intravenous induction treatment with infliximab-dyyb, steady-state was achieved by Week 22, and the mean (SD) trough serum concentrations of infliximab-dyyb at steady-state were 14.6 (7.8) mcg/mL and 14.6 (8.9) mcg/mL in subjects with UC and CD, respectively. Pharmacokinetics are comparable between healthy subjects, and subjects with UC or CD. Absorption In healthy subjects, the median time to reach the maximum serum concentration (T max ) was 7 days after a single subcutaneous dose of infliximab-dyyb 120 mg. In healthy subjects, AUC inf following a single subcutaneous dosed of infliximab-dyyb 120 mg was approximately 23% relative to a single intravenous dose of infliximab-dyyb 5 mg/kg. Following infliximab-dyyb 120 mg subcuaneosly every 2 weeks, steady state AUC for 8-week internal was 25-35% higher compared to infliximab-dyyb 5 mg/kg administered intravenously every 8 weeks in subjects with UC and CD. Distribution Population pharmacokinetic analyses showed that the volume of distribution of infliximab-dyyb was 3.36 L. Elimination In healthy subjects, the mean half-life was 332 hours after a single subcutaneous dose of infliximab-dyyb 120 mg. Populatoin pharmacokinetic analyses showed that the clearance of infliximab-dyyb was 0.013 L/hr and the clearance was increased in the presence of anti-drug antibody. The metabolic pathway of infliximab has not been characterized. As a IgG1κ monoclonal antibody, infliximab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. Specific Populations Weight Population pharmacokinetic analysis indicated that exposure to infliximab-dyyb was inversely related to body weight. However, the magnitude of body weight effect on systemic exposure was not clinically meaningful in adult subjects with UC and CD weighing from 39 to 130 kg. Age, Sex and Race Age (≥65 years ofld), sex, or race did not have a clinically meaningful effect on pharmacokinetics of infliximab-dyyb. Drug Interaction Studies Population pharmacokinetic analysis showed that co-administered methotrexate did not have clinically meaningful effect on the pharmacokinetics of infliximab-dyyb.

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3 DOSAGE FORMS AND STRENGTHS ZYMFENTRA (infliximab-dyyb) is a clear, colorless to pale brown solution available as follow: Injection: 120 mg/mL in a single-dose prefilled syringe. Injection: 120 mg/mL in a single-dose prefilled syringe with needle guard. Injection: 120 mg/mL in a single-dose prefilled pen. Injection ( 3 ): 120 mg/mL in a single-dose prefilled syringe. 120 mg/mL in a single-dose prefilled syringe with needle guard. 120 mg/mL in a single-dose prefilled pen.

ZYMFENTRA infliximab-dyyb INFLIXIMAB INFLIXIMAB ACETIC ACID SODIUM ACETATE SORBITOL polysorbate 80 ZYMFENTRA infliximab-dyyb INFLIXIMAB INFLIXIMAB ACETIC ACID SODIUM ACETATE SORBITOL polysorbate 80

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies of infliximab-dyyb have not been conducted to evaluate the carcinogenic potential or its effect on fertility.

BLA761358

ZYMFENTRA

infliximab-dyyb

72606-047

HUMAN PRESCRIPTION DRUG

SUBCUTANEOUS

PRINCIPAL DISPLAY PANEL - 120 mg/mL Prefilled Pen Label NDC 72606-025-01 Rx only Zymfentra TM infliximab–dyyb injection Subcutaneous use CELLTRION Inc. PRINCIPAL DISPLAY PANEL - 120 mg/mL Prefilled Pen Label

Manufactured by: CELLTRION, Inc. 23, Academy-ro, Yeonsu-gu, Incheon 22014, Republic of Korea U.S. License No. 1996 Distributed by: CELLTRION USA, Inc. One Evertrust Plaza Suite 1207, Jersey City, New Jersey, 07302, USA CELLTRION USA, Inc. © CELLTRION, Inc.

17 PATIENT COUNSELING INFORMATION Advise the patient or thier caregiver to read the FDA-Approved Patient Labeling (Medication Guide and Instructions for Use). Patients or their caregivers should be advised of the potential benefits and risks of ZYMFENTRA. Healthcare providers should instruct their patients or their caregivers to read the Medication Guide before starting ZYMFENTRA therapy and to reread it each time they receive an injection. Infections Inform patients that ZYMFENTRA increases the risk for developing serious infections. Instruct patients of the importance of contacting their healthcare provider if they develop any symptoms of an infection, including tuberculosis, invasive fungal infections, and reactivation of hepatitis B virus infections [ see Warnings and Precautions ( 5.1 , 5.3 ) ]. Malignancies Malignancies have been reported among children, adolescents and young adults who received treatment with TNF blockers. Patients should be counseled about the risk of lymphoma and other malignancies while receiving ZYMFENTRA [ see Warnings and Precautions ( 5.2 ) ]. Hepatotoxicity Instruct patients to seek medical attention if they develop signs or symptoms of hepatotoxicity (e.g., jaundice) [ see Warnings and Precautions ( 5.4 ) ]. Congestive Heart Failure Instruct patients to seek medical attention and consult their prescriber if they develop signs or symptoms of heart failure [ see Warnings and Precautions ( 5.5 ) ]. Hematologic Reactions Instruct patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever) while on ZYMFENTRA [ see Warnings and Precautions ( 5.6 ) ]. Hypersensitivity Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [ see Warnings and Precautions ( 5.7 ) ]. Neurologic Reactions Advise patients to seek medical attention if they develop signs or symptoms of neurologic reactions [ see Warnings and Precautions ( 5.8 ) ]. Live Vaccines/Therapeutic Infectious Agents Instruct ZYMFENTRA-treated patients to avoid receiving live vaccines or therapeutic infectious agents [ see Warnings and Precautions ( 5.12 ) ] Administration Instruct patients to follow sharp disposal recommendations, as described in the Instructions for Use.

