Celltrion USA signs agreement with Express Scripts for ZYMFENTRA™

JERSEY CITY, N.J., April 28, 2024 – Celltrion USA announced today that it has signed an agreement with Express Scripts, one of the nation’s leading pharmacy benefit managers (PBMs) negotiating on behalf of health plans covering more than 100 million people. The agreement, effective April 4, 2024 provides ZYMFENTRA Preferred Brand Access on the Express Scripts National Preferred Formulary serving 21.9 Million insured lives.  Express Scripts provides plan participants such as Health Plans of the PBM the ability to add ZYMFENTRA™ (infliximab-dyyb) to their formularies.

 

"This agreement opens up an important pathway for access to treatment for millions of patients with chronic diseases,” said Francine Galante, Vice President of Market Access at Celltrion USA. “We will continue to work with providers, patients and physicians to build upon our mission of developing transformational therapies that meet the needs of our patients living with chronic debilitating pain.”

 

Celltrion’s ZYMFENTRA, the first and only FDA-approved subcutaneous infliximab is now commercially available in the U.S. The company continues to engage with national and regional health plans, as well as Pharmacy Benefit Managers (PBMs) and Group Purchasing Organizations (GPOs), to communicate the value of its FDA-approved therapies including ZYMFENTRA for patients with autoimmune disease and to secure broad coverage.

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ZYMFENTRA™ (infliximab-dyyb) demonstrated long-term efficacy and safety profile of maintenance treatment through two years for adults with moderately to severely active Crohn's disease and ulcerative colitis

Findings from the extended LIBERTY studies and associated post-hoc analysis support the long-term efficacy and safety of ZYMFENTRA™, the first and only FDA-approved subcutaneous infliximab[1],[2]Data from a post-hoc analysis of the LIBERTY-CD study showed that, despite affecting drug levels, anti-drug antibodies (ADAs) status appeared to have no significant impact on W54 clinical outcomes or discontinuation rates [3] JERSEY CITY, N.J., May 21, 2024 - Celltrion USA announced today positive two-year results from the extended LIBERTY studies (LIBERTY-CD and LIBERTY-UC) for ZYMFENTRA™ (infliximab-dyyb) in adult patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) after induction with intravenous (IV) infliximab, further supporting the efficacy and safety seen in previous pivotal studies. The data was shared during 18 oral and poster presentations at the Digestive Disease Week® (DDW) 2024 Annual Meeting in Washington, D.C., from May 18 to 21.  The presentations included results of the two-year LIBERTY studies and a post-hoc analysis of the LIBERTY-CD study, which evaluated the impact of anti-drug antibodies (ADAs) on drug levels and efficacy in patients treated with ZYMFENTRA. "Establishing the long-term efficacy and safety profile of ZYMFENTRA is an important step as we work to bring relief and remission to the millions of people worldwide living with Crohn's disease and ulcerative colitis," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA. "These studies reaffirm efficacy and tolerance of ZYMFENTRA as maintenance therapy and underscore Celltrion USA's commitment to delivering different treatment options for patients in the gastroenterology space." Two-year extension phase of LIBERTY studiesThe extension phase of the LIBERTY studies (LIBERTY-CD and LIBERTY-UC) was carried out over a duration of 102 weeks (including 10 weeks of infliximab IV induction), expanding upon the initial LIBERTY trials. These two-year studies evaluated the long-term efficacy and safety of infliximab SC in patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC). In both LIBERTY-CD and UC studies, efficacy results, including but not limited to clinical remission, clinical response and corticosteroid-free remission, were generally well maintained at Week 102 compared to those of Week 54. Post-hoc analysis of LIBERTY-CD studyA post-hoc analysis evaluated the impact of ADAs on clinical outcomes in patients with CD who received infliximab SC maintenance treatment. The analysis comprised 231 patients (ADA-positive: n=150; ADA-negative: n=81) who received infliximab SC as maintenance treatment. Notably, there were no statistically significant differences in clinical outcomes at Week 54 between ADA-positive and ADA-negative patients. Although mean trough serum infliximab concentrations at Week 54 were notably lower in the ADA-positive group than in the ADA-negative group (11.7 vs. 19.3 μg/mL; p<0.00001), both groups exceeded the historical therapeutic target concentration of 5 μg/mL, with comparable discontinuation rates observed between the groups. "Results from the two-year extension phase LIBERTY studies, alongside post-hoc analysis, highlight important data supporting the efficacy and safety of ZYMFENTRA as a subcutaneous maintenance treatment option for people living with CD and UC," said Hetal Patel, Senior Director, Medical Affairs at Celltrion USA. "The post-hoc analysis reveals that ADAs showed no significant impact on clinical outcomes or discontinuation rates. These findings could be explained by the relatively high trough serum infliximab concentrations achieved by ADA-positive patients."[1],[2],[3] PEREM long term studyIn a large multi-center prospective cohort of inflammatory bowel diseases, the study assessed SC infliximab persistence, efficacy and tolerance after the switch from intravenous infliximab. The study enrolled 426 patients, with 72.4% diagnosed with Crohn's disease (CD). At baseline, 74% of participants were receiving the standard IV infliximab dose (5 mg/kg every 8 weeks), with 16% receiving combination therapy with an immunosuppressant. Drug persistence with SC infliximab was notably high at 95.3% among patients with complete data up to Week 48 (95% confidence interval: 93.2-97.5)[4]  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 new 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 Digestive Disease Week®Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 18-21, 2024. The meeting showcases more than 4,400 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org 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) and 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 a self-injected form of infliximab 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. Please click for Full U.S. Prescribing Information.Globally, prescribing information varies; refer to the individual country product label for complete information. References[1] Jean F. Colombel et al., Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn's disease: 2 years results of the LIBERTY-CD study. Poster (Su1762). Presented at DDW 2024.[2] Bruce E. Sands et al., Subcutaneous infliximab (CT-P13 SC) for ulcerative colitis: 2-year extension results of the LIBERTY-UC study. Poster (Su1779). Presented at DDW 2024.[3] Jean F. Colombel et al., Impact of immunogenicity on clinical outcomes in patients with Crohn's disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD study. Poster (Su1765). Presented at DDW 2024.[4] Nicolas Mathieu et al., Persistence, efficacy and tolerance of subcutaneous infliximab after switch from intravenous infliximab in IBD patients in remission: one-year results from a multicenter prospective cohort. Oral Presentation (1179). Presented at DDW 2024.

