Celltrion

STEQEYMA (CT-P43) is approved for both adult and pediatric patients with plaque psoriasis (PsO) and active psoriatic arthritis (PsA) as well as adults with Crohn's disease (CD) and ulcerative colitis (UC)STEQEYMA is a strategic addition to Celltrion's portfolio, expanding the portfolio and building on Celltrion's expertise in immunologySTEQEYMA is expected to be marketed in the U.S. in February 2025 JERSEY CITY, N.J., Dec. 17, 2024 -- Celltrion announced today that the U.S. Food and Drug Administration (FDA) has approved STEQEYMA® (ustekinumab-stba), a biosimilar to STELARA® (ustekinumab), for subcutaneous injection or intravenous infusion in adult and pediatric patients with plaque psoriasis and psoriatic arthritis, as well as adult patients with Crohn's disease and ulcerative colitis.[1] The FDA approval of STEQEYMA was based on the totality of evidence, including the results from a phase III study in adults with moderate to severe plaque psoriasis, in which the primary endpoint was the rate of change in the Psoriasis Area and Severity Index (PASI) for skin symptoms. The clinical results demonstrated that STEQEYMA and its reference product, ustekinumab, are highly similar, and have no clinically meaningful differences in terms of safety and efficacy. "The approval of STEQEYMA reflects Celltrion's continued investment in providing treatment options to patients diagnosed with ulcerative colitis, Crohn's disease, psoriasis, and psoriatic arthritis," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA. "STEQEYMA is now the latest biologic in our immunology portfolio, joining ZYMFENTRA® (infliximab-dyyb). Our portfolio, supported by our fully integrated platform, establishes Celltrion USA as an important player in the U.S. immunology market." "Plaque psoriasis and psoriatic arthritis are both autoimmune disorders that affect the skin and present differently in all patients," said Mark G. Lebwohl*, MD, Icahn School of Medicine at Mount Sinai, New York. "The approval of new treatment option is welcome news for people living with certain chronic inflammatory conditions, such as psoriasis, which affect more than 3% of the US adult population." Ustekinumab is a fully human monoclonal antibody that selectively inhibits both interleukin (IL)-12 and IL-23, two cytokines that play an important role in inflammatory and immune responses. Celltrion Inc. had reached a settlement and license agreement with the manufacturer of the reference biologic, Johnson & Johnson, granting a license entry date for STEQEYMA in the United States in February 2025. Notes to Editors:*Dr. Mark Lebwohl is a paid consultant for Celltrion. About STEQEYMA® (ustekinumab-stba)STEQEYMA®, formerly known as CT-P43, is a human IL-12 and -23 antagonist indicated for multiple immune-mediated diseases. It encompasses all indications approved for the STELARA® reference product, including psoriasis (PsO), psoriatic arthritis (PsA), Crohn's disease (CD), ulcerative colitis (UC) in adults, and PsO and PsA in pediatric patients 6 years of age and older. STEQEYMA is available in both subcutaneous and intravenous formulations. The subcutaneous injection comes in two strengths: 45mg/0.5 mL or 90mg/1 mL solution in a single-dose, prefilled syringe. The intravenous infusion is provided as a 130mg/26 mL (5mg/mL) solution in a single-dose vial. INDICATIONSSTEQEYMA® (ustekinumab-stba) is indicated for the treatment of:Plaque Psoriasis (PsO) in adults and pediatric patients 6 years of age and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.Psoriatic Arthritis (PsA) in adults and pediatric patients 6 years of age and older with active psoriatic arthritis.Crohn's Disease (CD) in adult patients with moderately to severely active Crohn's disease.Ulcerative Colitis (UC) in adult patients with moderately to severely active ulcerative colitis. IMPORTANT SAFETY INFORMATIONSTEQEYMA is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in STEQEYMASerious infections have occurred. Avoid starting STEQEYMA during any clinically important active infection. If a serious or clinically significant infection develop, discontinue STEQEYMA until the infection resolves.Serious infections from mycobacteria, salmonella, and BCG vaccinations have been reported in patients genetically deficient in IL-12/IL-23. Consider diagnostic tests for these infections as dictated by clinical circumstances.Evaluate patients for TB prior to starting STEQEYMA. Initiate treatment of latent TB before administering STEQEYMA.Ustekinumab products may increase risk of malignancy. The safety of ustekinumab products in patients with a history of or a known malignancy has not been evaluated. Monitor all patients receiving STEQEYMA for signs of malignancies.If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue STEQEYMA.If Posterior Reversible Encephalopathy Syndrome (PRES) is suspected, treat promptly, and discontinue STEQEYMA.Avoid use of live vaccines in patients during treatment with STEQEYMA. Non-live vaccinations received during STEQEYMA treatment may not elicit enough immune response to prevent disease.If diagnosis of noninfectious pneumonia is confirmed, discontinue STEQEYMA and institute appropriate treatment.The most common adverse reactions (≥3%) reported in patients receiving ustekinumab were:Psoriasis: nasopharyngitis, upper respiratory tract infection, headache, and fatigue.CD: vomiting, nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis.UC: nasopharyngitis, nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea. For more information, see Full Prescribing Information. About ZYMFENTRA® (infliximab-dyyb)ZYMFENTRA® is a prescription medicine used as an injection under 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). ZYMFENTRA blocks the action of tumor necrosis factor-alpha (TNF-alpha), a protein that can be overproduced in response to certain diseases and cause the immune system to attack normal, healthy parts of the body.ZYMFENTRA (infliximab-dyyb) was approved by the FDA through the Biologics License Application (BLA) under the 351 (a) pathway of the Public Health Service Act (a "stand-alone" BLA). ZYMFENTRA is considered a new biologic with a first-approved subcutaneous administration form and thus will be under patent protection for its dosage form by 2037 and for its route of administration by 2040. ZYMFENTRA (infliximab-dyyb) U.S. Use and Important Safety InformationZYMFENTRA is a prescription medicine indicated in adults for maintenance treatment of:moderately to severely active Crohn's disease following treatment with an infliximab product administered intravenously.moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously. It is not known if ZYMFENTRA is safe and effective in children under 18 years of age. What is the most important information I should know about ZYMFENTRA? SERIOUS INFECTIONSPatients treated with ZYMFENTRA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis. Reported infections include:Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with ZYMFENTRA. Treatment for latent infection should be initiated prior to treatment with ZYMFENTRA.Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered 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. The risks and benefits of treatment with ZYMFENTRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with ZYMFENTRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Risk of infection may be higher in patients greater than 65 years of age, patients with comorbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab included arthritis bacterial, pneumonia, and urinary tract infection. MALIGNANCIESMalignancies, some fatal, have been reported in children, adolescents, and young adults treated with TNF blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants. Post-marketing cases of hepatosplenic T-cell lymphoma, 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. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis, and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with ZYMFENTRA, especially in these patient types. In clinical trials of all TNF blockers, more cases of malignancies were observed compared with controls and the expected rate in the general population. In clinical trials of some TNF blockers, including infliximab products, more cases of other malignancies were observed compared with controls. As the potential role of TNF blocker therapy in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy.Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. CONTRAINDICATIONSZYMFENTRA is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients of ZYMFENTRA or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness). HEPATITIS B VIRUS REACTIVATIONTNF blockers, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating ZYMFENTRA. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing ZYMFENTRA for patients identified as carriers of HBV, and monitor closely for active HBV infection during and following termination of therapy with ZYMFENTRA. Discontinue ZYMFENTRA in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of ZYMFENTRA, and monitor patients closely. HEPATOTOXICITYHepatobiliary disorders, including acute liver failure, jaundice abnormal hepatic function, hepatic steatosis, hepatitis, hepatotoxicity, hyperbilirubinemia, and non-alcoholic fatty liver, have been reported in patients receiving infliximab products post-marketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, ZYMFENTRA should be discontinued, and a thorough investigation of the abnormality should be undertaken. CONGESTIVE HEART FAILURECases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Some cases had a fatal outcome. In several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. ZYMFENTRA has not been studied in patients with a history of CHF and ZYMFENTRA should be used with caution in patients with CHF. HEMATOLOGIC REACTIONCases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to infliximab-product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of ZYMFENTRA in patients who develop significant hematologic abnormalities. HYPERSENSITIVITY AND OTHER ADMINISTRATION REACTIONSIn post-marketing experience, serious systemic hypersensitivity reactions (including anaphylaxis, hypotension, and serum sickness) have been reported following administration of infliximab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. INJECTION SITE REACTIONSIn clinical studies, localized injection-site reactions were reported following administration of ZYMFENTRA. If a clinically significant injection-site reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. NEUROLOGIC REACTIONSAgents that inhibit TNF have been associated with central nervous system (CNS) manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering ZYMFENTRA in patients with these disorders and consider discontinuation if these disorders develop. RISK OF INFECTION WITH CONCURRENT ADMINISTRATION OF OTHER BIOLOGICS PRODUCTSSerious infections and neutropenia have been reported with concurrent use of ZYMFENTRA with other immunosuppressive biological products. 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. RISK OF ADDITIVE IMMUNOSUPPRESSIVE EFFECTS FROM PRIOR BIOLOGICAL PRODUCTSConsider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA. AUTOIMMUNITYTreatment with TNF blockers may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue ZYMFENTRA treatment if symptoms of a lupus-like syndrome develop. VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTSPrior to initiating ZYMFENTRA, update vaccinations in accordance with current vaccination guidelines. Live vaccines or therapeutic infectious agents should not be given with ZYMFENTRA due to the possibility of clinical infections, including disseminated infections. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to ZYMFENTRA. ADVERSE REACTIONSIn clinical trials with ZYMFENTRA, the most common adverse reactions occurring in ≥3% of ZYMFENTRA-treated patients included site reactions, COVID-19, anemia, arthralgia, infection site reaction, increased alanine aminotransferase and abdominal pain for UC, and 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 for CD. This is the most important information to know about ZYMFENTRA. For more information, talk to your HCP.  