INSTRUCTIONS FOR USE ZYMFENTRA (Zim fen' trah) (infliximab-dyyb) Injection for subcutaneous use only Single-Dose Prefilled Pen 120 mg/mL Rx Only Read and follow the Instructions for Use that come with your ZYMFENTRA Prefilled Pen before you start using it and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. Figure A: Parts of ZYMFENTRA Prefilled Pen Important Information Use the Prefilled Pen only if your healthcare provider has trained you on the right way to prepare for and to give an injection. Ask your healthcare provider how often you will need to give an injection. Rotate the injection site each time you give an injection. Each new injection site should be at least 1.2 inches away from the previous injection site. Do not shake the Prefilled Pen at any time. Do not remove the Cap until you are ready to inject. Do not share the Prefilled Pen with anyone. How to store the Prefilled Pen Store the Prefilled Pen in a refrigerator between 36°F to 46°F (2°C to 8°C). Keep the Prefilled Pen in the original carton until use to protect it from light. Do not use the Prefilled Pen that has been left in direct sunlight. Do not freeze the Prefilled Pen. If the Prefilled Pen has been frozen, do not use the Prefilled Pen even if it is thawed. Do not warm the Prefilled Pen using heat sources such as hot water or a microwave. Let the Prefilled Pen naturally warm at room temperature between 68°F to 77°F (20°C to 25°C) for 30 minutes before giving an injection. If needed, you may store the Prefilled Pen at room temperature between 68°F to 77°F (20°C to 25°C) for up to 14 days. When the Prefilled Pen has reached room temperature, do not put it back in the refrigerator. The Prefilled Pen must be thrown away (discarded) if not used within the 14 days. Keep the Prefilled Pen and all medicines out of the reach of children. Prepare for the Injection 1. Gather the supplies for the injection. 1a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. 1b. Remove 1 Prefilled Pen from the carton stored in your refrigerator. Note: Return the carton with any unused Prefilled Pens to refrigerator immediately after taking out one Prefilled Pen. 1c. Make sure you have the following supplies: - Prefilled Pen - 1 Alcohol swab Not included in the carton: - 1 Cotton ball or gauze - 1 Adhesive bandage - FDA-cleared sharps disposal container 2. Inspect the Prefilled Pen. 2a. Make sure you have the correct medicine (ZYMFENTRA). 2b. Check the expiration (EXP) date on the label of the Prefilled Pen (See Figure B). 2c. Look at the Prefilled Pen and make sure it is not cracked or damaged. Do not use the Prefilled Pen if: - it is cracked or damaged. - the expiration (EXP) date has passed. Figure B 3. Inspect the Medicine. 3a. Look through the Window and make sure that the liquid is clear, colorless to pale brown, and free of particles (see Figure C). Do not use the Prefilled Pen if the liquid is the discolored (yellow or dark brown), cloudy, or contains particles in it. You may see air bubbles in the liquid. This is normal. Figure C 4. Wait 30 minutes. 4a. Leave the Prefilled Pen at room temperature 68°F to 77°F (20°C to 25°C) for 30 minutes to allow it to warm up (see Figure D). Do not warm the Prefilled Pen using heat sources such as hot water or a microwave. Figure D 5. Choose an injection site (see Figure E). 5a. You may inject into: - the front of your thighs. - the stomach area (abdomen) except for the 2 inches around the belly button (navel). - the outer area of the upper arm if you are a caregiver. Do not inject into skin that is within 2 inches of your belly button (navel), or is red, hard, tender, damaged, bruised, or scarred. Do not inject through your clothes. 5b. Rotate the injection site each time you give an injection. Do not inject the same injection site each time you give an injection. Each new injection site should be at least 1.2 inches away from the injection site you used before. Figure E 6. Wash your hands. 6a. Wash your hands with soap and water and dry them thoroughly (see Figure F). Figure F 7. Clean the injection site. 7a. Clean the injection site with an alcohol swab using a circular motion (see Figure G). 7b. Let the skin dry before injecting. Do not blow on or touch the injection site again before giving the injection. Figure G Give the injection 8. Remove the Cap. 8a. Hold the Prefilled Pen by the injector body with the Cap on top using one hand. Gently pull the Cap straight off with the other hand. Do not recap the Prefilled Pen. Do not remove the Cap until you are ready to inject. Do not touch the Needle or Needle Cover. Doing so may result in a needle stick injury. 8b. Throw away (dispose of) the Cap in an FDA cleared sharps container (see Step 12 and Figure H). Figure H 9. Place the Prefilled Pen on the injection site. 9a. Hold the Prefilled Pen so that you can see the Window. 9b. Without pinching or stretching the skin, place the Prefilled Pen over the injection site at a 90-degree angle (see Figure I). Figure I 10. Give the injection (see Figure J). 10a. Press the Prefilled Pen firmly against the skin. When the injection starts you will hear the first loud "click" and the purple Plunger Rod will begin to fill the Window. 10b. Keep holding the Prefilled Pen firmly against the skin and listen for the second loud "click." This can take up to 10 seconds. Do not change the position of the Prefilled Pen after the injection has started. 10c. After you hear the second loud "click" continue to hold the Prefilled Pen firmly against the skin and count slowly to 5 to make sure you inject the full dose. 10d. Look at the Prefilled Pen and make sure that the purple Plunger Rod is filling the Window completely. Figure J 11. Remove the Prefilled Pen from your skin. 11a. Remove the Prefilled Pen from your skin (see Figure K). After you remove the Prefilled Pen from the injection site, the needle will be automatically covered (see Figure L). If the Window has not turned completely purple or if the medicine is still injecting, this means you have not received a full dose. Call your healthcare provider immediately. You may see grey stopper in the Window. This is normal. Some bleeding may occur. Do not reuse the Prefilled Pen. Do not rub the injection site Figure K Figure L After the Injection 12. Throw away (dispose of) the Prefilled Pen. 12a. Put the used Prefilled Pen in an FDA-cleared sharps disposal container right away after use (see Figure M). Do not throw away (dispose of) the Prefilled Pen in your household trash. 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, and - properly labeled to warn of hazardous waste inside the container. When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of it. There may be state or local laws about how you should throw away used needles and pens. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal. Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container. Figure M 13. Care for the injection site. 13a. Treat the injection site by gently pressing, not rubbing, a cotton ball or gauze to the site and apply an adhesive bandage, if necessary. Manufactured by: CELLTRION, Inc., 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea US License Number 1996 Distributed by: CELLTRION USA, Inc., 1 Evertrust Plaza Suite 1207, Jersey City, NJ 07302 Figure A Figure B Figure C Figure D Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M