2024
05
21
Reality TV Star, Mollie Pearce, Backs Campaign to Tackle Inequalities in Condition That Impacts Millions of People Globally

Mollie Pearce, star of the UK reality TV show ‘The Traitors’ who was diagnosed with ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), at the age of 11, partners with Celltrion to launch a new campaign.World IBD Day 2024 sees Celltrion launch the second installation of the Where’s Crohn’s & Colitis (CC)? campaign, focused on global inequalities in access to IBD care and treatment.Mollie shares her experiences with UC to highlight the need for sustainable, equitable care that bridges the gap from diagnosis to treatment for all. INCHEON, South Korea – Celltrion partners with TV star Mollie Pearce to launch the second installation of the Where’s Crohn’s & Colitis (CC)? campaign for this year’s World IBD Day (19 May 2024). The campaign focuses on access to IBD care and treatment as the burden of the condition rises globally1. Widening inequalities and significant variations in access across the globe, and even within countries, is impacting people’s experience of IBD care and ultimately their outcomes2. Through raising awareness of the factors driving these inequalities and potential solutions, the campaign hopes to encourage improved access to a timely diagnosis, high quality care and innovative treatments. Innovations in treatments, including advances in treatment administration that enable people to access at-home injectable treatment (versus hospital-based treatment), allows people to have an improved quality of life whilst managing their condition3. The campaign encourages people to look beyond what they would usually see, to make the invisible condition, visible. In doing so, users are taken on a journey across borders to explore inequalities in IBD at a global scale and how these could be overcome. Reality TV star Mollie Pearce, a contestant on the popular UK show ‘The Traitors’, partners with Celltrion to launch the campaign. Mollie was diagnosed with UC when she was 11 years old and has openly shared her experiences living with the disease as an advocate for the IBD community, breaking down stigma and inspiring others to seek the care that works best for them. Mollie Pearce, media personality and finalist on ‘The Traitors’, commented: “Living with a condition such as UC comes with so many challenges - from sometimes not being able to leave the house to missing out on social occasions with friends. That’s why I’m so passionate about being an advocate for the IBD community and helping others to break down barriers and do the things they never thought were possible once they were diagnosed. “The Where’s CC? campaign is really close to my heart. I want to do all I can to ensure everyone is treated as an individual and gets the care they deserve.” Mr. Kevin Byoung Seo Choi, Executive VP and head of the marketing division at Celltrion, said: “It is simply unacceptable that there are so many barriers in accessing IBD care. From geographic disparities in access to infusion centers to health system limitations and education, there is an urgent need to tackle the root cause of inequalities globally so that all patients can access potentially life-changing therapies. “We are committed to tackling inequalities and ensuring a sustainable future for all IBD patients. The Where’s CC? campaign is our latest step in making this a reality through raising awareness and advocating for change.” The first instalment of the Where’s CC? campaign, launched for World IBD Day 2023, focused on age-related inequalities in IBD, and how the challenges that come with the condition can vary at different stages of life. Visit www.WhereIsCC.com to learn more about the Where’s CC? campaign and inequalities in access to care and treatment in IBD, and how these can be overcome to improve IBD outcomes for all. World IBD Day is an annual awareness campaign led by patient organisations representing over 50 countries on five continents and coordinated by the European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA)4. ABOUT INFLAMMATORY BOWEL DISEASE (IBD)IBD is an umbrella term used to describe conditions including Crohn’s disease and ulcerative colitis. Collectively, IBD impacts over 10 million people worldwide with incidence rates rapidly increasing across the world5. IBD is a long-term condition and there may be times when the symptoms are severe, known as a flare-up, and times when there are no or few symptoms, known as remission. Common symptoms of IBD include pain, cramping or swelling in the stomach, episodes of diarrhoea, weight loss and extreme tiredness6. IBD can appear for the first time at any age, however, diagnosis most commonly takes place between the ages of 10 and 405. Treatment for IBD can be transformative for patients’ lives, reducing the impact of the condition on their lives by minimising flare-ups and maintaining remission. In recent years, the increasing availability of new treatments has transformed IBD patient care. ABOUT ‘THE TRAITORS’‘The Traitors’ is a British reality TV series involving a group of players who are seemingly focused on a common goal – the ‘faithfuls’ must eliminate all the ‘traitors’ from the group. Mollie Pearce appeared in Series Two of the programme, making it to the final where she cast the deciding vote of the series. ABOUT CELLTRIONCelltrion is a leading biopharmaceutical company that specializes in research, development and manufacturing of innovative therapeutics that improve people's lives worldwide. The company’s portfolio of anti-TNF therapies spans a number of indications across distinct therapy areas: immunology, hemato-oncology and ophthalmology. We are dedicated to expanding patient access to life-changing biologic therapies while generating healthcare sustainability with meaningful cost savings for patients worldwide. 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/Celltrion Healthcare 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/Celltrion Healthcare'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. Although forward-looking statements contained in this presentation are based upon what management of Celltrion/Celltrion Healthcare 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/Celltrion Healthcare 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. References1 The Lancet Gastroenterology & Hepatology. Promoting equity in inflammatory bowel disease: a global approach to care. Available at: https://www.thelancet.com/journals/langas/article/PIIS2468-1253(23)00368-0/abstract#back-bib4 [Accessed: May 2024]2 Journal of Crohn’s and Colitis. P018 Inequalities in healthcare access, experience and outcomes in adults with Inflammatory Bowel Disease: A scoping review. Available at: https://academic.oup.com/ecco-jcc/article/18/Supplement_1/i269/7586146 [Accessed: May 2024]3 BMC Proceedings. Intravenous versus subcutaneous delivery of biotherapeutics in IBD: an expert’s and patient’s perspective. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654488/#:~:text=Benefits%20of%20the%20subcutaneous%20application%20of%20drugs%20include,are%20able%20to%20administer%20their%20treatments%20at%20home. [Accessed: May 2024]4 EFCCA. World IBD Day. Available at: https://worldibdday.org/ [Accessed: May 2024]5 EFCCA. What is IBD? Available at: https://efcca.org/content/what-ibd [Accessed: May 2024]6 NHS. Inflammatory bowel disease. Available at: https://www.nhs.uk/conditions/inflammatory-bowel-disease/ [Accessed: May 2024]

2024
05
19
Celltrion USA announces two-year data for ZYMFENTRA™(infliximab-dyyb) to be presented at Digestive Disease Week (DDW) 2024 Conference

