Abatacept

YUFLYMA ® (adalimumab-aaty) is a high-concentration (100mg/mL) and citrate-free formulation of Humira ® (adalimumab) biosimilar, that is now interchangeable [1] Interchangeable designation of YUFLYMA ® is supported by positive data from the Phase III interchangeability study in patients with moderate-to-severe plaque psoriasis INCHEON, South Korea, April 14, 2025 /PRNewswire/ -- Celltrion, Inc. today announced that the U.S. Food and Drug Administration (FDA) has designated YUFLYMA ® (adalimumab-aaty), as an interchangeable biosimilar to Humira ® (adalimumab). YUFLYMA is an FDA-approved, high-concentration (100mg/mL) and citrate-free formulation of Humira® biosimilar, approved for multiple inflammatory indications.[1] "With this new designation, YUFLYMA is further positioned to help more patients gain access to and afford the therapy they need," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA. "YUFLYMA has the same dosage form, route of administration, and dosing regimen as the reference product. The pharmacist's ability to substitute the biosimilar directly at the pharmacy without the hassle of a new prescription and without the patient having to learn a new method of administration can be a game changer in increasing patient access to adalimumab." The interchangeable designation was supported by data from the Phase III interchangeability study, which demonstrated similar outcomes in terms of pharmacokinetics, efficacy, safety and immunogenicity in patients with moderately to severely active plaque psoriasis who received reference adalimumab (ADA) continuously and those who alternated between reference ADA and YUFLYMA during the dosing interval of Week 25-27. The result of the interchangeability study was presented at the European Academy of Dermatology & Venereology (EADV) 2024.[2] FDA-approved interchangeable biosimilars may be substituted for the reference product at the pharmacy without the intervention of the prescribing health care provider, subject to state laws.[3] The high-concentration form of YUFLYMA was FDA-approved in May 2023 and is currently available as 20mg, 40 mg and 80mg solution for injection in a prefilled syringe and in an autoinjector pen. YUFLYMA was introduced into the US commercial market on July 2, 2023. YUFLYMA is available in two pricing options to help provide more affordable options for patients. Adalimumab-aaty, the unbranded version, is priced at an 85% discount to the current wholesale acquisition cost (WAC) list price of Humira (adalimumab), providing economic benefits for patients and overall healthcare system. The branded version is priced at a 5% discount to the current WAC of Humira (adalimumab). Notes to Editors: About YUFLYMA® (CT-P17, biosimilar adalimumab-aaty)[1] YUFLYMA is the world's first proposed high-concentration, low-volume and citrate-free adalimumab biosimilar to receive European Commission approval. 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, hidradenitis suppurativa and uveitis. YUFLYMA has been designated by the FDA as an interchangeable biosimilar in a prefilled syringe. YUFLYMA is a recombinant fully human anti–tumor necrosis factor α (anti-TNFα) monoclonal antibody. YUFLYMA is available in 20mg/0.2mL, 40mg/0.4mL and 80mg/0.8mL. IMPORTANT SAFETY INFORMATION[1] This important safety information also applies to YUFLYMA® (adalimumab-aaty) SERIOUS INFECTIONS Patients 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. 