This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 02/2024 MEDICATION GUIDE ZYMFENTRA TM (Zim fen' trah) (infliximab-dyyb) injection, for subcutaneous use Read the Medication Guide that comes with ZYMFENTRA before you receive the first treatment, and before each time you receive a treatment of ZYMFENTRA. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment. What is the most important information I should know about ZYMFENTRA ? ZYMFENTRA may cause serious side effects, including: 1. Risk of infection ZYMFENTRA is a medicine that affects your immune system. ZYMFENTRA can lower the ability of your immune system to fight infections. Serious infections have happened in patients receiving ZYMFENTRA. These infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections. Your doctor should test you for TB before starting ZYMFENTRA. Your doctor should monitor you closely for signs and symptoms of TB during treatment with ZYMFENTRA. Before starting ZYMFENTRA, tell your doctor if you: think you have an infection. You should not start receiving ZYMFENTRA if you have any kind of infection. are being treated for an infection. have signs of an infection, such as a fever, cough, flu-like symptoms. have any open cuts or sores on your body. get a lot of infections or have infections that keep coming back. have diabetes or an immune system problem as people with these conditions have a higher chance for getting infections. have TB, or have been in close contact with someone with TB. live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis); these infections may develop or become more severe if you receive ZYMFENTRA. If you do not know if you have lived in an area where histoplasmosis, coccidioidomycosis, or blastomycosis is common, ask your doctor. have or have had hepatitis B. use the medicines KINERET (anakinra), ORENCIA (abatacept), or other medicines called biologics used to treat the same conditions as ZYMFENTRA. After starting ZYMFENTRA, if you have an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. ZYMFENTRA can make you more likely to get infections or make any infection that you have worse. 2. Risk of Cancer There have been cases of unusual cancers in children and teenage patients using tumor necrosis factor (TNF) blocker medicines, such as ZYMFENTRA. For people receiving TNF blocker medicines, including ZYMFENTRA, the chances of getting lymphoma or other cancers may increase. Some people receiving TNF blockers, including ZYMFENTRA, developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn's disease or ulcerative colitis with a TNF blocker and another medicine called azathioprine or 6-mercaptopurine. People who have been treated for Crohn's disease and ulcerative colitis, for a long time may be more likely to develop lymphoma. This is especially true for people with very active disease. Some people treated with infliximab products, such as ZYMFENTRA, have developed certain kinds of skin cancer. If any changes in the appearance of your skin or growths on your skin occur during or after your treatment with ZYMFENTRA, tell your doctor. Patients with Chronic Obstructive Pulmonary Disease (COPD), a specific type of lung disease, may have an increased risk for getting cancer while being treated with ZYMFENTRA. Tell your doctor if you have ever had any type of cancer. Discuss with your doctor any need to adjust medicines you may be taking. See the section " What are the possible side effects of ZYMFENTRA ?" below for more information. What is ZYMFENTRA? ZYMFENTRA is a prescription medicine used as an injection uner the skin (subcutaneous injection) by adults for the maintenance treatment of: moderately to severely active ulcerative colitis following treatment with an infliximab product given by intravenous infusion (IV). moderately to severely active Crohn's disease following treatment with an infliximab product given by intravenous infusion (IV). It is not known if ZYMFENTRA is safe and effective in children under 18 years of age . Do not take ZYMFNETRA if you: have had an allergic reaction to ZYMFENTRA, other infliximab products, any murine proteins or any of the ingredients in ZYMFENTRA. See the end of this Medication Guide for a complete list of ingredients in ZYMFENTRA. Before you receive ZYMFENTRA, tell your doctor all of your medical conditions, including if you: have an infection (see " What is the most important information I should know about ZYMFENTRA ? "). have other liver problems including liver failure. have heart failure or other heart conditions. If you have heart failure, it may get worse while you receive ZYMFENTRA. have or have had any type of cancer. have COPD (Chronic Obstructive Pulmonary Disease), a specific type of lung disease. Patients with COPD may have an increased risk of getting cancer while receiving ZYMFENTRA. have or have had a condition that affects your nervous system such as: - multiple sclerosis, or Guillain-Barré syndrome, or - if you experience any numbness or tingling, or - if you have had a seizure. have recently received or are scheduled to receive a vaccine. Adults receiving ZYMFENTRA should not receive live vaccines (for example, the Bacille Calmette-Guérin [BCG] vaccine) or treatment with a weakened bacteria (such as BCG for bladder cancer). Adults should have all of their vaccines brought up to date before starting treatment with ZYMFENTRA. are pregnant or plan to become pregnant, are breastfeeding or plan to breastfeed. You and your doctor should decide if you should receive ZYMFENTRA while you are pregnant or breastfeeding. If you have a baby and you were receiving ZYMFENTRA during your pregnancy, it is important to tell your baby's doctor and other healthcare professionals about your ZYMFENTRA use so they can decide when your baby should receive any vaccine. Certain vaccinations can cause infections. If you received ZYMFENTRA while you were pregnant, your baby may be at higher risk for getting an infection. If your baby receives a live vaccine within 6 months after birth, your baby may develop infections with serious complications that can lead to death. This includes live vaccines such as the BCG, rotavirus, or any other live vaccines. For other types of vaccines, talk with your doctor. How should I receive ZYMFENTRA ? Use ZYMFENTRA exactly as your doctor tells you to. - ZYMFENTRA is provided as a single-dose prefilled syringe, single-dose prefilled syringe with needle guard or single-dose prefilled pen. Your healthcare provider will prescribe the type that is best for you. - If your healthcare provider decides that you or your cargiver can give your injections of ZYMFENTRA at home, you or your caregiver should be shown the right way to prepare and inject ZYMFENTRA. - Do not try to inject ZYMFENTRA yourself until you or your caregiver have been shown how to inject ZYMFENTRA by your healthcare provider. - ZYMFENTRA is injected under your skin (subcutaneously) 1 time every two weeks. - Inject ZYMFENTRA under the skin (subcutaneous injection), in your upper arms, stomach area (abdomen), or upper legs (thighs). - Do no give an injection in an area of the skin that is tender, bruised, red or hard. - Use a different injection site each time you use ZYMFENTRA. - If you are not able to inject ZYMFENTRA at your regular scheduled time or you miss a dose of ZYMFENTRA, inject the dose as soon as possible. Then, inject your next dose every two weeks thereafter. If you are not sure when to inject ZYMFENTRA, call your healthcare provider. - If you inject more than prescribed, call your doctor right away. - Be sure to keep all of your scheduled follow-up