Data presentations including the extended LIBERTY studies to highlight the long-term treatment goals of ZYMFENTRA™, the first and only FDA-approved subcutaneous infliximabThe data underscores Celltrion's commitment to improving patient outcomes and advancing scientific understanding in the field of IBD JERSEY CITY, N.J., May 17, 2024 - Celltrion USA today announced it will present the two-year results from the extended LIBERTY studies (LIBERTY-CD and LIBERTY-UC) in adult patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) receiving maintenance treatment after infliximab IV (intravenous) induction. The data will be shared during the Digestive Disease Week® (DDW) 2024 Annual Meeting in Washington, D.C., from May 18 to 21. "We are pleased to participate in this year's DDW and share our latest findings, including results from the two-year extension phase LIBERTY studies, alongside post-hoc analysis of the LIBERTY-CD study," said Nam Lee, Medical Director at Celltrion. "Following the U.S. launch of the first and only FDA-approved subcutaneous infliximab, ZYMFENTRA, we are thrilled to continue to share data showcasing our strong commitment to the IBD community." The clinical data from the extended LIBERTY studies and post-hoc analysis of the LIBERTY-CD study will be presented during 18 oral and poster presentations. The details of Celltrion USA's abstract presentations are as follows: Poster Presentations: Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn's disease: 2-year results of the LIBERTY-CD study (Poster #Su1762)Subcutaneous infliximab (CT-P13 SC) for ulcerative colitis: 2-year extension results of the LIBERTY-UC study (Poster #Su1779)Impact of immunogenicity on clinical outcomes in patients with Crohn's disease receiving maintenance treatment with subcutaneous infliximab: A post-hoc analysis of the LIBERTY-CD Study (Poster #Su1765)Impact of body mass index on clinical outcomes and drug levels in patients with Crohn's disease receiving maintenance treatment with subcutaneous infliximab: A post-hoc analysis of the LIBERTY-CD study (Poster #Su1755)Super-responders in patients with moderate-to-severe Crohn's disease treated with subcutaneous infliximab maintenance therapy: A post-hoc analysis of the LIBERTY-CD study (Poster #Su1767)Network meta-analysis to evaluate the comparative efficacy of advanced therapies as first line for maintenance treatment of adult patients with moderate-to-severe Crohn's disease (Poster #Mo1175)Effectiveness of switching from intravenous to subcutaneous infliximab in inflammatory bowel disease patients: A combined analysis of real-world evidence (Poster #Mo1854)Subcutaneous infliximab effectively manages clinical outcomes of inflammatory bowel disease independently of various confounding factors (Poster #Mo1869)Clinical efficacy and durability of subcutaneous infliximab in patients with inflammatory bowel disease after switching from intravenous infliximab (Poster #Mo1837)A prospective evaluation of clinical outcomes of subcutaneous infliximab following intravenous induction therapy in patients with Crohn's disease (Poster #Su1823)One-year clinical outcomes of switching to subcutaneous infliximab in patients with inflammatory bowel disease on maintenance of intravenous infliximab therapy with or without remission (Poster #Mo1826)Subcutaneous infliximab in Crohn's disease patients with immunogenic failure of intravenous infliximab (Poster #Mo1843)Intravenous to subcutaneous infliximab switch may reduce the risk of immunogenicity related treatment failure and can be used to facilitate immunomodulator withdrawal (Poster #Mo1856)Clinical efficacy and durability of subcutaneous infliximab in patients with moderate-to-severe inflammatory bowel disease (Poster #Mo1838)Rapid symptomatic improvement with subcutaneous infliximab induction treatment for patients with moderate to severe Crohn's disease (Poster #Sa1760)Pharmacokinetics of subcutaneous infliximab induction and maintenance in moderate-to-severely active Crohn's disease patients: weight matters (Poster #Su1811) Oral PresentationsPersistence, efficacy and tolerance of subcutaneous infliximab after switch from intravenous infliximab in IBD patients in remission: One-year results from a multi-center prospective cohort (Oral Presentation #1179)Effectiveness and safety of subcutaneous infliximab in perianal Crohn's disease: A multicentre cohort study (Oral Presentation #1176) 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 new 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 Digestive Disease Week ®Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 18-21, 2024. The meeting showcases more than 4,400 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org  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) and 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 a self-injected form of infliximab 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.Please click for Full U.S. Prescribing Information. Globally, prescribing information varies; refer to the individual country product label for complete information. 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 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 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.

