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 infliximab
• The 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 /PRNewswire/ -- 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 Presentations

• Persistence, 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 USA

Celltrion 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 Information

ZYMFENTRA 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.

MALIGNANCIES
Malignancies, 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.

CONTRAINDICATIONS
ZYMFENTRA 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 REACTIVATION
TNF 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.

HEPATOTOXICITY
Hepatobiliary 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 FAILURE
Cases 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 REACTION
Cases 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 REACTIONS
In 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 REACTIONS
In 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 REACTIONS
Agents 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 PRODUCTS
Serious 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 PRODUCTS
Consider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA.

AUTOIMMUNITY
Treatment 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 AGENTS
Prior 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 REACTIONS
In 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 STATEMENT

Certain 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.

Contacts
Sarah Amundsen
[email protected]
+1 920-946-0918

SOURCE Celltrion USA