appointments. Read the detailed Instructions for Use at the end of this Medication Guide for insructions about how to prepare and inject a dose of ZYMFENTRA, and how to properly throw away (dispose of) used needles and syringes. The syringe and needle must never be re-used. After the rubber stopper is puntured, ZYMFENTRA can become contaiminated by harmful bacteria which could cause an infection if re-used. Therefore, throw away any unused portion of ZYMFENTRA . What should I avoid while taking ZYMFENTRA? Do not take ZYMFENTRA together with other medicines called biologics that are used to treat the same conditions as ZYMFENTRA. Tell your doctor about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. These include any other medicines to treat Crohn's disease, or ulcerative colitis. Know the medicines you take. Keep a list of your medicines and show them to your doctor and pharmacist when you get a new medicine. What are the possible side effects of ZYMFENTRA ? ZYMFENTRA can cause serious side effects, including (see " What is the most important information I should know about ZYMFENTRA ? "): Serious Infections Some patients, especially those 65 years and older have had serious infections while receiving infliximab products, such as ZYMFENTRA. These serious infections include TB and infections caused by viruses, fungi, or bacteria that have spread throughout the body or cause infections in certain areas (such as skin). Some patients die from these infections. If you get an infection while receiving treatment with ZYMFENTRA your doctor will treat your infection and may need to stop your ZYMFENTRA treatment. Tell your doctor right away if you have any of the following signs of an infection while receiving or after receiving ZYMFENTRA: a fever feel very tired have a cough have flu-like symptoms warm, red, or painful skin Your doctor will examine you for TB and perform a test to see if you have TB. If your doctor feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with ZYMFENTRA and during treatment with ZYMFENTRA. Even if your TB test is negative, your doctor should carefully monitor you for TB infections while you are receiving ZYMFENTRA. Patients who had a negative TB skin test before receiving infliximab products may develop active TB after receiving infliximab products. If you are a chronic carrier of the hepatitis B virus, the virus can become active while you are being treated with ZYMFENTRA. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor should do a blood test for hepatitis B virus before you start treatment with ZYMFENTRA, while you are being treated and for several months after you finish treatment. Tell your doctor if you have any of the following symptoms: feel unwell poor appetite tiredness (fatigue) fever, skin rash, or joint pain Liver Injury Some patients receiving infliximab products have developed serious liver problems. Tell your doctor if you have: jaundice (skin and eyes turning yellow) dark, brwon-colored urine pain on the right side of your stomach area (right-sided abdominal pain) fever extreme tiredness (sevre fatigue) Heart Failure If you have a heart problem called congestive heart failure, your doctor should check you closely while you are receiving ZYMFENTRA. Your congestive heart failure may get worse while you are receiving ZYMFENTRA. Be sure to tell your doctor of any new or worse symptoms including: shortness of breath swelling of ankles or feet sudden weight gain Treatment with ZYMFENTRA may need to be stopped if you get new or worse congestive heart failure. Blood Probelms In some patiens receiving infliximab products, the body may not make enough of the blood cells tha help fight infections or help stop bleeding. Tell your doctor if you: have a fever that does not go away bruise or bleed very easily look very pale Allergic Reactions Some patients have had allergic reactions to infliximab products. Some of these reactions were severe. These reactions can happen while you are getting your ZYMFENTRA treatment or shortly afterward. Your doctor may need to stop or pause your treatment with ZYMFENTRA and may give you medicines to treat the allergic reaction. Signs of an allergic reaction can include: hives (red, raised, itchy patches of skin) difficulty breathing chest pain high or low blood pressure fever chills Some patients treated with infliximab products have had delayed allergic reactions. Tell your doctor right away if you have any of these signs of delayed reaction to ZYMFENTRA: fever rash headache sore throat muscle or joint pain swelling of the face and hands difficulty swallowing Nervous System Disorders Some patients receiving infliximab products have developed problems with their nervous system. Tell your doctor if you have: changes in your vision numbness or tingling in any part of your body seizures weakness in your arms or legs Some patients have experienced a stroke within approximately 24 hours of their infusion with infliximab products. Tell your doctor right away if you have symptoms of a stroke which may include numbness or weakness of the face, arm, or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes, sudden trouble walking, dizziness, loss of balance or coordination or a sudden, severe headache. Lupus-like Syndrome Some patient have developed symptoms that are like the symptoms of Lupus. If you develop any of the following symptoms, your doctor may decide to stop your treatment with ZYMFENTRA: chest disomfort or pain that does not go away shortness of breath joint pain rash on the cheeks or arms that gets worse in the sun The most common side effects of ZYMFENTRA include: COVID-19 respiratory infections, such as sinus infections and sore throat injection site reactions headache abdominal pain abnormal liver enzymes joint pain diarrhea high blood pressure urinary tract infections dizziness Tell your doctor about any side effect that bothers you or does not go away. These are not all of the side effects with ZYMFENTRA. Ask your doctor or pharmacist for more information. 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 ZYMFENTRA? Store ZYMFENTRA prefilled syringes and prefilled pens in a refrigerator between 36°F to 46°F (2°C to 8°C). If needed, ZYMFENTRA prefilled syringes and prefilled pens may be stored at room temperature between 68°F to 77°F (20°C to 25°C) for up to 14 days with protection from light. When ZYMFENTRA prefilled syringes and prefilled pens have reached room temperature, do not put ZYMFENTRA back in the refrigerator. ZYMFENTRA must be thrown away (discarded) if not used within the 14 days. Do not freeze ZYMFENTRA. Do not shake ZYMFENTRA. Keep ZYMFENTRA in the original carton until ready to use to protect it from light. General information about ZYMFENTRA Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your doctor or pharmacist for information about ZYMFENTRA that is written for health professionals. Do not use ZYMFENTRA for a condition for which it was not prescribed. Do not give ZYMFENTRA to other people, even if they have the same symptoms that you have. For more information call 1-888-804-3433. What are the ingredients in ZYMFENTRA? The active ingredient is infliximab-dyyb. The inactive ingredients in ZYMFENTRA include acetic acid, polysorbate 80, sodium acetate, and sorbitol in water for injections. No preservatives are present. Manufactured by: CELLTRION, Inc. 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea U.S. License No. 1996 © CELLTRION, Inc. Distributed by CELLTRION USA, Inc. One Evertrust Plaza Suite 1207, Jersey City, New Jersey, 07302, USA For more information call 1-888-804-3433