Please click for Full U.S. Prescribing Information.Globally, prescribing information varies; refer to the individual country product label for complete information. About Celltrion USACelltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence, and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. Celltrion endeavors to offer high-quality, cost-effective solutions through an extensive global network that spans more than 110 countries. For more information, please visit: www.celltrionusa.com. FORWARD-LOOKING STATEMENTCertain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion that may constitute forward-looking statements, under pertinent securities laws. These statements may be identified by words such as "prepares," "hopes to," "upcoming," "plans to," "aims to," "to be launched," "is preparing," "once gained," "could," "with the aim of," "may," "once identified," "will," "working towards," "is due," "become available," "has potential to," the negative of these words or such other variations thereon or comparable terminology.In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion's management, of which many are beyond its control. Forward-looking statements are provided to allow potential investors the opportunity to understand management's beliefs and opinions with respect to the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them. Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or results expressed or implied by such forward-looking statements. Such risks and uncertainties may include, among other things, uncertainties regarding the launch timing and commercial success of Celltrion in the United States; the uncertainties inherent in supply chain, manufacturing, research and development, and the possibility of unfavorable new clinical data and further analyses of existing clinical data as they relate to Celltrion products; intellectual property and/or litigation/settlement implications; decisions by the FDA impacting labeling, manufacturing processes, safety, promotion, and/or other matters that could affect the availability or commercial potential of Celltrion products; and uncertainties regarding access challenges for our biosimilar products where our product may not receive appropriate formulary access or remains in a disadvantaged position relative to competitive products; and competitive developments. A further description of risks and uncertainties can be found in Celltrion's Annual Report. Although forward-looking statements contained in this presentation are based upon what management of Celltrion believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Celltrion undertakes no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements. TrademarksSTELARA® is a registered trademark of Johnson & Johnson.STEQEYMA® is a registered trademark of Celltrion, Inc., used under license.References[1] STEQEYMA U.S. prescribing information (2024)

The Committee for Medicinal Products for Human Use (CHMP) adopts positive opinions for Celltrion’s three biosimilar candidates – Eydenzelt® (aflibercept), Stoboclo® and Osenvelt® (denosumab), and Avtozma® (tocilizumab)Celltrion is committed to expanding access to biologic treatments in skeletal-related disorders, ophthalmology, and immunology December 16, 2024 08:33 AM Japan Standard Time INCHEON, South Korea -- Celltrion today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted positive opinions and recommended marketing authorisations for three biosimilar candidates: Eydenzelt® (CT-P42, aflibercept), Stoboclo® and Osenvelt® (CT-P41, denosumab), and Avtozma® (CT-P47, tocilizumab). This significant milestone reflects the company’s leadership in biosimilar innovation and commitment to expanding access to biologic treatments across Europe. Eydenzelt (40 mg/mL solution for injection in vial and pre-filled syringe), a biosimilar to Eylea® (aflibercept), is recommended for approval to treat multiple retinal disorders, including neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO, branch RVO or central RVO), diabetic macular edema (DME) and myopic choroidal neovascularisation (myopic CNV). In a Phase III study of Eydenzelt, the efficacy, safety, pharmacokinetics and immunogenicity of Eydenzelt was compared to Eylea in patients with diabetic macular edema (DME), demonstrating therapeutic equivalence to Eylea by meeting the predefined equivalence criteria.1 If marketing authorisation is granted by the European Commission (EC), Eydenzelt would be one of the first-wave aflibercept biosimilars in Europe. Stoboclo (60 mg solution for injection in pre-filled syringe) and Osenvelt (120 mg solution for injection in vial) have been recommended for approval for all indications of the reference products Prolia® and Xgeva®, respectively. The positive CHMP opinion was based on the totality of evidence including results from a Phase III clinical trial in postmenopausal osteoporosis (PMO), and the results showed that CT-P41 had equivalent efficacy and pharmacodynamics (PD) to reference denosumab, with similar pharmacokinetics (PK) and comparable safety and immunogenicity profiles.2 Avtozma, a biosimilar referencing RoActemra® (tocilizumab), has been recommended for all indications of its reference product, including moderate to severely active rheumatoid arthritis (RA), active systemic juvenile idiopathic arthritis (sJIA), juvenile idiopathic polyarthritis (pJIA) and giant cell arteritis (GCA). The positive CHMP opinion for Avtozma was supported by a comprehensive data package and totality of evidence demonstrating Avtozma’s biosimilarity to RoActemra, with no clinically meaningful differences in efficacy, PK equivalence, safety or immunogenicity.3,4 “With CHMP approvals for Eydenzelt, Avtozma, and Prolia/Xgeva biosimilars, Celltrion solidifies its leadership in the European biosimilar market, offering one of the most extensive antibody biosimilar portfolios. Our vertically integrated model ensures supply chain stability while addressing the specific challenges faced by European healthcare professionals and patients. These approvals underscore our commitment to supporting European healthcare systems by improving access to high-quality, affordable treatments,” said Taehun Ha, Vice President and Head of Europe. “Our focus remains on empowering clinicians with the tools and solutions they need, as we aim to transition from a pioneer to a frontier leader in European healthcare.” The CHMP’s recommendations will now be referred to the EC, which will decide whether to grant a marketing authorisation for Eydenzelt, Stoboclo and Osenvelt, and Avtozma. If marketing authorisations are granted, the three biosimilars will be made available across EU member states, furthering Celltrion’s commitment to delivering innovative and accessible healthcare solutions. About CT-P41 Phase III Clinical TrialThe Phase III study randomised 479 patients to receive 60 mg of CT-P41 or reference product every six months (Weeks 0 and 26; treatment period [TP] I). Before dosing at Week 52, patients