Celltrion USA is Committed to Delivering Advancements in IBD Treatments

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The health and economic burdens of inflammatory bowel disease (IBD) in the United States are on the rise. A recent study estimates 2.4 million Americans – or nearly 1 in 100 Americans – have Crohn’s disease or ulcerative colitis.¹ Not only do they suffer from IBD symptoms and flare-ups, but they also endure a higher number of hospitalizations, emergency room visits, and surgeries. In 2014, the economic impact of IBD in the U.S. was approximately $31.6 billion, which included direct healthcare costs and indirect costs related to absenteeism from work.²

With immunology as one of its key therapeutic areas, Celltrion USA is committed to meeting the need for affordable, accessible IBD treatment options. The company’s product portfolio includes the world's first biosimilar monoclonal antibody, which was developed by Celltrion and distributed by Pfizer in the U.S. market, to treat immune-mediated inflammatory diseases such as Crohn’s disease and ulcerative colitis. Since launching in the U.S. in 2016, the product has gained 31% market share, second only to the originator drug Remicade^®.

With the establishment of direct distribution and marketing in 2022, Celltrion USA has built a commercial infrastructure to strengthen its focus on immunology. As a leading global biopharmaceutical company, we are dedicated to developing biosimilars and next-generation biologics that improve health outcomes for patients suffering from IBD, while also serving as a reliable partner to ensure quality and access.

Unlocking the Potential of Biosimilars

Since the FDA approved the first monoclonal antibody biosimilar in 2015, a total of 43 biosimilars have been approved and made available to American patients.³ Remarkably, however, biosimilar market share in the United States is still low – particularly for immunology drugs, which were among the first biosimilars to be approved. That is now changing as the best-selling biopharmaceutical in the U.S., adalimumab (Humira®), faces biosimilar competition after a 20-year monopoly.

With the aim to offer providers and patients more treatment options through increased accessibility and affordability, Celltrion USA launched its TNF blocker biosimilar to treat autoimmune diseases in July 2023 following its FDA approval in May 2023. More than 80% of patients treated with Humira in the U.S. rely on a high-concentration and citrate-free formulation,⁴ and the availability of Celltrion’s biosimilar provided patients with one of the only biosimilars with a high-concentration, citrate-free formulation. Even more, Celltrion USA just announced in October 2023 that the FDA approved two doses of its adalimumab biosimilar, providing more dosing flexibility to meet the needs of patients and clinical practices.

Recently, Celltrion signed agreements with U.S. biotech company Rani Therapeutics to develop orally administered biosimilars. If approved, these drugs will use an oral delivery technology, known as the RaniPill^® capsule, intended to replace the subcutaneous or intravenous injections of the biologics with oral dosing. These treatments for inflammatory diseases, such as IBD, could offer patients an alternative method of drug administration, potentially providing more convenience in their disease management.

Celltrion has a robust pipeline and anticipates launching at least one biosimilar product every year, reaching a total of 18 products by 2030 in the U.S. market.

Expanding the Biologic Marketplace

As part of our commitment to address unmet patient needs, Celltrion has expanded beyond biosimilars with its first novel therapeutic to the U.S. market. Celltrion's subcutaneous formulation of infliximab, ZYMFENTRA^® (infliximab), received FDA approval in October 2023 as a new drug via the 351 (a) biologic license application (BLA) pathway. ZYMFENTRA* is approved for maintenance therapy in adults with moderately to severely active ulcerative colitis and Crohn’s disease following induction treatment with intravenous infliximab.⁵

This subcutaneous infliximab is a milestone therapeutic for the TNF inhibitor class, representing a key innovation after approximately 20 years of infliximab intravenous (IV) availability. With its approval, ZYMFENTRA is the first and only subcutaneous infliximab available in the U.S. and has the potential for improved clinical outcomes, delivering stable elevated serum infliximab levels above the target therapeutic concentration level. Additionally, ZYMFENTRA may provide more convenience and flexibility, as it can be self-administered at home rather than requiring patients to travel to a medical office to receive intravenous therapy.

Celltrion has prioritized developing biosimilar formulations and novel therapeutics that respond to market demands, such as the growing number of American patients in need of safe, effective, and economical IBD treatment options. In bringing our patient-centric approach and focus on immunology to the U.S. market, we are proud to support the IBD community through improved quality of care and cost-saving benefits to the U.S. health system.