14 CLINICAL STUDIES 14.1 Adult Ulcerative Colitis The safety and efficacy of ZYMFENTRA were assessed in a randomized, double-blind, placebo-controlled clinical trial (UC Trial I; NCT04205643 ) in adult subjects with moderately to severely active UC (defined as a modified Mayo score [mMS] between 5 to 9 with an endoscopic subscore [ES] of 2 or 3). The mMS is a 3-component Mayo score (0-9), which consists of following subscores (0 to 3 for each subscore): stool frequency (SFS), rectal bleeding (RBS), and findings on centrally read endoscopy score (ES). An ES of 2 was defined by marked erythema, lack of vascular pattern, any friability, and/or erosions, and a score of 3 was defined by spontaneous bleeding and ulceration. Subjects had demonstrated an inadequate response or intolerance to treatment with corticosteroids alone or in combination with 6-mercaptopurine or azathioprine. Subjects were permitted to use stable doses of oral aminosalicylates, oral corticosteroids (prednisone ≤20 mg/day or equivalent, budesonide ≤9 mg/day), UC-related antibiotics, and/or immunomodulatory agents (azathioprine, 6-mercaptopurine, or methotrexate). Corticosteroid tapering was permitted after Week 10. All subjects received three intravenous induction doses of 5 mg/kg of infliximab-dyyb at Weeks 0, 2 and 6. In order to be randomized to treatment in UC Trial I, subjects had to be in clinical response at Week 10. Clinical response was defined as a decrease from baseline in the mMS of at least 2 points and at least 30%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1 point. A total of 438 subjects were randomized at Week 10 in a double-blind fashion (2:1) to ZYMFENTRA 120 mg as a subcutaneous injection or placebo every two weeks. At the time of randomization into the double-blind phase (Week 10), 92% were receiving aminosalicylates, 41% were receiving oral corticosteroids, and 22% were receiving immunomodulators including AZA, 6-MP or MTX. A total of 10% of randomized subjects had prior exposure to biological poucts or JAK inhibitors. Subjects in the boule-blind phase had a mean age of 39 years (range 18 to 75 years); 44% were female; and 98% identified as White, and 2% as American Indian or Alaska Native. The primary endpoint was the proportion of subjects in clinical remission at Week 54. Secondary endpoints included the proportion of subjects achieving histologic-endoscopic mucosal improvement and corticosteroid-fee remission at Week 54 (see Table 3 ). Table 3: Proportion of Subjects with Ulcerative Colitis Meeting Efficacy Endpoints at Week 54 in UC Trial I Endpoint ZYMFENTRA Placebo Treatment Difference a and 95% CI Clinical Remission b at Week 54 Total population N=294 43% N=144 21% 21% (12, 29) No prior biological product/JAK inhibitor exposure N=265 45% N=131 21% Prior biological product/JAK inhibitor exposure N=29 31% N=13 15% Histologic-Endoscopic Mucosal Improvement d at Week 54 Total population N=294 36% N=144 17% 18% (9, 26) No prior biological product/JAK inhibitor exposure N=265 36% N=131 18% Prior biological product/JAK inhibitor exposure N=29 31% N=13 8% Corticosteroid-Free Remission e at Week 54 Total population N=120 37% N=61 18% 17% f (3, 29) No prior biological product/JAK inhibitor N=107 36% N=56 18% Prior biological product/JAK inhibitor exposure N=13 39% N=5 20% CI = confidence interval, JAK = Janus kinase a Treatement difference (adjusted for stratification factors of previous exposure to biological product and/or JAK inhibitor, use of treatment with oral corticosteoids Week 0, and clinical remission status at Week 10.) b Clinical remission is defined using the mMS as SFS of 0 or 1 point; RBS of 0 point; and ES of 0 or 1 point (excluding friability). c p < 0.0001 d Histologic-endoscopic mucosal improvement is defined as an absolute ES of 0 or 1 po int (excluding friability) from mMS and an absolute Robarts Histopathology Index (RHI) score of ≤3 points with no lamina propria neutrophils, no neutrophils in epithelium, no erosion or ulceration. e Corticosteroid-free remission is defined as being in clinical remission by mMS in addition to not requiring any treatment with corticosteroid for at least 8 weeks at