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 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, HS and UV, 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. HYPERSENSITIVITY Anaphylaxis 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 REACTIVATION Use 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 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 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 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 adalimumab-aaty 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 observed with adalimumab products. Exercise caution when using adalimumab-aaty 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 develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab-aaty, discontinue treatment. IMMUNIZATIONS Patients 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 REACTIONS The most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. INDICATIONS Adalimumab-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 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 active 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, and when other systemic therapies are medically less appropriate Hidradenitis Suppurativa (HS): treatment of adult patients with moderate to severe hidradenitis suppurativa Uveitis (UV): treatment of non-infectious intermediate, posterior, and panuveitis in adult patients For Yuflyma (adalimumab-aaty): Please click for Full U.S. Prescribing Information. For adalimumab-aaty: Please see Full U.S. Prescribing Information. Globally, prescribing information varies; refer to the individual country product label for complete information. About Celltrion , Inc. Celltrion is a leading biopharmaceutical company that specializes in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. Celltrion is a pioneer in the biosimilar space, having launched the world's first monoclonal antibody biosimilar. Our global pharmaceutical portfolio addresses a range of therapeutic areas including immunology, oncology, hematology, ophthalmology and endocrinology. Beyond biosimilar products, we are committed to advancing our pipeline with novel drugs to push the boundaries of scientific innovation and deliver quality medicines. For more information, please visit our website and stay updated with our latest news and events on our social media: LinkedIn, Instagram, X, and Facebook. 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's FDA-approved biosimilar products in immunology, oncology, hematology, and endocrinology include: INFLECTRA® (infliximab-dyyb), TRUXIMA® (rituximab-abbs), HERZUMA® (trastuzumab-pkrb), VEGZELMA® (bevacizumab-adcd), YUFLYMA®(adalimumab-aaty), AVTOZMA® (tocilizumab-anho), STEQEYMA® (ustekinumab-stba), STOBOCLO® (denosumab-bmwo), OSENVELT® (denosumab-bmwo) and OMLYCLO® (omalizumab-igec), as well as the novel biologic ZYMFENTRA® (infliximab-dyyb). 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 and stay updated with our latest news and events on our social media: LinkedIn. 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, Inc. and its subsidiaries that may constitute forward-looking statements under pertinent securities laws. This press release contains forward looking statements. These statements may be also 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", "anticipate" the negative of these words or such other variations thereon or comparable terminology. In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion, Inc. and its subsidiaries' management, of which many are beyond its control. Forward-looking statements are provided to allow potential investors the opportunity to understand management's beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them. Such forward-looking statements necessarily involve known and unknown risks and