2024
05
17
Celltrion USA's adalimumab-aaty biosimilar to HUMIRA® now available at low wholesale acquisition cost

Adalimumab-aaty will be priced at an 85% discount to HUMIRA® (adalimumab)Branded and unbranded versions of Celltrion USA's adalimumab biosimilar help provide more affordable options for patients JERSEY CITY, N.J., May 9, 2024 /PRNewswire/ -- Celltrion USA announced today that adalimumab-aaty, the company's high-concentration (100 mg/mL) and citrate-free formulation biosimilar to HUMIRA ® (adalimumab), is now available at a low wholesale acquisition cost (WAC). Adalimumab-aaty will be priced as WAC list price at an 85% discount to the current WAC list price of HUMIRA. Adalimumab-aaty is also available from Celltrion USA under the brand name YUFLYMA®, which launched in July 2023 and is available at a 5% discount to the current WAC list price of HUMIRA. Adalimumab-aaty is approved for the treatment of eight conditions, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa. "Access to medications in the U.S. has become increasingly complex, and there is so much value that biosimilars add with competition in the marketplace," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA. "The availability of branded and unbranded versions of adalimumab-aaty will improve the accessibility of adalimumab biosimilars in the U.S., providing economic benefits for patients and the overall healthcare system." Adalimumab-aaty is available as 40 mg/0.4mL, 80 mg/0.8mL and 20 mg/0.2mL. IMPORTANT SAFETY INFORMATION[1]This important safety information also applies to YUFLYMA® (adalimumab-aaty) SERIOUS INFECTIONSPatients treated with adalimumab-aaty are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.Discontinue adalimumab-aaty if a patient develops a serious infection or sepsis.Reported infections include:Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before adalimumab-aaty use and during therapy. Initiate treatment for latent TB prior to adalimumab-aaty 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 antifungal 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 adalimumab-aaty prior to initiating therapy in patients with chronic or recurrent infection.Monitor patients closely for the development of signs and symptoms of infection during and after treatment with adalimumab-aaty, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.Treatment with adalimumab-aaty should not be initiated in patients with an active infection, including localized infections.Patients over 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Discontinue adalimumab-aaty if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with adalimumab-aaty, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.Drug interactions with biologic products: In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of adalimumab-aaty with abatacept or anakinra is not recommended in patients with RA. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of adalimumab-aaty and other biologic products for the treatment of RA, PsA, AS, CD, UC, PS, and HS. Concomitant administration of adalimumab-aaty with other biologic DMARDs (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions. A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. MALIGNANCYLymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including adalimumab products. 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 adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority 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. It is uncertain whether the occurrence of HSTCL is related to the use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.Consider the risks and benefits of TNF blocker treatment including adalimumab-aaty prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC), or when considering continuing a TNF blocker in patients who develop a malignancy.In controlled portions of clinical trials of some adalimumab products, more cases of malignancies have been observed compared to control-treated adult patients.Non-melanoma skin cancer (NMSC) was reported during clinical trials for patients treated with adalimumab products. During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, PS and HS, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated patients and 0.2 (0.10, 0.59) per 100 patient-years among control-treated patients. Examine all patients, particularly those with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, for the presence of NMSC prior to and during treatment with adalimumab-aaty.In clinical trials of some adalimumab products, there was an approximately threefold higher rate of lymphoma than expected in the general U.S. population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to severalfold) than the general population for the development of lymphoma, even in the absence of TNF blockers.Postmarketing cases of acute and chronic leukemia were reported with the use of a TNF blocker in RA and other indications. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving adalimumab were lymphomas; other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. HYPERSENSITIVITYAnaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of adalimumab-aaty and institute appropriate therapy. HEPATITIS B VIRUS REACTIVATIONUse of TNF blockers, including adalimumab-aaty, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal.Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy.Exercise caution in prescribing TNF blockers for patients identified as carriers of HBV and closely monitor such patients for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy.In patients who develop HBV reactivation, stop adalimumab-aaty and initiate effective antiviral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of adalimumab-aaty therapy in this situation and monitor patients closely. NEUROLOGIC REACTIONSUse of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome.Exercise caution in considering the use of adalimumab-aaty in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of adalimumab-aaty should be considered if any of these disorders develop.There is a known association between intermediate uveitis and central demyelinating disorders. HEMATOLOGIC REACTIONSRare reports of pancytopenia including aplastic anemia have been reported with TNF blocking agents.Adverse reactions of the hematologic system, including medically significant cytopenia, have been infrequently reported with adalimumab products.Consider discontinuation of adalimumab-aaty therapy in patients with confirmed significant hematologic abnormalities. HEART FAILURECases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab products.Exercise caution when using adalimumab-aaty in patients who have heart failure and monitor them carefully. AUTOIMMUNITYTreatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab-aaty, discontinue treatment. IMMUNIZATIONSPatients on adalimumab-aaty may receive concurrent vaccinations, except for live vaccines.It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating adalimumab-aaty therapy.No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab products.The safety of administering live or live-attenuated vaccines in infants exposed to adalimumab in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. ADVERSE REACTIONSThe most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. INDICATIONSAdalimumab-aaty is a tumor necrosis factor (TNF) blocker indicated for:Rheumatoid Arthritis (RA): reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RAJuvenile Idiopathic Arthritis (JIA): reducing signs and symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and olderPsoriatic Arthritis (PsA): reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active PsAAnkylosing Spondylitis (AS): reducing signs and symptoms in adult patients with active ASCrohn's Disease (CD): treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and olderUlcerative Colitis (UC): treatment of moderately to severely active ulcerative colitis in adultsLimitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockersPlaque Psoriasis (Ps): treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriateHidradenitis Suppurativa (HS): treatment of adult patients with moderate to severe hidradenitis suppurativa Please see full Prescribing Information including Boxed Warning for adalimumab-aaty  About adalimumab-aaty[1]Adalimumab-aaty is an unbranded version of YUFLYMA® (CT-P17, biosimilar adalimumab).   YUFLYMA is a recombinant fully human anti–tumour necrosis factor α (anti-TNFα) monoclonal antibody. YUFLYMA is FDA-approved for the treatment of patients with rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis and Hidradenitis Suppurativa. Following the launch of 40mg/0.4mL in July 2023 and 80mg/0.8mL in December 2023, additional dosage form of 20mg/0.2mL was launched in the U.S. in March 2024. 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 new 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/ 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 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 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. TrademarksHUMIRA® is a registered trademark of AbbVie Biotechnology Ltd.YUFLYMA® is a registered trademark of Celltrion, Inc., used under license. References[1] Adalimumab-aaty U.S. prescribing information US-YUF-24-00007 04/24