Week 54, among the patients who used oral cotricosteroids at baseline. f p < 0.05 The relationship between histologic-endoscopic mucosal improvement at Week 54 and disease progression and longer-term outcomes after Week 54 was not evaluated in UC Trial I. 14.2 Adult Crohn's Disease The safety and efficacy of ZYMFENTRA were assessed in a randomized, double-blind, placebo-controlled clinical studies (CD Trial I; NCT03945019 ) in adult subjects with moderately to severely active CD, defined as Crohn's Disease Activity Index (CDAI) score of 220 to 450 points, and a centrally-reveiwed Simplified Endoscopic Activity Score for Crohn’s Disease (SES-CD) of ≥6 points for ileal-colonic CD (or ≥4 points for isolated ileal disease). Subjects had demonstrated an inadequate response or intolerance to treatment with corticosteroids and/or immunosuppressants. Subjects were permitted to use stable doses of oral amisosalicylates, oral corticosteroids (prednisone ≤20 mg/day or equivalent, budesonide ≤9 mg/day), CD-related antibiotics and/or immunomodulatory agents (azathioprine, 6-mercaptopurine, or methotrexate). Corticosteroid dose was tapered after Week 10. All subjects received three intravenous induction doses of 5 mg/kg infliximab-dyyb at Week 0, 2 and 6. In order to be ranomized to treatment in CD Trial I, subjects had to be in clinical response at Week 10. Clinical response was defined as a decrease from baseline in CDAI of at least 100 points (i.e., CDAI-100 responders). A total of 323 subjects were randomized at Week 10 in a double-blind fashion (2:1) to ZYMFENTRA 120 mg as a subcutaneous injection or placebo every 2 weeks. At the time of randomization into the double-blind phase (Week 10), 61% were receiving aminosalicylates, 40 % were receiving oral corticosteroids, and 32% were receiving immunomodulators including azathioprine, 6-mercaptopurine, or methotrexate. A total of 11% of randomized subjects had prior exposure to biological products. Subjects in the double-blind phase had a mean age of 35 years (range 18 to 75 years); 40% were female; and 91% identified as White, 4% identified as American Indian or Alaska Native, 4% identified as Asian, 0.3% as Black or African American, and 1% identified as another racial group. The co-primary endopoints were clinical remission (based on CDAI) and endoscopic response at Week 54. Secondary endpoints included endoscopic remission, and corticosteroid-free remission at Week 54 (see Table 4 ). Table 4: Proportion of Subjects with Crohn's Disease Meeting Efficacy Endpoints at Week 54 in CD Trial I Endpoint ZYMFENTRA Placebo Treatment Difference a and 95% CI Clinical Remission (Based on CDAI) b at Week 54 Total population N=216 63% N=107 30% 35% c (24, 45) No prior biological product expousre N=191 62% N=98 31% Prior biological product exposure N=25 72% N=9 22% Endoscopic Response d at Week 54 Total population N=216 50% N=107 18% 34% c (23, 43) No prior biological product exposure N=191 51% N=98 17% Prior biological product exposure N=25 48% N=9 22% Enoscopic Remission e at Week 54 Total population N=216 35% N=107 10% 25% c (16, 33) No prior biological product exposure N=191 35% N=98 10% Prior biological product exposure N=25 36% N=9 11% Corticosteroid-free Remission f at Week 54 Total population N=92 40% N=43 21% 19% g No prior biological product expousre N=81 35% N=40 23% Prior biological product exposure N=11 82% N=3 0% CI=confidence interval, CDAI=Crohn's Disease Activity Index a Treatment difference (adjusted for stratification factors of previous exposure to biological product, use of treatment with oral corticosteroids at Week 0, and clinical remission status at Week 10). b Clinical remission (based on CDAI) is defined as an absolute CDAI score of <150 points. c p < 0.0001. d Endoscopic response is defined as a >50% decrease in SES-CD from the baseline value. e Endoscopic remission is defined as an absolute SES-CD score of ≤4 with no sub-score of >1. f Corticosteroid-free remission is defined as being in clinical remission in addition to not receiving any corticosteroid for at least 8 weeks prior to Week 54, among the subjects who used oral corticosteroids at baseline. g p < 0.05

