Celltrion

• YUFLYMA^® (adalimumab-aaty), a high-concentration (100 mg/mL) and citrate-free formulation of HUMIRA^® (adalimumab) biosimilar, is now available in 80 mg 

  dose 

• Celltrion USA plans to launch a 20 mg dose option in late Q1 2024

January 17, 2024, JERSEY CITY, NJ – Celltrion USA announced today the launch of an 80mg dose of YUFLYMA^® (adalimumab-aaty), a high-concentration (100mg/mL) and citrate-free formulation of HUMIRA^® (adalimumab) biosimilar, in the United States. 

YUFLYMA is currently available in a single 40 mg dose in both a prefilled syringe with safety guard and autoinjector. The addition of an 80 mg dose will offer more choice and dosage flexibility for patients and clinical practices. YUFLYMA 80 mg is offered at the same price as YUFLYMA 40 mg to meet the needs of patients, prescribers, and payers. In addition, a 20 mg dose of YUFLYMA is expected to be available in pharmacies in late Q1 2024.

More than 80% of patients treated with HUMIRA in the U.S. rely on a high-concentration and citrate-free formulation.[1] YUFLYMA is a citrate-free formulation that is highly concentrated at 100mg/mL. It also maintains stability at 25℃ (77°F) for 31 days, with protection from light, and is a latex-free device.[2]

“YUFLYMA demonstrated a comparable efficacy, safety, pharmacokinetics, and immunogenicity profile as the reference product,” said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA.  “These new dose amounts and the auto-injector option provide flexible regimens. These new dose amount and the 2 step auto-injector option provide flexibility and convenient self-administration.”

To enhance patients’ and healthcare providers’ experience using YUFLYMA, Celltrion USA offers the Celltrion CONNECT^® Patient Support Program along with the Celltrion CARES™ Co-pay Assistance Program. The Patient Support Program for YUFLYMA will provide benefits verification, prior authorization assistance, and co-pay assistance. Eligible patients with private/commercial insurance may receive YUFLYMA for as little as $0 out of pocket per month. Patients who are uninsured or underinsured may be eligible to receive YUFLYMA through the Celltrion CONNECT^® Patient Assistance Program (PAP). Through these support programs, nurses are available to answer patients’ questions and provide training. Visit www.CelltrionConnect.com to learn more.

Notes to Editors:

About YUFLYMA^® (CT-P17, biosimilar adalimumab-aaty)²
YUFLYMA is the world’s first proposed high-concentration, low-volume and citrate-free adalimumab biosimilar to receive European Commission approval in Europe. 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. YUFLYMA is a recombinant fully human anti–tumour necrosis factor α (anti-TNFα) monoclonal antibody. Following the launch of 40mg/0.4mL in July 2023 and 80mg/0.8mL in December 2023, Celltrion additionally plans to launch additional dosage form of 20mg/0.2mL in the U.S. in late 1Q 2024.

YUFLYMA^® IMPORTANT SAFETY INFORMATION²

SERIOUS INFECTIONS

Patients treated with YUFLYMA 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 YUFLYMA 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 YUFLYMA use and during therapy. Initiate treatment for latent TB prior to YUFLYMA 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 YUFLYMA 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 YUFLYMA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

• Treatment with YUFLYMA 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 methotr

  exate), may be at greater risk of infection. Discontinue YUFLYMA if a patient develops a serious infection or sepsis. For a patient who develops a new infection 

• during treatment with YUFLYMA, 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 o

  f TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of YUFLYMA 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 block

  er. There is insufficient information regarding the concomitant use of YUFLYMA and other biologic products for the treatment of RA, PsA, AS, CD, UC, PS, and 

  HS. Concomitant administration of YUFLYMA with other biologic DMARDs (e.g., anakinra and abatacept) or other TNF blockers is not recommended based up

  on the possible increased risk for infections and other potential pharmacological interactions. A higher rate of serious infections has been observed in RA patie

  nts treated with rituximab who received subsequent treatment with a TNF blocker.

MALIGNANCY

Lymphoma 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 YUFLYMA prior to initiating therapy in patients with a known malignancy other than a succe

  ssfully 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 patien

  ts.

• Non-melanoma skin cancer (NMSC) was reported during clinical trials for patients treated with adalimumab products. During the controlled portions of 39 glob

  al 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 pati

  ent-years among adalimumab-treated patients and 0.2 (0.10, 0.59) per 100 patient-years among control-treated patients. Examine all patients, particularly thos

  e 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 YUFLYMA.

• In clinical trials of some adalimumab products, there was an approximately threefold higher rate of lymphoma than expected in the general U.S. population. Pati

  ents 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 postmar

  keting 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 adols

  scents.

HYPERSENSITIVITY

• Anaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If an anaphylactic or other serious allergic reactio

  n occurs, immediately discontinue administration of YUFLYMA and institute appropriate therapy.

HEPATITIS B VIRUS REACTIVATION

• Use of TNF blockers, including YUFLYMA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. In some instance

  s, 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 activ

  e HBV infection throughout therapy and for several months following termination of therapy.

• In patients who develop HBV reactivation, stop YUFLYMA 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 YUFLYMA therapy in this sit

  uation and monitor patients closely.

NEUROLOGIC REACTIONS

• Use of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or ra.

  diographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating diseas

  e, including Guillain-Barré syndrome. 

• Exercise caution in considering the use of YUFLYMA in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; 

  discontinuation of YUFLYMA should be considered if any of these disorders develop. 

• There is a known association between intermediate uveitis and central demyelinating disorders.

HEMATOLOGIC REACTIONS

• Rare 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 YUFLYMA therapy in patients with confirmed significant hematologic abnormalities.

HEART FAILURE

• Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been obser

  ved with adalimumab products.

• Exercise caution when using YUFLYMA in patients who have heart failure and monitor them carefully.

AUTOIMMUNITY

• Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develo

  ps symptoms suggestive of a lupus-like syndrome following treatment with YUFLYMA, discontinue treatment.

IMMUNIZATIONS

• Patients on YUFLYMA 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 in

  itiating YUFLYMA 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 REACTIONS

• The most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, a

  nd rash.

INDICATIONS

YUFLYMA 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 physi

  cal function in adult patients with moderately to severely active RA

• Juvenile Idiopathic Arthritis (JIA): reducing signs and symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and older

• Psoriatic Arthritis (PsA): reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with a

  ctive PsA

• Ankylosing Spondylitis (AS): reducing signs and symptoms in adult patients with active AS
• Crohn’s Disease (CD): treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older
• Ulcerative Colitis (UC): treatment of moderately to severely active ulcerative colitis in adults

Limitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers

• Plaque Psoriasis (Ps): treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, a

  nd when other systemic therapies are medically less appropriate

• Hidradenitis Suppurativa (HS): treatment of adult patients with moderate to severe hidradenitis suppurativa

Please see full Prescribing Information for YUFLYMA^® (adalimumab-aaty) 

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/

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.

Trademarks

HUMIRA is a registered trademark of AbbVie.

YUFLYMA^® is a registered trademark of Celltrion, Inc., used under license.

References 

[1] Symphony Health, IQVIA

[2] YUFLYMA U.S. prescribing information