2024
05
10
Celltrion USA signs agreement with Express Scripts for its therapy for autoimmune diseases including the first FDA-approved subcutaneous infliximab ZYMFENTRA™

JERSEY CITY, N.J., April 28, 2024 /PRNewswire/ -- Celltrion USA announced today that it has signed an agreement with Express Scripts, one of the nation's leading pharmacy benefit managers (PBMs) negotiating on behalf of health plans covering more than 100 million people. The agreement, effective April 4, 2024 provides ZYMFENTRA Preferred Brand Access on the Express Scripts National Preferred Formulary serving 21.9 Million insured lives. Express Scripts provides plan participants such as Health Plans of the PBM the ability to add ZYMFENTRA™ (infliximab-dyyb) to their formularies. "This agreement opens up an important pathway for access to treatment for millions of patients with chronic diseases," said Francine Galante, Vice President of Market Access at Celltrion USA. "We will continue to work with providers, patients and physicians to build upon our mission of developing transformational therapies that meet the needs of our patients living with chronic debilitating pain." Celltrion's ZYMFENTRA, the first and only FDA-approved subcutaneous infliximab is now commercially available in the U.S. The company continues to engage with national and regional health plans, as well as Pharmacy Benefit Managers (PBMs) and Group Purchasing Organizations (GPOs), to communicate the value of its FDA-approved therapies including ZYMFENTRA for patients with autoimmune disease and to secure broad coverage. 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 new 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. [1] Zymfentra Prescribing Information