initially assigned to reference product in TP I were re-randomised in a 1:1 ratio to continue with the reference product or switch to CT-P41 in TP. All patients initially randomly assigned to CT-P41 in TP I continued their treatment with CT-P41 in TP II. In TP II, 422 patients were randomised in Week 52 (CT-P41 maintenance group: 221, reference product maintenance group: 100, switched to CT-P41 group: 101). The primary efficacy endpoint was met in terms of percent change from baseline in bone mineral density (BMD) for lumbar spine (L1-L4) by dual-energy X-ray absorptiometry (DXA) at Week 52, and the primary pharmacodynamics (PD) endpoint was met in terms of area under the effect curve (AUEC) of serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) over the initial six months. Results of the study showed that CT-P41 had equivalent efficacy and PD to reference denosumab, with similar PK and comparable safety and immunogenicity profiles.2 About CT-P42 Phase III Clinical TrialIn a randomised, double-masked, parallel-group, multi-centre Phase III study of Eydenzelt® (CT-P42), the efficacy, safety, pharmacokinetics, usability and immunogenicity of Eydenzelt was compared to Eylea® (aflibercept) in patients with diabetic macular edema (DME). The primary endpoint was the change from baseline in best corrected visual acuity (BCVA) measured at Week 8, comparing Eydenzelt and Eylea. Results of the study showed that Eydenzelt met the predefined equivalence criteria, and secondary endpoints of efficacy, safety, and immunogenicity also showed trends similar to Eylea.1,5 About CT-P47 Phase III Clinical TrialThis was a Phase III, randomised, active-controlled, double-blind trial to compare the efficacy and safety of Avtozma® (CT-P47) and RoAtemra® (tocilizumab) in patients with moderate to severely active rheumatoid arthritis (RA). The Phase III study randomised 479 patients to receive 8mg/kg of CT-P47 or reference tocilizumab every 4 weeks (Week 0 and 24; treatment period [TP] I). Before dosing at Week 24, patients initially assigned to tocilizumab in TP I were re-randomised in a 1:1 ratio to continue with tocilizumab or switch to CT-P47 in TP II up to Week 52. In TP II, 444 patients were randomised in Week 24 (CT-P47 maintenance group: 225, tocilizumab maintenance group: 109, switched to CT-P47 group: 110). The primary endpoint was mean change from baseline in Disease Activity score in 28 joints (DAS28; erythrocyte sedimentation rate [ESR]) at week 12. Efficacy equivalence was determined if confidence intervals (CIs) for the treatment difference was within the predefined equivalence margin: (95% CI: -0.6, +0.6 (analysis of covariance [ANCOVA]) at week 12). Therapeutic equivalence of CT-P47 and reference tocilizumab in treating RA was demonstrated and supported by comparable and sustained efficacy results up to Week 52. CT-P47 was also well tolerated with a safety profile comparable to reference tocilizumab, and no notable safety issue was identified following the single transition from reference tocilizumab to CT-P47 compared with maintenance groups up to Week 52. 3,4 About Stoboclo® (CT-P41, biosimilar candidate of denosumab)Stoboclo® (denosumab), a receptor activator of NF-κb ligand (RANKL) inhibitor, is a treatment developed as a biosimilar to reference product Prolia® (denosumab). In Europe, Stoboclo has been recommended for approval to treat osteoporosis in postmenopausal women and in men at increased risk of fractures, bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures, and bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture. About Osenvelt® (CT-P41, biosimilar candidate of denosumab)Osenvelt® (denosumab) is a receptor activator of NF-κb ligand (RANKL) inhibitor developed as a biosimilar referencing Xgeva® (denosumab). Osenvelt has been recommended for approval in Europe to prevent skeletal-related events in adults with advanced malignancies involving bone, and to treat adults and skeletally mature adolescents with giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity. About Eydenzelt® (CT-P42, biosimilar candidate of aflibercept)Eydenzelt® (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor referencing Eylea®. Based on comprehensive data from a Phase III clinical trial confirming therapeutic equivalence to Eylea1, Eydenzelt was filed for regulatory approval with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in June and November 2023, respectively. About Avtozma® (CT-P47, biosimilar candidate of tocilizumab)CT-P47, containing the active ingredient tocilizumab, is a recombinant humanised monoclonal antibody that acts as an interleukin 6 (IL-6) receptor antagonist. Based on data from the global Phase III clinical trial, designed to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of CT-P47 compared to the reference product RoActemra®4, CT-P47 was filed for regulatory approval with the U.S. FDA and EMA in January and February 2024, respectively. About CelltrionCelltrion is a leading biopharmaceutical company based in Incheon, South Korea that specialises in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. The company’s solutions include world-class monoclonal antibody biosimilars such as Remsima®, Truxima® and Herzuma®, providing broader patient access globally. Celltrion has also received U.S. FDA and EC approval for Vegzelma® and Yuflyma®, FDA approval for Zymfentra®, and EC approval for Remsima® SC, Omlyclo®, SteQeyma®. To learn more, please visit www.celltrion.com/en-us. FORWARD-LOOKING STATEMENTCertain information set forth in this press release contains statements related to our future business, and financial performance and future events or developments involving Celltrion Inc. and its subsidiaries that may constitute forward-looking statements, under pertinent securities laws.These statements may be identified by words such as “prepares,” “hopes to,” “upcoming,” ”plans to,” “aims to,” “to be launched,” “is preparing,” “once gained,” “could,” “with the aim of,” “may,” “once identified,” “will,” “working towards,” “is due,” “become available,” “has potential to,” the negative of these words or such other variations thereon or comparable terminology.In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion Inc. and its subsidiaries' management, of which many are beyond its control.Forward-looking statements are provided to allow potential investors the opportunity to understand management’s beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them.Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or results expressed or implied by such forward-looking statements.Celltrion Inc. and its subsidiaries undertake no obligation to update forward-looking statements if circumstances or management’s estimates or opinions should change except as required by applicable securities laws. TrademarkStoboclo® and Osenvelt® are registered trademarks of Celltrion Inc. Prolia® and Xgeva® are registered trademarks of Amgen Inc.Eydenzelt® is a registered trademark of Celltrion Inc. Eylea® is a registered trademark of Bayer AG.Avtozma® is a registered trademark of Celltrion, Inc., used under license. RoActemra® is a registered trademark of Chugai Pharmaceutical Co., Ltd. References1 Sebastian Wolf et al., Long-term efficacy and Safety of CT-P42 compared to Reference Aflibercept in Diabetic Macular Edema: 52-Week Results from the Phase 3 CT-P42 3.1. [EURETINA 2024, Abstract #CA24-2257-8397]. Available at: https://abstracts.euretina.org/2024/ca24-2257-8397/r/recxUD7DqYfFfjC7s [Last accessed December 2024]. 2 Reginster JY et al. Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis. Osteoporos Int. 2024 Nov;35(11):1919-1930. doi: 10.1007/s00198-024-07161-x. Epub 2024 Jul 23. PMID: 39042292; PMCID: PMC11499533. Available at: https://pubmed.ncbi.nlm.nih.gov/39042292/ [Last accessed December 2024]. 3 Smolen JS et al., Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47. RMD Open. 2024;10(4), e004514. Available at: https://rmdopen.bmj.com/content/10/4/e004514.abstract [Last accessed December 2024]. 4 Gerd Burmester et al., Similar Efficacy, PK, Safety, and Immunogenicity of Tocilizumab Biosimilar (CT-P47) and Reference Tocilizumab in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: Week 52 Results from the Phase III Single Transition Study. Poster Presentation (abstract no. 0502). Presented at ACR 2024. Available at: https://acrabstracts.org/abstract/similar-efficacy-pk-safety-and-immunogenicity-of-tocilizumab-biosimilar-ct-p47-and-reference-tocilizumab-in-patients-with-moderate-to-severe-active-rheumatoid-arthritis-week-52-results-from-the/ [Last accessed December 2024]. 5 Sebastian Wolf et al., Biosimilar Candidate CT-P42 in Diabetic Macular Edema: 24-Week Results from a Randomized, Active-Controlled, Phase III Study. Available at: https://www.sciencedirect.com/science/article/pii/S2468653024003063 [Last accessed December 2024].

78-Week results from Phase III randomized controlled trial (RCT) including switching data from reference denosumab to CT-P41 (biosimilar candidate of denosumab) demonstrate comparable efficacy and safety results; Results support the therapeutic equivalence of CT-P41 and reference denosumab in treating postmenopausal women with osteoporosis (PMO)[1] Data from the Phase III RCT showed comparable and sustained efficacy, safety and immunogenicity profile to the reference tocilizumab in patients with active moderate-to-severe rheumatoid arthritis (RA) over 1-year after single transition from Week 24[2] JERSEY CITY, N.J., Nov. 18, 2024 /PRNewswire/ -- Celltrion today presented additional data from a Phase III randomized controlled trial (RCT) for CT-P41, a biosimilar candidate referencing PROLIA®/XGEVA® (denosumab) in postmenopausal women with osteoporosis (PMO) and a Phase III RCT for CT-P47, a biosimilar candidate referencing ACTEMRA® (tocilizumab) in patients with moderate-to-severe active rheumatoid arthritis (RA) at the American College of Rheumatology (ACR) Convergence 2024 in Washington, D.C. The additional efficacy and safety results from Week 52 to Week 78 including switching data from reference denosumab to the CT-P41 (Treatment Period [TP] II) showed comparable and sustained efficacy results to reference denosumab in treating women with PMO after the single transition from reference denosumab to CT-P41. CT-P41 was well tolerated with a safety profile comparable to reference denosumab, and no notable safety issue was identified following the single transition compared with maintenance groups up to Week 78. The results further support the biosimilarity between CT-P41 and reference denosumab in treating women with PMO.[1] In addition, post-hoc impact analysis using data from the Phase III RCT was conducted to determine any correlation between immunogenicity and clinical outcomes in PMO between the treatment groups. According to the results, the impact of anti-drug antibody (ADA) on pharmacokinetics (PK), efficacy and safety and the treatment emergent adverse events (TEAE) incidences were comparable between the treatment groups in the ADA status groups.[3] Despite the high ADA incidence compared to the reference denosumab historical studies,[4] it can be suggested that ADA to CT-P41 and reference denosumab has no clinical impact considering the high sensitivity and specificity of the assay and further evaluation of immunogenicity impact. "We are excited to announce the additional evidence from the RCT that further supports the biosimilarity between CT-P41 and reference denosumab in treating PMO," said Hetal Patel, PharmD, MBA, Head of Medical Affairs at Celltrion USA. "These results further underline the capabilities of our dedicated biosimilar platform and anticipated diversification of our portfolio." Results of the single transition from the reference tocilizumab to CT-P47 from a Phase III RCT were also presented at the ACR. The 1-year results showed that CT-P47 had comparable and sustained efficacy, safety and immunogenicity profiles in patients with active moderate-to-severe rheumatoid arthritis (RA) compared to the reference tocilizumab even after switching. These data further support biosimilarity of CT-P47.