8.5 Geriatirc Use Clinical trials of ZYMFENTRA did not include sufficient numbers of subjects aged 65 and over (8 subjects with UC and 6 subjects with CD) to determined whether they respond differently from younger subjects.

8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established.

8.1 Pregnancy Risk Summary Available data from reports of pregnancy in clinical trials with ZYMFENTRA are insufficient to identify a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with inflammatory bowel disease in pregnancy ( see Clinical Considerations ). Available observational data in pregnant women exposed to infliximab products administered intravenously showed no increased risk of major malformations among live births as compared to those exposed to non-biologics. Most TNF blockers, such as infliximab products, administered intravenously are transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. Infants exposed in utero should not be administered live vaccines for at least 6 months after birth ( see Clinical Considerations ). Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with ZYMFENTRA. The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Consideration Disease-Associated Maternal and/or Embryo/Fetal Risk Published data suggest that there is an increased risk of adverse pregnancy outcomes in women with inflammatory bowel disease associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2.5 kg) and small for gestational age at birth. Fetal/Neonatal Adverse Reactions The risk of fetal/neonatal adverse reactions with in utero exposure to infliximab-dyyb administered subcutaneously is unknown. However, most TNF blockers, such as infliximab products, cross the placenta and have been detected in infant serum up to 6 months following birth. Consequently, infants exposed to infliximab products may be at increased risk of infection, including disseminated infection which can become fatal. At least a six-month waiting period following birth is recommended before the administration of live vaccines (e.g., BCG vaccine or other live vaccines, such as the rotavirus vaccine) to infants exposed to intravenous infliximab in utero [ see Warnings and Precautions (5.12) ]. Cases of agranulocytosis in infants exposed to intravenous infliximab in utero have also been reported. Therefore, ZYMFENTRA, administered during pregnancy may affect immune responses in the in utero -exposed newborn and infant [ see Adverse Reactions 6.2 ]. Data Animal Data Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with ZYMFENTRA.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available data from reports of pregnancy in clinical trials with ZYMFENTRA are insufficient to identify a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with inflammatory bowel disease in pregnancy ( see Clinical Considerations ). Available observational data in pregnant women exposed to infliximab products administered intravenously showed no increased risk of major malformations among live births as compared to those exposed to non-biologics. Most TNF blockers, such as infliximab products, administered intravenously are transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. Infants exposed in utero should not be administered live vaccines for at least 6 months after birth ( see Clinical Considerations ). Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with ZYMFENTRA. The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Consideration Disease-Associated Maternal and/or Embryo/Fetal Risk Published data suggest that there is an increased risk of adverse pregnancy outcomes in women with inflammatory bowel disease associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2.5 kg) and small for gestational age at birth. Fetal/Neonatal Adverse Reactions The risk of fetal/neonatal adverse reactions with in utero exposure to infliximab-dyyb administered subcutaneously is unknown. However, most TNF blockers, such as infliximab products, cross the placenta and have been detected in infant serum up to 6 months following birth. Consequently, infants exposed to infliximab products may be at increased risk of infection, including disseminated infection which can become fatal. At least a six-month waiting period following birth is recommended before the administration of live vaccines (e.g., BCG vaccine or other live vaccines, such as the rotavirus vaccine) to infants exposed to intravenous infliximab in utero [ see Warnings and Precautions (5.12) ]. Cases of agranulocytosis in infants exposed to intravenous infliximab in utero have also been reported. Therefore, ZYMFENTRA, administered during pregnancy may affect immune responses in the in utero -exposed newborn and infant [ see Adverse Reactions 6.2 ]. Data Animal Data Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with ZYMFENTRA. 8.2 Lactation Risk Summary There are no data on the presence of infliximab-dyyb or its metabolites in either human or animal milk, the effects on the breastfed infant, or the effects on milk production after subcutaneous administration. Published literature show that infliximab is present at low levels in human milk after intravenous administration. Systemic exposure in a breastfed infant is expected to be low because infliximab products are largely degraded in the gastrointestinal tract. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZYMFNETRA and any potential adverse effects on the brestfed child from ZYMFENTRA or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established. 8.5 Geriatirc Use Clinical trials of ZYMFENTRA did not include sufficient numbers of subjects aged 65 and over (8 subjects with UC and 6 subjects with CD) to determined whether they respond differently from younger subjects.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ZYMFENTRA (Infliximab-dyyb) injection for subcutaneous use is supplied as a sterile, preservative-free, clear to opalescent, colorless to pale brown solution in a single-use prefilled syringe, prefilled syringe with needle guard or prefilled pen. The syringe is fitted with a needle shield which are not made with natural rubber latex or any derivatives from natural rubber latex in any ingredient. Prefilled Syringe Each prefilled syringe is equipped with a 29 gauge fixed 1/2 inch needle with a rigid needle shield and a plunger stopper. The following configurations are available: 1 prefilled syringe (120 mg/mL solution) with 2 alcohol pads. (NDC: 72606-025-05) 2 prefilled syringes (120 mg/mL solution) with 2 alcohol pads. (NDC: 72606-025-06) 4 prefilled syringes (120 mg/mL solution) with 4 alcohol pads. (NDC: 72606-025-07) 6 prefilled syringes (120 mg/mL solution) with 6 alcohol pads. (NDC: 72606-025-08) Prefilled Syringe with Needle Guard Each prefilled syringe is equipped with a 29 gauge fixed 1/2 inch needle with a rigid needle shield and an automatic needle guard, and a plunger stopper. The following configurations are available: 1 prefilled syringe with needle guard (120 mg/mL solution) with 2 alcohol pads. (NDC: 72606-025-09) 2 prefilled syringes with needle guard (120 mg/mL solution) with 2 alcohol pads. (NDC: 72606-025-10) 4 prefilled syringes with needle guard (120 mg/mL solution) with 4 alcohol pads. (NDC: 72606-025-11) 6 prefilled syringes with needle guard (120 mg/mL solution) with 6 alcohol pads. (NDC: 72606-025-12) Prefilled Pen Each prefilled pen is equipped with a 27 gauge fixed 1/2 inch needle with a rigid needle shield and a plunger stopper. The following configurations are available: 1 prefilled pen (120 mg/mL solution) with 2 alcohol pads. (NDC: 72606-025-01) 2 prefilled pens (120 mg/mL solution with 2 alcohol pads. (NDC: 72606-025-02) 4 prefilled pens (120 mg/mL solution) with 4 alcohol pads. (NDC: 72606-025-03) 6 prefilled pens (120 mg/mL solution) with 6 alcohol pads. (NDC: 72606-025-04) Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE. Keep the product in its outer carton until time of administration in order to protect from light. If needed, the product may be stored at room temperature at 20°C to 25°C (68°F to 77°F) for up to 14 days with protection from light. Once the product has been stored at room temperature, it should not be placed back into the refrigerator. The product must be discarded if not used within the 14 days.