uncertainties associated with the company's business, including the risk factors disclosed in its Annual Report and/or Quarterly Reports, 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 statements. Celltrion, Inc. and its subsidiaries undertake no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws. Trademarks Humira is a registered trademark of AbbVie. YUFLYMA® is a registered trademark of Celltrion, Inc., used under license. References [1] YUFLYMA US prescribing information (2023) [2] Lebwohl M et al., Pharmacokinetics, Efficacy and Safety after Multiple Switches from Reference Adalimumab to Adalimumab Biosimilar (CT-P17) in comparison with the Maintenance Group (Reference Adalimumab) in Patients with Moderate-toSevere Plaque Psoriasis: Week 27 Results from the Phase III Interchangeability Study. [EADV 2024, Poster number P0931]. Available at: [3] 9 Things to Know About Biosimilars and Interchangeable Biosimilars. Available at : For further information please contact:  Andria Arena [email protected] +1 516-578-0057 SOURCE Celltrion WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

PREFACE 前言 PD-(L)1抑制剂改变了肿瘤治疗格局，既是第一代肿瘤免疫的基石，也是目前双/多抗、联合疗法，以及ADC开发的重点方向。 另一边，免疫检查点的“一体两面”，也使得PD-1激动剂有望剑指自免大蓝海。 近期，PD-L1 ADC和PD-1激动剂两条尚未陷入“内卷”赛道纷纷迎来了关键进展，国内药企的前瞻布局，也有了新的故事可以讲述。 01 PD-1激动剂， AnaptysBio突破，国内金赛领先 PD-1和CTLA-4是两个经典的免疫检查点。在CTLA-4的研究上，BMS研发出了Abatacept和Lpilimumab两款经典药物，分别用于治疗自身免疫性疾病和肿瘤。 而PD-1在自免领域的探索，不如CLTA-4“顺利”。2023年5月，礼来宣布其PD-1激动剂Peresolimab治疗类风湿关节炎（RA）临床2a期试验达到了主要终点和部分次要终点，成为了PD-1激动剂能够有效治疗自免疾病的首个临床证据。 但其他次要终点，ACR50和ACR70响应方面并无显著优势，安全性方面也没有明显的优势，副作用发生率与安慰剂组相当，这也为礼来日后的决策埋下了“伏笔”。 最终礼来在2024年Q3的财报中删除了Peresolimab，这也导致另一家开发PD-1激动剂的Anaptysbio股价大跌28%。 礼来的“退出”，并不是PD-1激动剂赛道的“终点”。3个月后，AnaptysBio宣布PD-1激动剂Rosnilimab治疗类风湿关节炎（RA）的2b期临床取得成功，股价大涨30%。 从机制上来看，Rosnilimab实现突破的关键在于针对膜近端表位，与Peresolimab不同。 2023年1月，Suzuki和Tajima等科学家在Science Immunology上发表的论文（DOI: 10.1126/sciimmunol.add4947）表明，PD-1阻断抗体会结合膜远端区域（membrane-distal region），而PD-1激动性抗体则结合到膜近端细胞外区域(membrane-proximal extracellular region），表明结合膜近端表位或许是PD-1激动剂开发的关键因素。 目前Rosnilimab治疗RA的12周数据已经取得了突破性成功，期待28周的临床结果能继续保持优异的疗效和安全性，以及能够在UC上适应症同样取得进展。 竞争格局方面，目前全球范围内处于临床阶段的PD-1激动剂并不多。强生在礼来Peresolimab登顶NEJM后，就把JNJ-4703推进了治疗特应性皮炎的2期临床，另外吉利德和BI也进行了相应的布局。 值得一提的是，金赛药业也布局了PD-1激动剂，近期密集取得了成人系统性红斑狼疮、成人原发性干燥综合征、炎症性肠病和类风湿关节炎四个自身免疫病的临床批件，值得期待。 02 PD-L1 ADC， 辉瑞带头，国内复宏汉霖、映恩领先 AnaptysBio旗下PD-1激动剂的阶段性成功，有望成为PD-1激动剂踏入自免领域的关键突破口。 回到肿瘤领域来看，近期PD-L1 ADC的进展，也有望使得PD-L1靶点在肿瘤领域取得下一阶段的成功。 bioSeedin此前相关报道：PD-L1 ADC：辉瑞挺进3期，复宏汉霖、映恩生物奋勇直追 辉瑞在2024年财报表明，将在2025年下半年启动PF-08046054一线治疗mHNSCC和二线治疗NSCLC的两项关键3期临床研究。 辉瑞选择迅速推进PF-08046054的原因或许是基于在2024 ESMO上公布的临床数据，结果显示，82名患者在最高剂量1.75 mg/kg下的ORR为25%。在头颈部和非小细胞肺癌患者中，研究者评估的这些剂量的ORR分别为16%和22%。 辉瑞的PF-08046054挺进临床3期，也意味着PD-L1 ADC赛道或许已经到了真正爆发的前夕。 在全球竞争格局方面，目前除了辉瑞之外，处于临床阶段的PD-L1 ADC均由国内药企开发，分别是来自复宏汉霖的HLX43以及映恩生物的DB-1419。 复宏汉霖的HLX43是全球第二款进入临床阶段的PD-L1 ADC。近期，复宏汉霖密集启动了HLX43的3项临床2期研究，分别探索HLX43单药治疗肝细胞癌、食管鳞状细胞癌以及宫颈癌患者的潜力，来势汹汹。 并且，“IO+ADC”的大趋势下，复宏汉霖也在探索PD-L1 ADC与PD-1单抗联用的潜力。1月10日，复宏汉霖宣布HLX43联合PD-1单抗H药治疗晚期/转移性实体瘤患者的Ib/II期临床试验申请已获得中国NMPA批准。 映恩生物的DB-1419是映恩首款进入临床阶段的双抗ADC，同样也是全球首款同时靶向PD-L1和B7H3的ADC。 目前DB-1419已经在中国、美国和澳大利亚获批临床研究，临床1/2期试验DB-1419-O-1001研究已经在2024年9月完成了首例患者给药。 除了映恩生物布局了PD-L1/B7H3双抗ADC外，康源久远和博奥信同样也在探索PD-L1与其他靶点组合的双抗ADC。 在AACR 2024上，康源久远分享了CD47/PD-L1双抗ADC JY207b的临床前数据。数据显示，JY207b采用30k PEG-MMAE作为linker-payload，在体外和体内模型中均展现出了良好的抗肿瘤活性。 博奥信则分享了可以用于ADC开发的HER2/PD-L1双抗BSI-730的早期数据，与曲妥珠单抗相比，BSI-730显示出与HER2相当的结合活性和内吞活性。BSI-730在PD-L1结合、内吞活性，以及在PD-1/PD-L1阻断方面等方面都显示与亲本抗PD-L1抗体相当的生物活性。 综上来看，PD-(L)1靶点经过多年探索，在ADC、激动剂领域仍然是“历久弥新”。 摆脱内卷最好的方式就是差异化，而这也是过去几年国内PD-1药企在全力探索的方向。 公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！ 公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。