[2] "Biosimilars offer cost savings and health gains for our patients and play an important role in treating rheumatic diseases," said Prof. Gerd-Rüdiger Burmester, MD, Professor of Medicine and Rheumatology, Senior Professor in the Department of Rheumatology and Clinical Immunology at Charité - Universitätsmedizin Berlin, Germany. "The RCT data of CT-P47 presented at ACR further establish the comparable safety and efficacy of biosimilars to their reference products." About CelltrionCelltrion is a leading biopharmaceutical company based in Incheon, South Korea that specializes in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. Celltrion currently has five biosimilars approved by the U.S. FDA: INFLECTRA® (infliximab-dyyb), TRUXIMA® (rituximab-abbs), HERZUMA® (trastuzumab-pkrb), VEGZELMA® (bevacizumab-adcd) and YUFLYMA®(adalimumab-aaty) as well as a novel biologic ZYMFENTRA®. About Celltrion USACelltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. For more information, please visit: www.celltrionusa.com. About CT-P41 (biosimilar candidate of denosumab)CT-P41 is a proposed biosimilar of reference denosumab, a fully human monoclonal antibody that binds the cytokine receptor activator of NF-κb ligand (RANKL). Based on data from the Phase III clinical trial designed to evaluate the efficacy, safety, and immunogenicity of CT-P41 compared to the reference denosumab, CT-P41 was filed for regulatory approval with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in November 2023 and March 2024, respectively. About CT-P47 (biosimilar candidate of tocilizumab)CT-P47, containing the active ingredient tocilizumab, is a recombinant humanized monoclonal antibody that acts as an interleukin 6 (IL-6) receptor antagonist. Based on data from the global Phase III clinical trial designed to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of CT-P47 compared to reference tocilizumab, CT-P47 was filed for regulatory approval with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in January and February 2024, respectively. FORWARD-LOOKING STATEMENTCertain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion Inc./Celltrion USA that may constitute forward-looking statements, under pertinent securities laws.These statements may be identified by words such as "prepares", "hopes to", "upcoming", "plans to", "aims to", "to be launched", "is preparing, "once gained", "could", "with the aim of", "may", "once identified", "will", "working towards", "is due", "become available", "has potential to", the negative of these words or such other variations thereon or comparable terminology.In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion Inc./Celltrion USA's management, of which many are beyond its control.Forward-looking statements are provided to allow potential investors the opportunity to understand management's beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them.Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or result expressed or implied by such forward-looking statements.Such Risks and uncertainties may include, among other things, uncertainties regarding the launch timing and commercial success of Celltrion in the United States; the uncertainties inherent in supply chain, manufacturing, research and development, and the possibility of unfavorable new clinical data and further analyses of existing clinical data as it relates to Celltrion products; intellectual property and/or litigation/settlement implications; decisions by the FDA impacting labeling, manufacturing processes, safety, promotion, and/or other matters that could affect the availability or commercial potential of Celltrion products; and uncertainties regarding access challenges for our biosimilar products where our product may not receive appropriate formulary access or remains in a disadvantaged position relative to competitive products; and competitive developments. A further description of risks and uncertainties can be found in Celltrion's Annual Report.Although forward-looking statements are based upon what management of Celltrion Inc./Celltrion USA believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Celltrion Inc./Celltrion USA undertakes no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements. TrademarksPROLIA® and XGEVA® are registered trademarks of Amgen Inc.ACTEMRA® is a registered trademark of Chugai Seiyaku Kabushiki Kaisha Corp., a member of the Roche Group.References[1] Jean-Yves Reginster et al., Efficacy and Safety Results of CT-P41 (Proposed Denosumab Biosimilar) Compared to Reference Denosumab in Postmenopausal Women with Osteoporosis: 78-Week Results from Phase 3 Randomized Controlled Trial. Oral Presentation (abstract no. 2563). Presented at ACR 2024[2] Gerd Burmester et al., Similar Efficacy, PK, Safety, and Immunogenicity of Tocilizumab Biosimilar (CT-P47) and Reference Tocilizumab in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: Week 52 Results from the Phase III Single Transition Study. Poster Presentation (abstract no. 0502). Presented at ACR 2024.[3] Jean-Yves Reginster et al., Impact of Immunogenicity on Clinical Outcomes in Postmenopausal Women with Osteoporosis: Results from a Randomized Controlled Phase 3 Study to Compare CT-P41 (Proposed Denosumab Biosimilar) and Reference Denosumab. Poster Presentation (abstract no. 2144). Presented at ACR 2024.[4] Denosumab U.S. Prescribing Information (2024)

Celltrion announces acquisition of iQone Healthcare Switzerland, accelerating direct commercialization of its biosimilars in the European regionThe acquisition strengthens Celltrion’s presence in Europe, driving growth and expanding access to its innovative biosimilar treatments November 15, 2024 08:30 AM INCHEON, South Korea - Celltrion (KRX:068270), a global biopharmaceutical leader, announced its acquisition of iQone Healthcare Switzerland, a specialty pharmaceutical company focused on distribution, sales, and marketing in Switzerland. The acquisition, expected to close by Q4, 2024, represents a significant milestone in Celltrion’s European expansion strategy. Upon completion, iQone Healthcare Switzerland will become a wholly owned subsidiary of Celltrion Healthcare Hungary Kft. The deal will also provide Celltrion access to in-licensing opportunities, further strengthening its pipeline of innovative therapies. Taehun Ha, Head of Europe and Vice President of Celltrion, Inc., emphasized the acquisition’s importance, stating, “This move represents a strategic shift in our growth strategy. While we have successfully built direct sales networks, we are now leveraging acquisitions to accelerate our European expansion. With a distribution network spanning more than 20 regions, we are well-positioned to compete in the increasingly competitive biosimilar market.” He added, “As a fully integrated company, Celltrion manages every stage of the value chain—from R&D and manufacturing to sales, marketing and distribution. This integration enables us to continue and expand our stable and growing supply of high-quality biosimilars, including in Switzerland, where we aim to further solidify our market presence and portfolio. It