WARNING: SERIOUS INFECTIONS and MALIGNANCY See full prescribing information for complete boxed warning Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as hitoplasmosis) and infections due to other opportunistic pathogens. ( 5.1 ) Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis. ( 5.1 ) Perform test for latent TB; if positive, start treatment for TB prior to starting ZYMFENTRA. Monitor all patients for active TB during treatment, even if initial latent TB test is negative. ( 5.1 ) Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including infliximab products. ( 5.2 ) Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers including infliximab products. Almost all had received azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. The majority of cases were reported in patients with Crohn's disease or ulcerative colitis, most of whom were adolescent or young adult males. ( 5.2 ) SERIOUS INFECTIONS Patients treated with TNF blockers, inculding ZYMFENTRA, are at increased risk for developing serious infections that may lead to hospitalization or death [ see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 ) ]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Test patientsfor latent tuberculosis before ZYMFENTRA use and during therapy. Initiate treatment for latent infection prior to ZYMFENTRA use. Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria. Carefully consider the risks and benefits of treatment with ZYMFENTRA prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symtoms of infection during and after treatment with ZYMFENTRA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including infliximab products [ see Warnings and Precautions ( 5.2 ) ]. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. Almost all patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. The majority of reported cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were in young adult males. [ see Use in Specific Population ( 8.4 ) ].