2024
04
29
Latest Developments Regarding the Agreement with PBMs for Yuflyma

Celltrion is pleased to announce the successful closure of a deal with one of the top three leading pharmacy benefit managers(PBMs) in the US for the formulary inclusion of Yuflyma, following our recent successful listing agreement for Zymfentra.  Celltrion wishes to share this news preliminarily via our website and will provide further details following our discussions with the PBM.  Celltrion has recently announced the successful closure of the deal with one of the top three PBMs in the US for the formulary inclusion of Zymfentra. Concurrently, we have finalized a listing contract for our adalimumab biosimilar Yuflyma ('Humira' as the reference product) with the same PBM. We appreciate your understanding that, at this stage, we are unable to disclose the name of the PBM.  This listing of Yuflyma marks our second contract signed with the top three PBMs, following the previous listing in OptumRx’s formulary last year. Yuflyma is estimated to have attained coverage for approximately 50% of the US insurance market (measured by the number of lives covered) solely through these two PBMs. Celltrion views the significance of this agreement from three primary perspectives.   First and foremost, it is noteworthy that Celltrion has successfully executed its pivotal strategy of 'double pricing' for the sales of Yuflyma in the US market. Celltrion places profitability as the foremost consideration in negotiations with PBMs in the overly crowded US adalimumab market. Under last year’s agreement with Optum, Celltrion provided high-WAC (Wholesale Acquisition Cost) products to the public insurance market, where the rebate proportion is lower compared to the commercial insurance market. Conversely, as evidenced in the current agreement, we have provided low-WAC products to the commercial insurance market, where the rebate proportion is relatively higher. Through this strategic approach, we have established a pricing structure aimed at optimizing profitability across the varied dynamics of the US market.This contract reflects Celltrion’s strategic move in anticipation of the Inflation Reduction Act (IRA) implications starting in 2025. The IRA mandates insurance companies to cover 60% of excess costs for medications exceeding $2,000 in annual out-of-pocket prescription costs, heralding a shift towards favoring products characterized by both low rebates and low-WAC. In a proactive move to better navigate the forthcoming regulatory landscape, Celltrion strategically secured a competitive edge by including low-WAC and low-rebate products in industry-leading PBMs' formularies. The advantage of a low WAC extends beyond reduced out-of-pocket costs for patients—it also facilitates more favorable rebate negotiations with insurers, thereby strengthening Celltrion's profitability. Another significant aspect of this PBM contract is its facilitation of a strategic bundling of Zymfentra and Yuflyma for U.S. IBD specialists. The inclusion of Yuflyma in commercial plans expands options with an equally safe and effective biosimilar to Humira, complemented by Zymfentra, which presents an innovative approach for IBD treatment as the world's first and only subcutaneous infliximab. The anticipated rollout of the Stelara biosimilar, CT-P43, is expected to further solidify Celltrion's position in the IBD treatment landscape, driving prescription growth across its portfolios through enhanced market preference and cross-selling synergies. Furthermore, this agreement lays a robust groundwork for Celltrion to broaden the target market for Yuflyma into rheumatoid arthritis (RA), another significant indication of adalimumab, starting in the year’s second half. This enabled Yuflyma to target the entire Humira’s US market, valued at $18.62 billion (approximately KRW 24.2 trillion, as of 2022).  Celltrion remains dedicated to expediting contracts with the remaining major PBM and extending its efforts to medium and small-sized PBMs. By the year's first half, the company is determined to implement all necessary measures to gear itself for a quantum jump this year in the world's largest pharmaceutical market. Under the leadership of Chairman Jungjin Seo, the Celltrion team is fully engaged in ongoing sales endeavors across the U.S. to ensure that not only the company’s flagship product, Zymfentra, but also Yuflyma, Vegzelma, and its entire product portfolio achieve notable sales success.  Celltrion remains committed to maintaining timely communication channels with its shareholders. 

2024
04
11
Response to Inquiries Regarding the Inclusion of Zymfentra in PBM Formularies