also underscores our commitment to leadership through local operational excellence and continuous innovation.” Laurent Massuyeau, founder and Executive Chairman of iQone Healthcare Switzerland, expressed his optimism, stating, “Our successful decade-long partnership with Celltrion has laid very strong foundations for this integration. By combining Celltrion’s portfolio expertise with our established commercial operation, this acquisition will drive growth and enhance access to essential biosimilar and innovative medicines in Switzerland. True to our values and with the support of the program “iQone for You”, an outstanding set of services directed to healthcare professionals and specially crafted for the Swiss market, we will continue to serve our customers with agility and efficiency and bring new therapeutic opportunities quickly to Switzerland." About CelltrionCelltrion is a leading biopharmaceutical company based in Incheon, South Korea that specialises in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. The company’s solutions include world-class monoclonal antibody biosimilars such as Remsima®, Truxima® and Herzuma®, providing broader patient access globally. Celltrion has also received U.S. FDA and EC approval for Vegzelma® and Yuflyma®, FDA approval for Zymfentra®, and EC approval for Remsima® SC, Omlyclo®, SteQeyma®. To learn more, please visit www.celltrion.com/en-us. About iQone Healthcare SwitzerlandiQone Healthcare, a Swiss-based specialty pharmaceutical company, is dedicated to the commercialization of biosimilars and innovative treatments for rare diseases. Its mission is to ensure that therapeutic advancements are accessible to Swiss patients in a timely manner, providing the care they need when they need it. Through its long-standing collaborations with several global pharmaceutical developers and manufacturers, iQone Healthcare provides a continually expanding selection of leading biosimilars and innovative products to healthcare professionals and institutions in Switzerland.iQone Healthcare has maintained a decade-long partnership with Celltrion as exclusive distribution partner for Switzerland, successfully marketing Celltrion product range, including Remsima®, Veblocema®, Truxima®, Herzuma®, Vegzelma®, and Yuflyma®. For more information, visit www.iqone-healthcare.com FORWARD-LOOKING STATEMENTCertain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion Inc. and its subsidiaries that may constitute forward-looking statements, under pertinent securities laws.These statements may be identified by words such as “prepares”, “hopes to”, “upcoming”, ”plans to”, “aims to”, “to be launched”, “is preparing, “once gained”, “could”, “with the aim of”, “may”, “once identified”, “will”, “working towards”, “is due”, “become available”, “has potential to”, the negative of these words or such other variations thereon or comparable terminology.In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion Inc. and its subsidiaries' management, of which many are beyond its control.Forward-looking statements are provided to allow potential investors the opportunity to understand management’s beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them.Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or result expressed or implied by such forward-looking statements.Although forward-looking statements contained in this presentation are based upon what management of Celltrion Inc. and its subsidiaries believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Celltrion Inc. and its subsidiaries undertake no obligation to update forward-looking statements if circumstances or management’s estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements.

 Celltrion USA has expanded access to ZYMFENTRA® (infliximab-dyyb), the first and only FDA-approved subcutaneous (SC) infliximab, to a significant share of the U.S. market The availability of ZYMFENTRA will support greater patient access and choice while helping to drive greater affordability to patients and health care systems JERSEY CITY, N.J., Oct. 31, 2024 - Celltrion USA announced today that, through continued partnership with key PBMs and health plans, the company has expanded access to ZYMFENTRA® (infliximab-dyyb), the first and only U.S. Food and Drug Administration (FDA)-approved subcutaneous infliximab. With these partnerships Celltrion has now secured comprehensive access across the US health care system. ZYMFENTRA has attained access to a significant share of the U.S. market, providing an increase in availability to patients and prescribers. This achievement reflects unmet needs of patients, providers and payers, as well as Celltrion USA's ability to deliver on our strong heritage of supply, manufacturing and commitment to biologics. "Our extensive engagement with PBMs and health plans from the outset have led to the comprehensive expanded access for ZYMFENTRA in a short time frame," said Thomas Nusbickel, Celltrion USA Chief Commercial Officer (CCO). "This achievement underscores ZYMFENTRA's unique and innovative therapeutic advantages, and we look forward to expanding our outreach to deliver its treatment benefits to as many patients in the U.S. as possible." ZYMFENTRA was approved by the FDA in October 2023 through the Biologics License Application (BLA) under the 351 (a) pathway of the Public Health Service Act (a "stand-alone" BLA).  ZYMFENTRA is the first FDA-approved subcutaneous infliximab for the treatment of moderately to severely active ulcerative colitis and moderately to severely active Crohn's disease. About Celltrion USACelltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion currently has five biosimilars approved by the U.S. FDA: INFLECTRA® (infliximab-dyyb), TRUXIMA® (rituximab-abbs), HERZUMA® (trastuzumab-pkrb), VEGZELMA® (bevacizumab-adcd), and YUFLYMA®(adalimumab-aaty) as well as a novel biologic ZYMFENTRA®. Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence, and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. For more information, please visit: www.celltrionusa.com/. About ZYMFENTRA® (infliximab-dyyb)[1]ZYMFENTRA is a prescription medicine used as an injection under 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). ZYMFENTRA blocks the action of tumor necrosis factor-alpha (TNF-alpha), a protein that can be overproduced in response to certain diseases and cause the immune system to attack normal, healthy parts of the body.ZYMFENTRA® (infliximab-dyyb) was approved by the FDA through the Biologics License Application (BLA) under the 351 (a) pathway of the Public Health Service Act (a "stand-alone" BLA). ZYMFENTRA is considered a new biologic with a first-approved subcutaneous administration form and thus will be under patent protection for its dosage form by 2037 and for its route of administration by 2040. Indication and Important Safety InformationZYMFENTRA is a prescription medicine indicated in adults for maintenance treatment of:Moderately to severely active Crohn's disease following treatment with an infliximab product administered intravenously.Moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously. It is not known if ZYMFENTRA is safe and effective in children under 18 years of age. What is the most important information I should know about ZYMFENTRA? SERIOUS INFECTIONS Patients treated with ZYMFENTRA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis. Reported infections include:Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with ZYMFENTRA. Treatment for latent infection should be initiated prior to treatment with ZYMFENTRA.Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered 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. The risks and benefits of treatment with ZYMFENTRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with ZYMFENTRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.Risk of infection may be higher in patients greater than 65 years of age, patients with comorbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab included arthritis bacterial, pneumonia, and urinary tract infection. MALIGNANCIESMalignancies, some fatal, have been reported in children, adolescents, and young adults treated with TNF blockers, including infliximab products.Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants. Post-marketing cases of hepatosplenic T-cell lymphoma, 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. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis, and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with ZYMFENTRA, especially in these patient types. In clinical trials of all TNF blockers, more cases of malignancies were observed compared with controls and the expected rate in the general population. In clinical trials of some TNF blockers, including infliximab products, more cases of other malignancies were observed compared with controls. As the potential role of TNF blocker therapy in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy.Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. CONTRAINDICATIONSZYMFENTRA is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients of ZYMFENTRA or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness). HEPATITIS B VIRUS REACTIVATIONTNF blockers, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating ZYMFENTRA. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing ZYMFENTRA for patients identified as carriers of HBV, and monitor closely for active HBV infection during and following termination of therapy with ZYMFENTRA. Discontinue ZYMFENTRA in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of ZYMFENTRA, and monitor patients closely. HEPATOTOXICITYHepatobiliary disorders, including acute liver failure, jaundice abnormal hepatic function, hepatic steatosis, hepatitis, hepatotoxicity, hyperbilirubinemia, and non-alcoholic fatty liver, have been reported in patients receiving infliximab products post-marketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, ZYMFENTRA should be discontinued, and a thorough investigation of the abnormality should be undertaken. CONGESTIVE HEART FAILURECases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Some cases had a fatal outcome. In several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. ZYMFENTRA has not been studied in patients with a history of CHF and ZYMFENTRA should be used with caution in patients with CHF. HEMATOLOGIC REACTIONCases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to infliximab-product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of ZYMFENTRA in patients who develop significant hematologic abnormalities. HYPERSENSITIVITY AND OTHER ADMINISTRATION REACTIONSIn post-marketing experience, serious systemic hypersensitivity reactions (including anaphylaxis, hypotension, and serum sickness) have been reported following administration of infliximab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. INJECTION SITE REACTIONSIn clinical studies, localized injection-site reactions were reported following administration of ZYMFENTRA. If a clinically significant injection-site reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. NEUROLOGIC REACTIONSAgents that inhibit TNF have been associated with central nervous system (CNS) manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering ZYMFENTRA in patients with these disorders and consider discontinuation if these disorders develop. RISK OF INFECTION WITH CONCURRENT ADMINISTRATION OF OTHER BIOLOGICS PRODUCTSSerious infections and neutropenia have been reported with concurrent use of ZYMFENTRA with other immunosuppressive biological products. 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. RISK OF ADDITIVE IMMUNOSUPPRESSIVE EFFECTS FROM PRIOR BIOLOGICAL PRODUCTSConsider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA. AUTOIMMUNITYTreatment with TNF blockers may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue ZYMFENTRA treatment if symptoms of a lupus-like syndrome develop. VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTSPrior to initiating ZYMFENTRA, update vaccinations in accordance with current vaccination guidelines. Live vaccines or therapeutic infectious agents should not be given with ZYMFENTRA due to the possibility of clinical infections, including disseminated infections. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to ZYMFENTRA. ADVERSE REACTIONSIn clinical trials with ZYMFENTRA, the most common adverse reactions occurring in ≥3% of ZYMFENTRA -treated patients included site reactions, COVID-19, anemia, arthralgia, infection site reaction, increased alanine aminotransferase and abdominal pain for UC, and 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 for CD. Please click for Full U.S. Prescribing Information.Globally, prescribing information varies; refer to the individual country product label for complete information.[1] Zymfentra Prescribing Information