References

1. Lewis, JD, Parlett LE, et. al. “Incidence, Prevalence and Racial and Ethnic Distribution of Inflammatory Bowel Disease in the United States.” Gastroenterology. July 2023.
2. Ananthakrishnan AN, Desai R, et. al. “Economic Burden of Fatigue in Inflammatory Bowel Disease.” Crohn’s & Colitis 360. April 2023; 5(3).
3. U.S. Food and Drug Administration. September 29, 2023.
4. Symphony Health, IQVIA
5. Zymfentra U.S. prescribing information (2023)

*ZYMFENTRA (infliximab-dyyb) U.S. Use and Important Safety Information

ZYMFENTRA is a prescription medicine indicated 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.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS INFECTIONS and MALIGNANCY

• Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens.
• Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis.
• Perform test for latent TB; if positive, start treatment for TB prior to starting ZYMFENTRA. Monitor all patients for active TB during treatment, even if initial latent TB test is negative.
• Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including infliximab.
• Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers including infliximab products. Almost all had received azathioprine or 6‑mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. The majority of cases were reported in patients with Crohn’s disease or ulcerative colitis, most of whom were adolescent or young adult males.

Contraindications:

• ZYMFENTRA is contraindicated in patients with a history of a severe hypersensitivity reaction to other infliximab products, any of its ingredients, or any murine proteins. Reactions have included anaphylaxis.

Warnings and Precautions

• Serious infections: Avoid in patients with active infection. If infection develops, conduct a prompt/complete diagnostic workup appropriate for immunocompromised patients and initiate antimicrobials. If systemic illness develops in patients who reside or travel to regions where mycoses are endemic, consider empiric antifungals.
• Malignancies: Malignancies, including lymphoma, were greater in TNF-blocker-treated patients. Consider the higher risk of hepatosplenic T-cell lymphoma (HSTCL) with combination therapy versus increased risk of immunogenicity and hypersensitivity reactions with monotherapy.
• Hepatitis B virus (HBV) reactivation: Test for HBV infection before starting treatment. Monitor HBV carriers during and several months after therapy for active HBV infection. If reactivation occurs, stop ZYMFENTRA and begin anti-viral therapy.
• Hepatotoxicity: Severe hepatic reactions, some fatal or necessitating liver transplantation have occurred in patients receiving infliximab products. Monitor hepatic enzymes and liver function tests every 3-4 months during treatment; investigate liver enzyme elevations and interrupt treatment if drug-induced liver injury is suspected. Instruct patients to seek immediate medical attention if symptoms develop.
• Congestive heart failure (CHF): New onset or worsening symptoms may occur. Avoid in patients with CHF. Monitor for new/worsening symptoms when administering ZYMFENTRA.
• Hematologic Reactions: Advise patients to seek immediate medical attention if signs and symptoms of cytopenia develop; consider stopping if significant hematologic abnormalities develop.
• Hypersensitivity and Other Administration Reactions: Serious hypersensitivity reactions, including anaphylaxis have occurred with intravenous formulations of infliximab; Discontinue ZYMFENTRA and start appropriate therapy.
• Neurologic Reactions: Exacerbation or new onset CNS demyelinating disorders may occur; consider discontinuation of ZYMFENTRA.
• Risk of infection with concurrent administration of other biological products: Concurrent use with other immunosuppressive biologics may increase risk of infection.
• Risk of additive immunosuppressive effects from prior biological products: Consider the half-life and mode of action of prior biologics.
• Autoimmunity: Formation of autoantibodies and development of lupus-like syndrome may occur; discontinue ZYMFENTRA if symptoms develop.
• Vaccinations and Use of Live Vaccines/Therapeutic Infectious Agents: Prior to initiating ZYMFENTRA bring patients up to date with vaccinations. Live vaccines or therapeutic infectious agents should not be given with ZYMFENTRA. A 6-month waiting period following birth is recommended before the administration of live vaccines to infants exposed in utero to infliximab.

Common Adverse Reactions (≥3%)

• Ulcerative Colitis: COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain.
• Crohn’s Disease: COVID-19, upper respiratory tract infection, headache, injection site reaction, diarrhea, increased alanine aminotransferase, and increased blood creatine phosphokinase, neutropenia, hypertension, urinary tract infection, dizziness, and leukopenia.

Drug Interactions

• Concurrent use with immunosuppressive biologics used to treat UC and CD is not recommended due to risk of infection.
• Formation of CYP450 enzymes may be suppressed by increased levels of cytokines during chronic inflammation. ZYMFENTRA could normalize the formation of CYP450 enzymes potentially resulting in decreased exposure of CYP450 substrates and requiring dose adjustments.

For more information about ZYMFENTRA, see full Prescribing Information including Boxed Warning.