Celltrion has received numerous inquiries from shareholders and analysts about the inclusion of Zymfentra, the world’s first and only subcutaneous infliximab, in Pharmacy Benefit Manager(PBM) formularies since its launch. We understand the significance of this request and are pleased to announce through our website that we have successfully closed a deal with one of the top three PBMs in the US, resulting in Zymfentra’s inclusion in their formulary. We will provide further details once our discussions with the PBM are concluded. As outlined during our recent Annual General Meeting, Celltrion has been actively engaging with various PBMs for the formulary inclusion of Zymfentra upon its launch in the US market. We are thrilled to report the successful closure of a significant deal with one of the three major PBMs, which collectively dominate a substantial portion of the insurance market in the US. This milestone is particularly noteworthy, given the achievement within just half a month since the product's launch. While we are excited to share the details of this agreement with you, we must adhere to contractual obligations, preventing us from disclosing the name of the PBM at this time. With this latest agreement and additional contracts signed with multiple mid-sized PBMs, Zymfentra has captured approximately 40% of the private health insurance market, measured by the number of lives covered.  Notably, in certain Western US regions, Zymfentra has already been swiftly listed in the formulary of an insurer affiliated with the PBM, facilitating ongoing prescriptions. In tandem with this achievement, Celltrion is actively implementing patient support programs to drive faster uptake of Zymfentra. For PBMs nearing the finalization of formulary listing agreements, Celltrion initiated the “Start Program” to offer temporary access for patients at no cost until payer coverage is established. Patients have started enrolling in this program with numerous inquiries about eligibility. Celltrion is also facilitating co-pay support for eligible patients, further expanding patient access to Zymfentra. These patient-centric initiatives are anticipated to fuel preferences for Zymfentra, thereby stimulating sales growth. Chairman JungJin Seo, alongside the dedicated Celltrion USA team, has played a pivotal role in securing this landmark deal. Chairman Seo will continue actively engaging in the US market, fostering relationships with key stakeholders, including local medical professionals. Building upon this success, Celltrion is committed to expediting agreements with the remaining two major PBMs and small-to-mid-sized PBMs. Our focus extends beyond the closure of PBM contracts; we are steadfast in our commitment to translate this accomplishment into tangible revenue. Celltrion remains dedicated to driving the success of Zymfentra while ensuring timely communication with our valued shareholders.  We extend our sincere gratitude for your unwavering support and confidence in Celltrion. 

2024
04
08
Notice to shareholders regarding: The conclusion of the financial regulator’s audit inspection and the Securities & Futures Commission’s review

■ During the last 47 months, since Apr 2018, we have sincerely participated in the audit conducted by the financial authorities on its financial statements for 12 fiscal years. We have faithfully explained our position on the issues raised during this audit. As the decisions announced by Securities & Futures Commission (SFC) on Mar 11, 2022, officially mark the finalization of this audit, we believe that these decisions eliminate a significant portion of the uncertainty about Celltrion that has existed in the financial market for a long time. These decisions also clear up some of the misunderstandings caused by the differences in opinion between the financial authorities and Celltrion. ■ It is unfortunate that SFC has found some of our accounting practices in violation of the accounting standards. While we believe that these findings were caused by the different views on how the unique nature of biopharmaceuticals and the relevant international rules are incorporated into our accounting exercises, we respectfully accept SFC’s decisions. ■ The accounting practices that were viewed as violations of the accounting standards occurred in the past, hence having a limited impact on our current financial statements. ■ With the audit inspection finally resolved, we and the affiliates of Celltrion Group will remain committed to our key business to meet the market and shareholder expectations.

2022
03
11
Celltrion’s Statement on the development of a therapeutic antibody treatment to combat COVID-19

■ Celltrion Group was among the first that have embarked on the development of a therapeutic antibody treatment and a diagnostic kit on the onset of the global spread of the novel coronavirus, in a bid to contribute to stopping what would escalate into the coronavirus pandemic. ■ As Celltrion Group Chairman Seo Jung-jin has said earlier, the development of these solutions is driven by our commitment to placing the public interest before our own. Simply put, we are acting on our responsibility as a faithful member of the global pharmaceutical community as we willingly step forward  to help address the global coronavirus pandemic. ■ Our researchers are working round the clock to contribute to the world’s common battle to defeat the COVID-19 pandemic. We ensure that any significant progress is promptly, and transparently, shared with the world, because we would like to give the people a sense of hope that we are moving towards an end of these difficult times.  ■ We advise our investors to understand that our efforts to develop a coronavirus treatment and a  diagnostic kit are not commercially motivated, and their investment decisions should be made based on our business records and the underlying value of our product portfolio.  ■ Leading the global antibody biosimilar market, we have been growing continuously on the back of our robust fundamentals. With the successful development and global launches of monoclonal antibody biopharmaceuticals such as Remsima, Truxima, Herzuma, and Remsima SC, Celltrion is becoming a global pharmaceutical corporation representing South Korea.  ■ We ask for your continued interest in our vision for future growth as we continue to build upon our own technological capabilities and R&D know-how.

2020
04
13